Search

Introduction: Personal statements can be decisive in Canadian residency applications. With the rise in AI technology, ethical concerns regarding authenticity and originality become more pressing. This study explores the capability of ChatGPT in producing personal statements for plastic surgery residency that match the quality of statements written by successful applicants. Methods: ChatGPT was utilized to generate a cohort of personal statements for CaRMS (Canadian Residency Matching Service) to compare with previously successful Plastic Surgery applications. Each AI-generated and human-written statement was randomized and anonymized prior to assessment. Two retired members of the plastic surgery residency selection committee from the University of British Columbia, evaluated these on a 0 to 10 scale and provided a binary response judging whether each statement was AI or human written. Statistical analysis included Welch 2-sample t tests and Cohen's Kappa for agreement. Results: Twenty-two personal statements (11 AI-generated by ChatGPT and 11 human-written) were evaluated. The overall mean scores were 7.48 (SD 0.932) and 7.68 (SD 0.716), respectively, with no significant difference between AI and human groups ( P  = .4129). The average accuracy in distinguishing between human and AI letters was 65.9%. The Cohen's Kappa value was 0.374. Conclusions: ChatGPT can generate personal statements for plastic surgery residency applications with quality indistinguishable from human-written counterparts, as evidenced by the lack of significant scoring difference and moderate accuracy in discrimination by experienced surgeons. These findings highlight the evolving role of AI and the need for updated evaluative criteria or guidelines in the residency application process., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2024 The Author(s).)

Introduction: Failure of alloplastic breast reconstruction is an uncommon occurrence that may result in abandonment of reconstructive efforts or salvage with conversion to autologous reconstruction. The purpose of this study was to identify factors that predict failure of alloplastic breast reconstruction and conversion to autologous reconstruction. Methods: A retrospective chart review was conducted of patients who underwent mastectomy and immediate alloplastic breast reconstruction between 2008 and 2019. Inclusion criteria included patients 18 years or older who underwent initial alloplastic reconstruction with a minimum of 3-year follow-up. Data collected included age, body mass index, cancer type, surgical characteristics, neo/adjuvant treatment details, and complications. Results were analyzed using Fischer's exact test, t -test, and multivariate logistic regression. Results: A total of 234 patients met inclusion criteria. Of those, 23 (9.8%) required conversion from alloplastic to autologous reconstruction. Converted patients had a mean age of 50.1 ± 8.5. The time from initial alloplastic reconstruction to conversion was 30.7 months. The most common reasons for conversion included soft tissue deficiency (48%), infection (30%), and capsular contracture (22%). Patients were converted to deep inferior epigastric perforator flap (DIEP; 52%), latissimus dorsi flap with implant (26%), and DIEP with implant (22%). Multivariate logistic regression modeling identified radiation (OR 8.4 [CI = 1.7-40.1]) and periprosthetic infection (OR 14.6 [CI = 3.4-63.8]) as predictors for conversion. Conclusions: Among patients undergoing mastectomy with immediate alloplastic breast reconstruction, those treated with radiation have 8.4 greater odds of conversion and those with a periprosthetic infection have 14.6 greater odds for conversion to an autologous reconstruction., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2022 The Author(s).)

Background: The recall of Allergan Biocell (Irvine, CA) devices due to the association between anaplastic large cell lymphoma (ALCL) and macrotextured breast implants means that plastic surgeons are faced with the challenge of caring for patients with these implants in situ. Cosmetic and reconstructive surgeons have been contacting affected patients to encourage them to follow up and discuss the most appropriate risk-reduction strategies., Objectives: The aim of this study was to evaluate patient concerns about the risk of breast implant-associated ALCL (BIA-ALCL) and to compare management differences between cosmetic and reconstructive patients., Methods: A retrospective review was performed of 432 patients with macrotextured implants who presented to clinic after being contacted (121 reconstructive and 311 cosmetic). These records were analyzed for their presenting concerns, surgery wait times, and management plans. Statistical analysis was performed to compare the cohorts, and odds ratios (ORs) were computed to determine the association between patient concerns and their choice of management., Results: After consultation, 59.5% of the reconstructive cohort and 49.5% of the cosmetic cohort scheduled implant removal or exchange. The reconstructive population had a higher rate of ALCL concern (62.7%); however, both cohorts had a significant OR, demonstrating an expressed fear of ALCL likely contributed to their subsequent clinical management (OR cosmetic, 1.66; OR reconstructive, 2.17)., Conclusions: Although the risk of ALCL appears to be more concerning to the reconstructive population, both cohorts were equally motivated to have their implants removed. Informing patients about their ALCL risk is crucial to ensure a patient-supported risk reduction plan., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Aesthetic Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We present measurements of the outdoor stability of PCDTBT:PC71BM based bulk heterojunction organic solar cells for over the course of a year. We find that the devices undergo a burn-in process lasting 450 hours followed by a TS80 lifetime of up to 6200 hours. We conclude that in the most stable devices, the observed TS80 lifetime is limited by thermally-induced stress between the device layers, as well as materials degradation as a result of edge-ingress of water or moisture through the encapsulation.

Background: Mastectomy flap necrosis is a common complication of immediate breast reconstruction that impacts recovery time and reconstructive success. Nitroglycerin ointment is a topical vasodilator that has been shown to improve skin flap survival in an animal model. The objective of this study was to evaluate whether the application of nitroglycerin ointment to the breast skin after mastectomy and immediate reconstruction causes a decrease in the rate of mastectomy flap necrosis compared with placebo., Methods: This study was conducted as a randomized controlled trial and included patients aged 21 to 69 years undergoing mastectomy and immediate breast reconstruction at the University of British Columbia-affiliated hospitals (Vancouver, British Columbia, Canada). Patients with a medical history that precluded the administration of nitroglycerin were excluded from the study. The target sample size was 400 patients. Nitroglycerin ointment (45 mg) or a placebo was applied to the mastectomy skin at the time of surgical dressing., Results: The trial was stopped at the first interim analysis after 165 patients had been randomized (85 to the treatment group and 80 to the placebo group). Mastectomy flap necrosis developed in 27 patients (33.8 percent) receiving placebo and in 13 patients (15.3 percent) receiving nitroglycerin ointment; the between-group difference was 18.5 percent (p = 0.006; 95 percent CI, 5.3 to 31.0 percent). Postoperative complications were similar in both groups [nitroglycerin, 22.4 percent (19 of 85); placebo, 28.8 percent (23 of 80)]., Conclusions: In patients undergoing mastectomy and immediate reconstruction, there was a marked reduction in mastectomy flap necrosis in patients who received nitroglycerin ointment. Nitroglycerin ointment application is a simple, safe, and effective way to help prevent mastectomy flap necrosis., Clinical Question/level of Evidence: Therapeutic, I.

Background: Direct-to-implant single-stage immediate breast reconstruction using acellular dermal matrix is a cost-effective alternative to two-stage expander-implant reconstruction. The purpose of this study was to identify predictors of direct-to-implant single-stage immediate breast reconstruction failure, defined as need for early (≤6 months) revision surgery., Methods: The authors conducted a retrospective cohort study of all patients with direct-to-implant single-stage immediate breast reconstruction in 2010 and 2011 at three University of British Columbia hospitals. Data were compared between successful and failed single-stage reconstructions. Predictors of failure were identified using multivariate logistic regression. Patient demographics and complications were compared to a random sample of control patients with two-stage alloplastic reconstruction without acellular dermal matrix., Results: Of 164 breasts that underwent direct-to-implant single-stage immediate breast reconstruction, 52 (31.7 percent) required early revision. Increasing breast cup size was the only significant predictor of early revision compared with bra size A (OR for bra size B, 4.86; C, 4.96; D, 6.01; p < 0.05). Prophylactic mastectomies showed a trend toward successful single stage (OR, 0.47; p = 0.061), whereas smoking history trended toward failure (OR, 1.79; p = 0.065). Mastectomy flap necrosis was significantly higher in direct-to-implant single-stage immediate reconstruction cases compared to two-stage controls., Conclusions: Direct-to-implant breast reconstruction can be reliably performed in a single stage in patients with small breast size. Increasing breast cup size confers a higher chance of early revision. A two-stage approach may be more cost-effective in larger breasted patients., Clinical Question/level of Evidence: Risk, III.

Objective: We sought to identify changes in four-and-a-half LIM-protein 2 levels and location in human cardiomyocytes during the transition from compensated aortic stenosis to left ventricular failure. We also sought to characterize four-and-a-half LIM-protein 2 binding with the metabolic enzymes phosphofructokinase 2, adenylate kinase, and creatine kinase M isoform during this transition and their consequential subcellular localization in failing human ventricles., Methods: Left ventricular biopsy specimens from selected patients undergoing aortic valve replacement for aortic stenosis were allocated to one of 2 groups: (1) nondilated with preserved left ventricular function (nonfailing group, n = 16) and (2) grossly dilated with poor left ventricular function (failing group, n = 15). These were compared with a control group of unused donor hearts (n = 6). Protein levels and subcellular localization were determined by means of Western blotting and immunofluorescence. Four-and-a-half LIM-protein 2 binding to adenylate kinase, creatine kinase M isoform, or phosphofructokinase 2 was studied by means of coimmunoprecipitation. Phosphofructokinase 2, adenylate kinase, and creatine kinase M isoform activities were assayed in protein extractions., Results: Four-and-a-half LIM-protein 2 levels were preserved in nonfailing hypertrophied hearts but reduced by 53% in failing hearts. The pattern of four-and-a-half LIM-protein 2 staining was disrupted in failing hearts: four-and-a-half LIM-protein 2 was lost from the sarcomere but present in the perinuclear Golgi apparatus complex. Phosphofructokinase 2, adenylate kinase, and creatine kinase M isoform coimmunoprecipitated in vitro and colocalized with four-and-a-half LIM-protein 2 in both hypertrophied and failing hearts. Phosphofructokinase 2 and adenylate kinase activities were reduced to 77% and 58% of normal values in compensated aortic stenosis, with phosphofructokinase 2 activity decreased further to 56% of normal value in failing hearts, but creatine kinase activity remained unchanged., Conclusions: Altered four-and-a-half LIM-protein 2 expression in heart failure is associated with disruption of the normal subcellular localization of phosphofructokinase 2, adenylate kinase, and creatine kinase M isoform and reduced activity of phosphofructokinase 2 and adenylate kinase, which might have important consequences for myocardial energy metabolism in heart failure.

Over the past two decades, topical negative pressure (TNP) wound therapy has gained wide acceptance as a genuine strategy in the treatment algorithm for a wide variety of acute and chronic wounds. Although extensive experimental and clinical evidence exists to support its use and despite the recent emergence of randomised control trials, its role and indications have yet to be fully determined. This article provides a qualitative overview of the published literature appertaining to the use of TNP therapy in the management of acute wounds by an international panel of experts using standard methods of appraisal. Particular focus is applied to the use of TNP for the open abdomen, sternal wounds, lower limb trauma, burns and tissue coverage with grafts and dermal substitutes. We provide evidence-based recommendations for indications and techniques in TNP wound therapy and, where studies are insufficient, consensus on best practice.

Objective: We identified changes in Jumonji (JARID2) expression in failing human hearts and determined its effects on expressions of atrial natriuretic factor (ANF), myosin light chain 2a (MLC2A), and alpha myosin heavy chain (MHCA), genes associated with both human heart failure and the fetal gene program., Methods: Left ventricular outflow tract cardiac biopsy samples were taken from 31 patients with aortic valvular stenosis. Hearts were grouped according to left ventricular size and function: nonfailing hearts (undilated with good function) and failing hearts (dilated with poor function). Protein levels were determined by Western blotting, and messenger RNA transcript levels by ratiometric reverse transcriptase-polymerase chain reaction. Luciferase assays in HL-2 cells were used to assess effects of Jarid2 on Anf, Mlc2a, and Mhca transcriptions. Chromatin immunoprecipitation was used to detect interaction of JARID2 with specific target-gene promoters., Results: JARID2 and MHCA expressions were reduced in failing hearts, whereas MLC2A and ANF were increased. In HL-2 cell culture, Jarid2 suppressed Anf and Mlc2a but enhanced Mhca. Jarid2 expression was reduced by cyclic mechanical stress, with concomitant increased Anf and Mlc2a and decreased Mhca expressions, reproducing the expression profile found in decompensated human pressure overload., Conclusion: Jumonji expression is reduced by mechanical stress in human heart failure from aortic stenosis. JARID2 regulates ANF, MLC2A, and MHCA transcription and contributes to reexpression of the fetal gene program in decompensated aortic stenosis. JARID2 appears important in transcriptional regulation of fetal genes and may emerge as a diagnostic marker for left ventricular decompensation in aortic stenosis.

It is expected that the role of the clinical pathologist will evolve from the more passive role of managing testing facilities to one of active service provider, using powerful molecular, cell biologic, and biochemical tools. The scope of knowledge required to be an effective physician scientist or an accomplished practicing clinical pathologist, however, cannot be acquired through clinical training alone and requires dedicated, structured research learning time. The goal of this article is to consider mechanisms that effectively integrate research training and scholarly activity into residency education in laboratory medicine/clinical pathology. The proposed curricula are purposely unstructured to allow maximum flexibility for training programs to meet the needs and career goals of individual residents.

Ten years have passed since the Graylyn Conference Report on Laboratory Medicine Clinical Pathology training was issued. Over that period, the Accreditation Council for Graduate Medical Education substantially revised the requirements for training programs; the American Board of Pathology amended both the requirements and the periods needed for certification; and the discipline itself, along with the broader discipline of pathology, evolved significantly. Recently, a curriculum proposal in anatomical pathology was published as a potential template to be used by training programs to help meet these new and evolving needs. Toward the same end, the Academy of Clinical Laboratory Physicians and Scientists has now developed a template for a curriculum in clinical pathology (laboratory medicine), taking into account newly designated and revised areas of residency core competency, the alterations in training requirements promulgated by the Accreditation Council for Graduate Medical Education and American Board of Pathology, and the rapidly developing nature of the discipline itself. The proposed clinical pathology curriculum defines goals and objectives for training, provides guidelines for instructional methods, and gives examples of how outcomes can be assessed. This curriculum is presented as a potentially helpful outline for use by pathology residency training programs.

Quality of life (QOL) can be defined as the functional effect of an illness and its consequent therapy upon a patient, as perceived by the patient. Studies on the impact of chronic venous disease on quality of life are scarce compared to quality of life research in other diseases. The purpose of this paper was to describe instruments that assess the quality of life in patients with chronic venous disease and to review the literature on this topic. A computer search of the MedLine database was performed to identify papers; the bibliographies of relevant articles were reviewed to obtain additional papers. Papers were included if they described the development or use of a quality of life instrument for patients with chronic venous disease. A total of 25 papers were identified that fit the inclusion criteria. The studies described in the papers used six different generic instruments and ten disease-specific instruments. Quality of life in chronic venous disease was assessed in 12 studies. Six studies compared different types of treatment for chronic venous disease where QOL was an outcome measure. Despite the wide variety of measures used, results indicate that the quality of life of patients with chronic venous disease is affected in the physical domain mostly with regard to pain, physical functioning and mobility, and that they suffer from negative emotional reactions and social isolation. We feel that QOL should be a standard measure in future studies in patients with chronic venous disease, preferably with a combination of generic and disease-specific measures.

Study Objective: To determine whether urinary 11-dehydrothromboxane B2 (d-TXB2) is a marker of aspirin resistance and define the relationship between aspirin dosage and concentrations of this thromboxane metabolite., Design: Randomized, crossover study., Setting: Two outpatient clinical centers., Patients: Forty-eight patients (mean age 70 yrs) with vascular disease (52% clinical coronary artery disease, 29% cerebrovascular disease, 46% atrial fibrillation)., Intervention: Levels of serum thromboxane B2 and d-TXB2 were measured after patients were treated initially with aspirin 325 mg/day for 4 weeks, then again after random assignment to receive aspirin 81, 325, or 1300 mg/day for 4 weeks, and then again after resumption of 325 mg/day for 4 weeks., Measurements and Main Results: During treatment with aspirin 325 mg/day, the mean +/- SD serum thromboxane B2 level was 0.9 +/- 1.2 ng/ml and median (interquartile range) was 0.4 (0.2-0.9) ng/ml. Mean urinary d-TXB2 was 16 +/- 7.9 ng/mmol creatinine, with a median of 15 (9.9-23) ng/mmol creatinine with aspirin 325 mg/day. After 4 weeks of aspirin 81 mg/day, levels of serum thromboxane B2 (p<0.01) and urinary d-TXB2 (p=0.04) were both significantly higher compared with aspirin 325 mg/day; for urinary d-TXB2, the median increase was 3.0 ng/mmol creatinine. After 4 weeks of treatment with aspirin 1300 mg/day, levels of serum thromboxane B2 (p<0.01) and urinary d-TXB2 (p<0.01) were both significantly lower compared with aspirin 325 mg/day; the median decrease in urinary d-TXB2 was 4.4 ng/mmol creatinine., Conclusion: Different aspirin dosages significantly affect serum and urinary markers of thromboxane synthesis.

Reactive hyperaemia (RH) following brief ischaemia is reduced in hypertrophied hearts, and this may contribute to reduced coronary flow reserve. We studied vasodilatation during RH and in response to exogenous stimuli in control and hypertrophied hearts and explored the mechanisms underlying RH. Vascular reactivity was assessed in isolated hypertrophied hearts (55+/-3 days after aortic banding or sham operation) by constructing dose-response curves to acetylcholine (ACh), sodium nitroprusside (SNP) and adenosine. Reactive hyperaemic vasodilatation was assessed after global ischaemia (5-120 s) in the presence/absence of L -NAME, 8-phenyltheophylline (8-PT) and glibenclamide. Purine release and NO overflow in the coronary perfusate were analysed. Aortic constriction increased heart/body weight ratio (47%), myocyte size (19%) and arteriolar wall thickness (51%), all P<0.01. Coronary reserve was reduced in hypertrophy (105+/-8%v 182+/-12%, P<0.01). Dose response curves for ACh, SNP and adenosine were reduced in hypertrophy (69%, 86% and 68%, all P<0.01) v shams; however ED(50)values were unchanged. The peak flow and duration of RH were also attenuated (50%, P<0.001) in hypertrophy. While purine washout during RH was related to the duration of preceding ischaemia, nitrate washout was not. RH experiments in the presence of L -NAME, 8-PT and glibenclamide indicated that RH is mediated by combined actions of K(ATP)channels>adenosine>NO in both groups. RH is mediated by similar mechanisms in control and hypertrophied hearts. All vasodilatation was similarly attenuated in hypertrophy, independent of endothelial activation. We hypothesize that increased arteriolar wall thickness may limit vasodilator responses to all stimuli in hypertrophy., (Copyright 2000 Academic Press.)

Background: Risk factors for myocardial infarction (MI) have not been well characterized in older adults, and in estimating risk, we sought to assess the individual and joint contributions made by both traditional risk factors and measures of subclinical disease., Methods: In the Cardiovascular Health Study, we recruited 5888 adults aged 65 years and older from 4 US centers. At baseline in 1989-1990, participants underwent an extensive examination that included traditional risk factors such as blood pressure and fasting glucose level and measures of subclinical disease as assessed by electrocardiography, carotid ultrasonography, echocardiography, pulmonary function, and ankle-arm index. Participants were followed up with semiannual contacts, and all cardiovascular events were classified by the Morbidity and Mortality Committee. The main analytic technique was the Cox proportional hazards model., Results: At baseline, 1967 men and 2979 women had no history of an MI. After follow-up for an average of 4.8 years, there were 302 coronary events, which included 263 patients with MI and 39 with definite fatal coronary disease. The incidence was higher in men (20.7 per 1000 person-years) than women (7.9 per 1000 person-years). In all subjects, the incidence was strongly associated with age, increasing from 7.8 per 1000 person-years in subjects aged 65 to 69 years to 25.6 per 1000 person-years in subjects aged 85 years and older. Glucose level and systolic blood pressure were associated with the incidence of MI, but smoking and lipid measures were not. After adjustment for age and sex, the significant subclinical disease predictors of MI were borderline or abnormal ejection fraction by echocardiography, high levels of intimal-medial thickness of the internal carotid artery, and a low ankle-arm index. Forced vital capacity and electrocardiographic left ventricular mass did not enter the stepwise model. Excluding subjects with clinical cardiovascular diseases such as prior angina or congestive heart failure at baseline had little effect on these results. Risk factors were generally similar in men and women., Conclusions: After follow-up of 4.8 years, systolic blood pressure, fasting glucose level, and selected subclinical disease measures were important predictors of the incidence of MI in older adults. Uncontrolled high blood pressure may explain about one quarter of the coronary events in this population.

Purpose: To determine adherence with practice guidelines in a population-based cohort of elderly persons aged 70 years or older with atrial fibrillation., Subjects and Methods: This was a cross-sectional analysis of a subgroup of participants in the Cardiovascular Health Study, a prospective observational study involving four communities in the United States. Subjects were participants with atrial fibrillation on electrocardiogram at one or more yearly examinations from 1993 to 1995. The outcome measure was self-reported use of warfarin in 1995., Results: In 1995, 172 (4.1%) participants had atrial fibrillation together with information regarding warfarin use and no preexisting indication for its use. Warfarin was used by 63 (37%) of these participants. Of the 109 participants not reporting warfarin use, 92 (84%) had at least one of the clinical risk factors (aside from age) associated with stroke in patients with atrial fibrillation. Among participants not taking warfarin, 47% were taking aspirin. Several characteristics were independently associated with warfarin use, including age [odds ratio (OR) = 0.6 per 5-year increment, 95% CI 0.5-0.9], a modified mini-mental examination score <85 points [OR = 0.3, 95% confidence interval (CI) 0.1-0.9], and among patients without prior stroke, female sex (OR = 0.5, 95% CI 0.2-1.0)., Conclusions: Despite widely publicized practice guidelines to treat patients who have atrial fibrillation with warfarin, most participants who had atrial fibrillation were at high risk for stroke but were not treated with warfarin. More studies are needed to determine why elderly patients with atrial fibrillation are not being treated with warfarin.

Because of the relatively low incidence of TEs in children, the diagnostic and therapeutic approaches used are largely extrapolated from guidelines for adults. Features that differ in children compared with adults include underlying disorders, high incidence of CVL-related DVT in the upper venous system, and response to SH, warfarin, and thrombolytic agents. There is a paucity of information on the risk/benefit ratio of the therapeutic interventions and long-term outcome. Clinical trials are urgently needed to clarify optimal management for pediatric patients with TEs.

Objective: To describe relationships between age and sub-clinical cardiovascular disease, manifest chronic disease, and physical functioning and limitations among persons aged 65 years and older, with emphasis on the "oldest old," those 85 years and older., Design: Observational population-based study., Setting: Four U.S. communities: Forsyth County, North Carolina; Sacramento County, California; Washington County, Maryland; and Pittsburgh, Pennsylvania., Participants: 5,201 men and women aged 65 years and older., Measurements: Demographic data; histories of cardiovascular disease (CVD), chronic lung disease, arthritis, diabetes, and hypertension; measures of subclinical disease including arm and ankle blood pressures, internal carotid wall thickness and stenosis, ejection fraction, left ventricular mass, fractional shortening, and diastolic function, electrocardiographic left ventricular hypertrophy and cardiac injury score, forced expiratory flow and volume; functional status including self-reported physical functioning, hearing and sight limitations and health status, and performance-based measures of function. These variables were examined among men and women in three age groups: 65-74 years, 75-84 years, and 85 + years. Subgroups of participants with and without manifest CVD were also examined., Main Results: In women, the prevalence of CVD and other chronic conditions increased with age, and the highest rates occurred among those 85 years and older. In men, prevalence rates increased between the two younger groups, but the oldest group had lower than expected rates for coronary heart disease, cerebrovascular disease, hypertension, and chronic lung disease. In contrast, there were strong age-related linear trends in most of the subclinical measures of blood pressure, atherosclerosis and pulmonary function and in virtually all measures of functional status in both gender groups across the age range. There was a particularly marked decline in functional status between the two older age groups. While subclinical disease was greater and functional status was poorer among those with manifest CVD, with few exceptions, age-related trends were not significantly different between the two groups., Conclusions: Lower than expected prevalence rates of CVD among those aged 85 years and older, particularly among men, in this study of community-dwelling elderly may represent selection bias or a real plateauing in disease prevalence with age. However, subclinical disease appears to increase and functional status to decline across the age range in both men and women regardless of the presence of CVD. The apparent increase in subclinical disease with age indicates potential for CVD prevention after age 65.

Recent laboratory studies have demonstrated that intracisternal administration of recombinant tissue plasminogen activator (rt-PA) can facilitate the normal clearing of blood from the subarachnoid space and prevent or ameliorate delayed arterial spasm. The results of a preliminary Phase I trial of intracisternal rt-PA in 10 patients are reported with documented aneurysmal subarachnoid hemorrhage (SAH). All patients enrolled were classified as clinical Grade III or IV (according to Hunt and Hess) with thick clots or layers of blood in the basal cisterns and major cerebral fissures (Fisher Grade 3). Ventriculostomy and surgery for clipping of the aneurysms were performed within 48 hours of hemorrhage. In one patient, 10 mg rt-PA was instilled into the subarachnoid cisterns prior to closing the dura. In the remaining nine patients, a small silicone catheter was left in the subarachnoid space and rt-PA (5 mg in four cases or 1.5 mg (0.5 mg every 8 hours for three infusions) in five cases) was instilled 12 to 24 hours after surgery. Minor local bleeding complications were noted in all patients receiving 5 or 10 mg rt-PA. Oozing was noted at the operative incision site in four of five patients and at the ventriculostomy site in two patients. One patient developed a small epidural hematoma that was treated by delayed drainage. No bleeding complications were noted in the patients receiving the lower regimen of rt-PA (three infusions of 0.5 mg each). Serial coagulation studies demonstrated no evidence of systemic fibrinolysis. Analysis of cisternal cerebrospinal fluid samples revealed thrombolytic tissue plasminogen activator (t-PA) levels for 24 to 48 hours. Follow-up cerebral angiography 7 to 8 days after rupture disclosed mild to moderate spasm in nine patients, while one patient with hemorrhage from a posterior inferior cerebellar artery aneurysm had severe focal spasm of the vertebral arteries that was not symptomatic. These results suggest that postoperative treatment with rt-PA may be effective in reducing the severity of delayed cerebral vasospasm. The results of serial t-PA levels suggest that the lower dosage regimen with divided dosages at 8-hour intervals is well tolerated and that even lower dosages may be effective. Further studies are clearly indicated.

In the Thrombolysis in Myocardial Infarction, Phase II pilot and clinical trial, 908 patients [326 (35.9%) in the pilot study and 582 (64.0%) in the randomized study] were treated with 150 mg recombinant tissue-type plasminogen (rt-PA) activator in combination with heparin and aspirin, and 3,016 patients [64 (2.1%) in the pilot study and 2,952 (97.9%) in the randomized study] were treated with 100 mg rt-PA in combination with heparin and aspirin. Adverse neurological events occurred in 23 patients treated with 150 mg rt-PA (2.5%) [nine cerebral infarctions (1.0%), 12 intracerebral hemorrhages (1.3%), and two subdural hematomas (0.2%)] and in 33 patients treated with 100 mg rt-PA (1.1%) [20 cerebral infarctions (0.7%), 11 intracerebral hemorrhages (0.4%), and two subdural hematomas (0.1%)]. The difference in adverse neurological events observed comparing the two rt-PA regimens was primarily due to a higher frequency of intracerebral bleeding among patients treated with 150 mg rt-PA (1.3% versus 0.4%, p less than 0.01). Patients with recent (within 6 months) histories of stroke were not eligible for the study, and patients with any history of cerebrovascular disease were declared ineligible early in the study. The small number of patients (89, or 2.3%) with any history of neurological disease, intermittent cerebral ischemic attacks, or stroke who were enrolled before the stricter eligibility criteria were imposed or on the basis of incomplete baseline information experienced an increased frequency of intracerebral hemorrhage compared with patients without such histories (3.4% versus 0.5%). Mortality at 6 weeks after presentation among 23 patients who had intracerebral hemorrhage was 47.8%. Intracerebral hemorrhage is a severe but infrequent complication of rt-PA therapy for acute myocardial infarction. The combined frequency of intracerebral hemorrhage, subdural hematoma, and cerebral infarction after treatment with 100 mg rt-PA is comparable to that observed in other trials with thrombolytic agents in acute myocardial infarction.

Thrombolytic therapy is rapidly becoming a routine part of the treatment of acute myocardial infarction. The clinical laboratory is often called upon to help monitor changes in the hemostatic system in these patients. This review will address laboratory monitoring of patients treated with the two most commonly used thrombolytic agents: streptokinase (SK) and recombinant tissue plasminogen activator (rt-PA). The fibrinolytic system and recent clinical trials are discussed. This is followed by a review of available assays and their place in therapeutic monitoring.

Desmoid tumors are locally invasive benign tumors arising from musculoaponeurotic structures which are classified as fibromatoses and which have generally high post-surgical recurrence rates. Sixteen patients with desmoid tumors were treated with irradiation and evaluated for 2 to 6 years post-treatment. Of the 16, 13 cases have been controlled without recurrence. Virtually complete resolution of the tumor mass has been accomplished without the disfigurement and dysfunction characteristic of the radical surgical approach to treatment.

Decreased endothelial cell production of prostacyclin (PGI2) in response to the lupus anticoagulant has been previously demonstrated and postulated to have a causal relationship to the thrombotic events associated with the lupus anticoagulant. Five patients who exhibited the anticoagulant were studied in an effort to determine if a relationship exists between exposure of endothelial cells to the lupus anticoagulant and decreased production of PGI2. Human endothelial cells derived from human umbilical vein grown in culture were exposed to IgG fractions of patient plasmas containing the lupus anticoagulant. PGI2 released per 10(6) cells was determined by radioimmunoassay for 6-keto-PGF-1-alpha. The overall means for the patient and control groups are given by 47 pM/10(6) cells and 12 pM/10(6) cells respectively. This is a statistically significant difference (F = 10.65, p = 0.017) when the effects of different batches of endothelial cells and thrombin stimulation are adjusted for in the analysis of variance model. These results demonstrate that in this homologous human system exposure of endothelial cells to the lupus anticoagulant leads to stimulation rather than inhibition of PGI2 release.