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BackgroundLanadelumab demonstrated efficacy in preventing hereditary angioedema (HAE) attacks in the phase 3 HELP Study.ObjectiveTo assess time to onset of effect and long-term efficacy of lanadelumab, based on exploratory findings from the HELP Study.MethodsEligible patients with HAE type I/II received lanadelumab 150 mg every 4 weeks (q4wks), 300 mg q4wks, 300 mg q2wks, or placebo. Ad hoc analyses evaluated day 0-69 findings using a Poisson regression model accounting for overdispersion. Least-squares mean monthly HAE attack rate for lanadelumab was compared with placebo. Intrapatient comparisons for days 0-69 versus steady state (days 70-182) used a paired t test for continuous endpoints or Kappa statistics for categorical endpoints.ResultsOne hundred twenty-five patients were randomized and treated. During days 0-69, mean monthly attack rate was significantly lower with lanadelumab (0.41-0.76) vs placebo (2.04), including attacks requiring acute treatment (0.33-0.61 vs 1.66) and moderate/severe attacks (0.31-0.48 vs 1.33, all P ≤ .001). More patients receiving lanadelumab vs placebo were attack free (37.9%-48.1% vs 7.3%) and responders (85.7%-100% vs 26.8%). During steady state, the efficacy of lanadelumab vs placebo was similar or improved vs days 0-69. Intrapatient differences were significant with lanadelumab 300 mg q4wks for select outcomes. Lanadelumab efficacy was durable-HAE attack rate was consistently lower vs placebo, from the first 2 weeks of treatment through study end. Treatment emergent adverse events were comparable during days 0-69 and 70-182.ConclusionProtection with lanadelumab started from the first dose and continued throughout the entire study period.

The presence of both of the testes in one scrotal sac is one of the very rare presentations of testicular ectopia, which is known as transverse testicular ectopia (TTE) and is also known as crossed testicular ectopia. The presence of the uterus and fallopian tubes in a normally virilized male is termed as persistent Müllerian duct syndrome (PMDS). We report a case of an adult male who had a unique combination of both TTE and PMDS presenting as an incarcerated inguinal hernia. [ABSTRACT FROM AUTHOR]

Bicuspid aortic valve (BAV) is a common congenital valvular malformation, which may lead to early aortic valve disease and bicuspid-associated aortopathy. A novel BAV classification system was recently proposed to coincide with transcatheter aortic valve replacement being increasingly considered in younger patients with symptomatic BAV, with good clinical results, yet without randomized trial evidence. Procedural technique, along with clinical outcomes, have considerably improved in BAV patients compared with tricuspid aortic stenosis patients undergoing transcatheter aortic valve replacement. The present review summarizes the novel BAV classification systems and examines contemporary surgical and transcatheter approaches., Competing Interests: Dr Josep Rodes-Cabau has reported institutional research grants from 10.13039/100006520Edwards Lifesciences, 10.13039/100004374Medtronic, and 10.13039/100000046Abbott. Dr Michael J. Reardon has received consultation fees from Medtronic, Boston Scientific, Gore Medical, and Abbott medical paid to his department. Dr Rishi Puri is a consultant to Medtronic, Boston Scientific, Philips, Shockwave Medical, Products & Features, V-Dyne, VahatiCor, Advanced NanoTherapies, NuevoSono, TherOx, Bioventrix and Centerline Biomedical. No other disclosures were reported., (© 2023 The Author(s).)

Background: Subcutaneous human immunoglobulin (16.5%; octanorm/cutaquig ® ) was efficacious and well tolerated in patients with primary immunodeficiencies in a Phase III study. A subanalysis of pediatric data is presented here. Materials & methods: Children (2-16 years) previously treated with intravenous human immunoglobulin received weekly subcutaneous human immunoglobulin infusions over 64 weeks. The main objective was to assess the efficacy of cutaquig in preventing serious bacterial infections. Results:  38 children received 2213 infusions of cutaquig. No serious bacterial infections developed during the study. The rate of other infections was 3.1 per person-year and the rate of adverse drug reactions was 0.083 per infusion. Higher immunoglobulin G trough levels were achieved with cutaquig compared with previous intravenous therapy. Conclusion: Once-weekly infusions of cutaquig were efficacious and well tolerated in children with primary immunodeficiencies.

Importance: Current treatments for long-term prophylaxis in hereditary angioedema have limitations., Objective: To assess the efficacy of lanadelumab, a fully human monoclonal antibody that selectively inhibits active plasma kallikrein, in preventing hereditary angioedema attacks., Design, Setting, and Participants: Phase 3, randomized, double-blind, parallel-group, placebo-controlled trial conducted at 41 sites in Canada, Europe, Jordan, and the United States. Patients were randomized between March 3, 2016, and September 9, 2016; last day of follow-up was April 13, 2017. Randomization was 2:1 lanadelumab to placebo; patients assigned to lanadelumab were further randomized 1:1:1 to 1 of the 3 dose regimens. Patients 12 years or older with hereditary angioedema type I or II underwent a 4-week run-in period and those with 1 or more hereditary angioedema attacks during run-in were randomized., Interventions: Twenty-six-week treatment with subcutaneous lanadelumab 150 mg every 4 weeks (n = 28), 300 mg every 4 weeks (n = 29), 300 mg every 2 weeks (n = 27), or placebo (n = 41). All patients received injections every 2 weeks, with those in the every-4-week group receiving placebo in between active treatments., Main Outcome and Measures: Primary efficacy end point was the number of investigator-confirmed attacks of hereditary angioedema over the treatment period., Results: Among 125 patients randomized (mean age, 40.7 years [SD, 14.7 years]; 88 females [70.4%]; 113 white [90.4%]), 113 (90.4%) completed the study. During the run-in period, the mean number of hereditary angioedema attacks per month in the placebo group was 4.0; for the lanadelumab groups, 3.2 for the every-4-week 150-mg group; 3.7 for the every-4-week 300-mg group; and 3.5 for the every-2-week 300-mg group. During the treatment period, the mean number of attacks per month for the placebo group was 1.97; for the lanadelumab groups, 0.48 for the every-4-week 150-mg group; 0.53 for the every-4-week 300-mg group; and 0.26 for the every-2-week 300-mg group. Compared with placebo, the mean differences in the attack rate per month were -1.49 (95% CI, -1.90 to -1.08; P < .001); -1.44 (95% CI, -1.84 to -1.04; P < .001); and -1.71 (95% CI, -2.09 to -1.33; P < .001). The most commonly occurring adverse events with greater frequency in the lanadelumab treatment groups were injection site reactions (34.1% placebo, 52.4% lanadelumab) and dizziness (0% placebo, 6.0% lanadelumab)., Conclusions and Relevance: Among patients with hereditary angioedema type I or II, treatment with subcutaneous lanadelumab for 26 weeks significantly reduced the attack rate compared with placebo. These findings support the use of lanadelumab as a prophylactic therapy for hereditary angioedema. Further research is needed to determine long-term safety and efficacy., Trial Registration: EudraCT Identifier: 2015-003943-20; ClinicalTrials.gov Identifier: NCT02586805.

Objectives: Considering the good immediate results reported for transcatheter aortic valve implantation in high-risk patients, the role of conventional aortic valve replacement (AVR) is being questioned, especially in elderly patients. The aim of this study was to evaluate our long-term results of conventional AVR in octogenarians., Methods: A total of 2005 patients aged ≥80 years underwent AVR for aortic stenosis in our institution between 1978 and 2011. Of these, 1009 (50%) patients had an associated extracardiac comorbidity and 650 (32%) patients had coronary lesions. Valve replacement was the sole procedure in 1515 (76%) patients, and 396 (19%) patients had concomitant coronary artery bypass grafting. Data were collected at the time of surgery in our database, and regularly updated by mailed questionnaires and telephone contact., Results: Early mortality of isolated AVR was 5.5% for the last 10 years of the series. Significant risk factors were chronic obstructive pulmonary disease, chronic renal failure, advanced cardiac disease [left or right ventricular failure, New York Heart Association (NYHA) Class IV and atrial fibrillation] and coronary disease. Long-term follow-up was 99.5% complete (9 patients lost to follow-up), totalling 8849 patient-years. Nine hundred and one patients died at late follow-up with a median survival of 7.1 years, with 7 patients becoming centenarian. Apart from older age, main late causes of death were cardiovascular (20.5%), neurological deficit (10.2%) and cancer (10.2%). Actuarial survival was 83%, 62.5% and 25% at 2, 5 and 10 years, respectively. This survival compares favourably with that of a French-matched population. Above all, 90% of late survivors reported functional improvement. Univariable and multivariable analysis identified risk factors of late death as male gender, associated comorbidity, renal failure, advanced cardiac disease, atrial fibrillation and impaired ventricular function. Coronary lesions, associated cardiac surgery and small diameter prostheses (19 or 21 mm) did not impair long-term survival., Conclusions: AVR is effective for all age groups to treat aortic stenosis. Elderly people should not be denied surgery only because of their old age as conventional AVR provides an excellent quality of life and restores life expectancy. Percutaneous valve implantation is to be considered, in cases of non-operable or high-risk patients. However, to date, open-heart surgery remains the treatment of choice for aortic stenosis for the majority of patients.

Single-stage repair of complex cardiac abnormalities in high-risk neonates presents formidable challenges. The majority of hybrid strategies involving bilateral pulmonary artery banding (bPAB) with or without patent ductus arteriosus (PDA) stenting is described in the setting of hypoplastic left heart syndrome. We present a series of cases describing two-stage repair with initial palliative hybrid procedures involving bPAB with or without PDA stenting. This allows weight gain and stabilization of circulation before complete repair, provides good results, and may overcome risk factors associated with single-stage repair in neonates., (© 2018 Wiley Periodicals, Inc.)

The use of internal mammary artery (IMA) grafts for coronary artery bypass may devascularize the sternum. We performed a literature review by searching the PubMed database for studies that assessed sternal perfusion after IMA harvesting. The majority of papers describe various techniques and compared (1) IMA harvest versus no IMA harvest, (2) single versus bilateral, and (3) skeletonized versus pedicled. Evidence is inconclusive as to whether single harvesting causes significant devascularisation and whether this is increased with bilateral harvesting. Sternal ischemia may also be a transient phenomenon. However, skeletonization may preserve perfusion more than pedicled harvesting, particularly in diabetic patients., (Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Hereditary angioedema (HAE) due to C1 inhibitor deficiency manifests as recurrent swelling attacks that can be disabling and sometimes fatal. Long-term prophylaxis with twice-weekly intravenous injections of plasma-derived C1-inhibitor (pdC1-INH) has been established as an effective treatment. Subcutaneous (SC) administration of pdC1-INH has not been studied in patients with HAE., Methods: This open-label, dose-ranging, crossover study (COMPACT Phase II) was conducted in 18 patients with type I or II HAE who received two of twice-weekly 1500, 3000, or 6000 IU SC doses of highly concentrated volume-reduced CSL830 for 4 weeks each. The mean trough plasma levels of C1-INH functional activity, C1-INH and C4 antigen levels during Week 4, and overall safety and tolerability were evaluated. The primary outcome was model-derived steady-state trough C1-INH functional activity., Results: After SC CSL830 administration, a dose-dependent increase in trough functional C1-INH activity was observed. C1-INH and C4 levels both increased. The two highest dose groups (3000 and 6000 IU) achieved constant C1-INH activity levels above 40% values, a threshold that was assumed to provide clinical protection against angioedema attacks. Compared with intravenous injection, pdC1-INH SC injection with CSL830 showed a lower peak-to-trough ratio and more consistent exposures. All doses were well tolerated. Mild-to-moderate local site reactions were noted with pain and swelling being the most common adverse event., Conclusions: Subcutaneous volume-reduced CSL830 was well tolerated and led to a dose-dependent increase in physiologically relevant functional C1-INH plasma levels. A clinical outcome study of SC CSL830 in patients with HAE warrants further investigation., (© 2015 The Authors. Allergy Published by John Wiley & Sons Ltd.)

Background: External stents inhibit saphenous vein graft (SVG) intimal hyperplasia in animal studies. We investigated whether external stenting inhibits SVG diffuse intimal hyperplasia 1 year after coronary artery bypass graft surgery., Methods: Thirty patients with multivessel disease undergoing coronary artery bypass graft surgery were enrolled. In addition to an internal mammary artery graft, each patient received one external stent to a single SVG randomly allocated to either the right or left coronary territories; and one or more nonstented SVG served as the control. Graft patency was confirmed at the end of surgery in all patients. The primary endpoint was SVG intimal hyperplasia (mean area) assessed by intravascular ultrasonography at 1 year. Secondary endpoints were SVG failure, ectasia (>50% initial diameter), and overall uniformity as judged by Fitzgibbon classification., Results: One-year follow-up angiography was completed in 29 patients (96.6%). All internal mammary artery grafts were patent. Overall SVG failure rates did not differ significantly between the two groups (30% stented versus 28.2% nonstented SVG, p = 0.55). The SVG mean intimal hyperplasia area, assessed in 43 SVGs, was significantly reduced in the stented group (4.37 ± 1.40 mm(2)) versus nonstented group (5.12 ± 1.35 mm(2), p = 0.04). In addition, stented SVGs demonstrated marginally significant improvement in lumen uniformity (p = 0.08) and less ectasia (6.7% versus 28.2%, p = 0.05). There was some evidence that ligation of side branches with metallic clips increased SVG failure in the stented group., Conclusions: External stenting has the potential to improve SVG lumen uniformity and reduce diffuse intimal hyperplasia 1 year after coronary artery bypass graft surgery., (Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: There is no specific International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code for chronic idiopathic urticaria or spontaneous urticaria (CIU/CSU), a skin condition characterized by hives and angioedema lasting at least 6 weeks with no known cause., Objective: To validate an ICD-9-CM-based algorithm for identification of patients with CIU/CSU and thus facilitate claims-based research., Methods: Patient records were reviewed at 4 US practices. Patients included in the study were from a random sample of those identified by their physician as having CIU/CSU or because they met the following diagnosis-based algorithm: (1) at least 2 outpatient ICD-9-CM diagnosis codes 708.1, 708.8, or 708.9 at least 6 weeks apart or (2) 1 outpatient diagnosis of 708.1, 708.8, or 708.9 and 1 diagnosis of 995.1 at least 6 weeks apart. Data collected included ICD-9-CM codes, diagnoses of urticaria and allergy-related conditions, and medication use. Sensitivity and positive predictive value were calculated. The study was approved by the Western Institutional Review Board., Results: One hundred forty-nine patient records were reviewed (mean age 41.1 years; 73.8% were women; 69.1% were white): 115 were identified with the diagnosis-based algorithm, 90 were patients with "known CIU/CSU", and 56 were in the 2 groups. The mean duration of CIU/CSU was 2.9 to 3.1 years. The 2 cohorts most frequently had diagnoses of idiopathic urticaria, unspecified urticaria, and other specified urticaria. The diagnosis-based algorithm had a positive predictive value of 90.4% and a sensitivity of 71.1%., Conclusion: The high positive predictive value suggests that patients identified using the algorithm are highly likely to have CIU/CSU. The 71.1% sensitivity suggests that most patients with CIU/CSU will be identified. The validation statistics support the use of the diagnosis-based algorithm in claims-based research, although future studies could refine the algorithm further., (Copyright © 2015 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Mediastinitis is a devastating complication of cardiac surgery. Previous studies have often observed small populations, been retrospective in design, and used a variety of definitions for mediastinitis., Aim: To identify risk factors for mediastinitis, and strategies to minimize its incidence., Methods: A prospective cohort study of 4883 adult patients who underwent cardiac surgery between October 2003 and February 2009, comparing pre- and peri-operative risk factors, microbial aetiology, requirement for re-admission, length of stay and mortality between patients with and without mediastinitis., Findings: Ninety (1.8%) patients were diagnosed with mediastinitis. Microbial aetiology was defined for 75 patients. Staphlyocococcus aureus was the most common isolate (30 episodes; 15 due to meticillin-resistant S. aureus). Univariate analysis revealed the following pre-operative factors associated with mediastinitis: age; body mass index; diabetes; modified logistic European System for Cardiac Operative Risk Evaluation score; urgent admission; and longer pre-operative stay (P < 0.05). Associated peri-operative factors were: combined coronary artery bypass grafting plus aortic valve replacement; longer aortic cross-clamp time; and longer cardiopulmonary bypass time (P < 0.005). Multi-variate analysis revealed that higher body mass index, combined coronary artery bypass grafting plus aortic valve replacement, and older age were associated with mediastinitis (P < 0.05). Mediastinitis was associated with re-admission to hospital, longer inpatient stay and reduced long-term survival (P < 0.05)., Conclusion: Mediastinitis is associated with worse short-term outcomes (re-admission, length of stay) and reduced long-term survival. Obesity is the only modifiable pre-operative risk factor for mediastinitis. It may be possible to reduce risk through pre-operative weight loss programmes before elective surgery., (Copyright © 2014 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Background: Good consultation skills help physicians to diagnose the problems of the patient more accurately, and foster a therapeutic relationship. We describe a pilot study that used role-play with peers as a method to sensitize first clinical year medical students to consultation skills Methods. Students were divided into groups of three where one acted as a doctor, the second as a patient and the third as an observer. Students were asked to perform a role-play of a prepared clinical scenario where the patient had a hidden fear of malignancy. Observations were recorded in a simplified Calgary-Cambridge consultation checklist. Students' feedback and their emotions written after the role-play were analysed and discussed. Assessment of their learning was done with an objective structured clinical examination., Results: Students' feedback revealed that they were sensitized to the importance of starting the consultation with an open question, listening to the opening statement, non-verbal., (Copyright 2014, NMJI.)

Background: Although the potential survival benefit of bilateral internal mammary artery (BIMA) grafting in comparison with single internal mammary artery (SIMA) grafting has been emphasized by many investigators, the use of BIMA is still low in clinical practice in the absence of randomized trials and long-term results. In the current study, we aimed to assess if there is a long-term survival benefit of BIMA up to 10 years after coronary bypass surgery., Methods and Results: We selected published articles comparing survival between SIMA and BIMA patients with follow-up duration of more than a mean of 9 years. We evaluated the log hazard ratio with 95% confidence interval for included studies by using a random-effects meta-analysis. Nine eligible observational studies provided 15 583 patients (8270 SIMA and 7313 BIMA) for meta-analysis. Five studies used propensity score methods for statistical adjustment, 2 with a propensity score-based patient-matching method and 3 with quintile-based stratification. A significant reduction in mortality by using BIMA was observed (hazard ratio, 0.79; 95% confidence interval, 0.75-0.84); no study showed any significantly harmful effect of BIMA on survival. Subgroups of studies using different statistical approaches-unmatched, quintile-based propensity score analysis, and propensity score-based exact patient matching-all showed the survival benefit of BIMA grafting., Conclusions: BIMA grafting appears to have better survival with up to 10 years follow-up in comparison with SIMA grafting. Long-term survival benefit of BIMA seems to continue in the second decade after surgery. An ongoing randomized trial comparing SIMA and BIMA groups will add evidence on this issue., (© 2014 American Heart Association, Inc.)

The radial artery (RA) can be used as part of an arterial revascularization strategy in coronary artery bypass grafting (CABG). It is easy to harvest and several randomized controlled trials and meta-analyses have reported superior long-term patency over saphenous vein grafts. However, the RA is not used as frequently as the saphenous vein and questions remain regarding its optimum use as a conduit. This article comprehensively appraises current evidence surrounding outcomes, patient selection, harvesting technique, intraoperative strategy, and graft spasm prophylaxis to provide a contemporary review of the use of the RA as a conduit in CABG., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Introduction: An investigational 10% liquid intravenous immunoglobulin (IVIG) was studied in 63 patients with primary immunodeficiency (PID) at 15 study sites., Methods: Patients were treated every 3 or 4 weeks with 254-1029 mg/kg/infusion of IVIG., Results: Overall, Biotest-IVIG infusions were well tolerated. The proportion of infusions that were associated with adverse events during infusion, and up to 72 h after infusion, including those unrelated to study product, was 27.7% with an upper 95% confidence limit ≤30.6%. Two serious bacterial infections (SBIs) were observed resulting in a serious bacterial infection rate of 0.035 per person per year and an upper one-sided 99% confidence limit of ≤0.136 SBI/patient/year. The number of days of work or school missed due to infection were relatively low at 2.28 days/patient/year. Two patients were hospitalized for infection producing a rate of 0.21 hospitalization days/patient/year. The IgG half-life was approximately 30 days with variation among individuals., Conclusions: Pharmacokinetic parameters of specific antibody activities were essentially the same as those of total IgG. Biotest-IVIG is safe and effective in the treatment of PID.

We investigated the expression of methyl transferase G9a and methylated histone H3-K9 in fresh human decidual/endometrial tissue of 12 normal early pregnancies and 15 unexplained recurrent spontaneous abortions (URSA). The samples were obtained through dilatation and curettage and collected as per strict inclusion-exclusion criteria. The tissue was subjected to immunohistochemical analysis (IHC), western blotting (WB) and RT-PCR analysis. The results demonstrated methyl transferase G9a to have a lower expression in abortions when compared with that in normal pregnancy (P < 0.05). The sensitivity of RT-PCR, IHC and WB were respectively 66.67, 75 and 71.43%, while specificity of the same were 66.67, 60 and 78.92%, respectively. Methylated histone H3-K9 was significantly lower (P < 0.0001) in URSA tissues than in controls. This study suggests that methylation may cause URSA and indicates the need for further work to explore the role of methylation in URSA and its possible prevention through locally acting methylating/demethylating agents.

Objective: High-risk patients with aortic stenosis are increasingly referred to specialist multidisciplinary teams (MDTs) for consideration of trans-catheter aortic valve implantation (TAVI). A subgroup of these cases is unsuitable for TAVI, and high-risk conventional aortic valve replacement (AVR) is undertaken. We have studied our outcomes in this cohort., Methods: Data prospectively collected between March 2008 and November 2009 for patients (n = 28, nine male) undergoing high-risk AVR were analysed. The mean age was 78.4 ± 9.2 years. The mean additive EuroSCORE (European System for Cardiac Operative Risk Evaluation) was 10.0 ± 3.6 and mean logistic EuroSCORE was 19.9 ± 18.8. Three patients had undergone previous coronary artery bypass grafting (CABG)., Results: The mean ejection fraction was 51 ± 16%, mean valve area 0.56 ± 0.19 cm², and mean peak gradient 91 ± 27 mm Hg. Ascending aortic, right axillary artery and femoral artery cannulation was used in 64%, 29% and 7% of cases, respectively. Median cross-clamp and cardiopulmonary bypass times were 84 (68-143) min and 111 (94-223) min. The median (range) inserted valve size was 21 (19-25) mm. Median intensive care and overall hospital stay were 5 (2-37) and 11 (5-44) days, respectively. In-hospital mortality was 4% (one patient). Postoperative complications included re-operation for bleeding (7%), renal failure (21%), tracheostomy (14%), sternal wound infection (7%), atrial fibrillation (25%) and permanent pacemaker implantation (7%). Kaplan-Meier survival at median follow-up of 359 (148-744) days was 81% (one further death of non-cardiac aetiology). Quality-of-life assessment at follow-up also yielded satisfactory results., Conclusions: MDT assessment of high-risk aortic stenosis in the era of TAVI has increased the number of referrals. Conventional open surgery remains a valid option for these patients, with acceptable in-hospital mortality and early/midterm outcomes but high in-hospital morbidity., (Copyright © 2011 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.)

We performed a systematic review of the literature to establish whether revascularisation of the left subclavian territory is necessary when this artery is covered by a stent. We retrieved data from 99 studies incorporating 4906 patients. Incidences of left-arm ischaemia (0.0% vs 9.2%, p=0.002) and stroke (4.7% vs 7.2%, p<0.001) were significantly less following revascularisation, although mortality (10.5% vs 3.4%, p=0.032) and endoleak incidence (25.8% vs 12.6%, p=0.008) were increased. No significant differences in spinal-cord ischaemia were seen. Revascularisation may reduce downstream ischaemic complications but can cause significant risk. Indications must be carefully considered on an individual patient basis., (Copyright © 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.)

Background: Despite the publication of recent guidelines for management of the left subclavian artery (LSA) during endovascular stenting procedures of the thoracic aorta, specific management for those presenting with dissection remains unclear. This systematic review attempts to address this issue., Methods: Systematic assessment of the published data on thoracic aorta dissection was performed identifying 46 studies, which incorporated 1,275 patients. Primary outcomes included the prevalence of left arm ischemia, stroke, spinal cord ischemia, endoleak, stent migration, and mortality. Outcomes were compared between patients with and without LSA coverage and revascularization incorporating factors such as the number of stents used, length of aorta covered, urgency of intervention, and type of dissection (acute or chronic). Statistical pooling techniques, χ(2) tests, and Fisher's exact testing were used for group comparisons., Results: As compared with other outcomes, LSA coverage without revascularization in the presence of aortic dissection is much more likely to be complicated by left arm ischemia (prevalence increased from 0.0% to 4.0% [p = 0.021]), stroke (prevalence increased from 1.4% to 9.0% [p = 0.009]), and endoleak (prevalence increased from 4.0% to 29.3% [p = 0.001]). However, revascularization was not shown to reverse these effects. Longer aortic coverage (≥ 150 mm) was associated with an increased prevalence of spinal cord ischemia (from 1.3% to 12.5% [p = 0.011]) and mortality (from 1.3% to 15.6% [p = 0.003])., Conclusion: In patients undergoing endovascular stenting for thoracic aortic dissection, in cases where LSA coverage is necessary, revascularization should be considered before the procedure to avoid complications such as left arm ischemia, stroke, and endoleak, and where feasible, an appropriate preoperative assessment should be carried out., (Copyright © 2010. Published by Elsevier Inc.)

Prosthetic aortic valve dysfunction presenting as aortic regurgitation is a complication of mechanical valve replacement. We describe a case of late valve dysfunction caused by an annular suture of excessive length obstructing the closure mechanism of a bileaflet prosthetic valve.We present this rare cause of valve dysfunction in an 80-year-old male patient who presented with haemolysis and dyspnoea. At the time of operation it was found that a long vertically positioned annular valve suture was interfering with the normal closure mechanism of one of the prosthetic leaflets causing eccentric regurgitation jets. These findings were misdiagnosed as paravalvular leaks on the preoperative transoesophageal echo. No paravalvular leak was identified intraoperatively. After removal of the responsible suture normal prosthetic valve function was restored.Whilst early aortic valve dysfunction caused by suture material has previously been reported, this is the first report of suture material causing late dysfunction.

Ten human monoclonal antibodies derived from peripheral B cells of a patient with human T-cell lymphotropic virus (HTLV)-associated myelopathy are described. One monoclonal antibody recognized a linear epitope within the carboxy-terminal 43 amino acids of HTLV gp21, and two monoclonal antibodies recognized linear epitopes within HTLV type 1 (HTLV-1) gp46. The remaining seven monoclonal antibodies recognized denaturation-sensitive epitopes within HTLV-1 gp46 that were expressed on the surfaces of infected cells. Two of these antibodies also bound to viable HTLV-2 infected cells and immunoprecipitated HTLV-2 gp46. Virus neutralization was determined by syncytium inhibition assays. Eight monoclonal antibodies, including all seven that recognized denaturation-sensitive epitopes within HTLV-1 gp46, possessed significant virus neutralization activity. By competitive inhibition analysis it was determined that these antibodies recognized at least four distinct conformational epitopes within HTLV-1 gp46. These findings indicate the importance of conformational epitopes within HTLV-1 gp46 in mediating a neutralizing antibody response to HTLV infection.

Human prostate carcinoma cell line DU-145 was used to examine the relationship between the intracellular levels of cysteine-rich metallothionein (MT) and the sensitivity or resistance of cells to Adriamycin (ADR). The basis for the poor response of human prostate carcinomas to ADR was studied. Cadmium-resistant (Cdr) cells, capable of growth in 10(-5) M cadmium, were derived from DU-145 cadmium-sensitive (Cds) cells, by exposure to increasing concentrations of cadmium. The relative rates of MT synthesis were measured by L-[35S]cysteine incorporation and MT separation by high-performance liquid chromatography. Cdr cells, continuously exposed to cadmium, show a steady-state rate of MT synthesis (designated as control = 100%) which is 3.5 times the basal rate in Cds cells (29%). Dose-response curves, using clonal and cell count assays, show that the dose levels required to produce inhibition of growth to 50% and 90% of control, respectively, of ADR for Cdr cells (19.00 and 132.0 ng/ml) are 1.5 to 1.7 times those for Cds cells (12.5 and 77.5 ng/ml). In the absence of cadmium, deinduction of MT occurs with MT synthesis declining, after 70 and 118 h, to 29% and 19% of control. Correspondingly, in such deinduced cells (Cdr minus cadmium), the 50% inhibitory doses of ADR in clonal and growth assays are 3.5 and 4.8 ng/ml, respectively. Thus, deinduced cells are 3 and 4 times more sensitive to ADR than Cds and Cdr cells. This increased sensitivity is explained by the rapid and marked inhibition of MT synthesis upon exposure to ADR, even in the presence of cadmium, so that after 6 and 10 h in the presence of 10 ng/ml of ADR, the rates drop to 62% and 19% of control. On the basis of these results, we propose that: (a) the increased levels of MT increase the resistance of Cdr cells to ADR and that this may be partly responsible for the poor response of prostate carcinomas to ADR; (b) MT deinduction results in increased sensitivity to ADR; and (c) ADR inhibits MT synthesis. Thus, it is suggested that a treatment regimen consisting of ADR exposure followed by a second exposure, during increased ADR sensitivity, may be effective for growth inhibition of slow-growing prostatic carcinomas.