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Background Medtronic is developing an atrial Micra Transcatheter Pacing System (Medtronic, Minneapolis, Minnesota) and associated retrieval system. Objective The purpose of this study was to evaluate chronic atrial Micra retrieval, reimplantation, and chronic pacing performance. Methods Sheep were implanted in 2 groups: group 1 (n = 6) for 6 months, a second device implanted, and first retrieved and studied for an additional 6 months; group 2 (n = 6) for 6 months, devices were retrieved, and a second device implanted and observed acutely. Both groups underwent histopathological evaluation. Pacing capture thresholds (PCTs), p wave amplitude, and pacing impedances were measured chronically. Device retrieval times were recorded, and intracardiac echocardiography was used. Results At 24 weeks, PCTs for group 1 were low and stable for both the first device (0.55 ± 0.14 V) and the second device (0.57 ± 0.09 V), in which the average retrieval time was 17:35 minutes. For group 2, the average retrieval time was 6:12 minutes, chronic PCTs in the first device were 0.53 ± 0.11 V, and acute PCTs for the second device were 0.71 ± 0.19 V. Pathological findings were within an expected range of tissue responses for similar Micra acute and chronic implants and device retrievals. p waves and impedances were stable and within an expected range for implant site and electrode design. Complications included 1 early dislodgment and 1 death attributed to a prototype retrieval tool. Conclusion In an animal model, an atrial Micra can be easily implanted with excellent chronic pacing performance and is easily retrievable at 6 months. A second device can successfully be implanted with low, chronic stable thresholds. A developed prototype retrieval tool was easy to use and, with modifications, complication free.

Background The number of lead extractions is growing because of the greater population and increasing age of individuals with a cardiac implantable electronic device. Lead extraction procedures can be complex undertakings with risk of significant mortality, and vascular tears in the superior vena cava are of greatest concern. Objective The purpose of this study was to study whether a novel algorithm that analyzes pre-extraction computed tomographic (CT) images can determine the likelihood and location of lead–lead interactions and lead–vessel attachment within patients' venous vasculatures. This information can be used to identify potential case challenges in the planning stages. Methods We developed an algorithm to estimate the presence and position of lead–lead interactions and lead–vessel adherences by tracking distance between the leads and distance between the lead and superior vena cava in a sample of 12 patients referred to the United Heart and Vascular Clinic for lead extractions due to infection (n = 5), lead failure (n = 5), and tricuspid regurgitation (n = 2). Results Preliminary results indicate that the developed algorithm successfully identified lead–lead and lead–vascular attachments compared to review of CT images by medical experts. Conclusion With future validation and clinical implementation, this algorithm could aid physician preparedness by minimizing intraprocedural emergencies and may improve patient outcomes.

BACKGROUND The INGEVITY lead (Boston Scientific, St Paul, MN, USA) has excellent clinical performance. However, its single filar design results in decreased lead tensile strength and a possible challenging extraction. This study's goal is to evaluate techniques for extracting the INGEVITY lead. METHODS Two- and three-dimensional models were created to simulate lead extraction from a right atrial appendage lead implant with a left subclavian approach and lead/fibrosis attachment sites. Standard and unique lead extraction preparation strategies were evaluated. Traction forces were measured from a superior approach alone or in combination with a femoral approach. RESULTS For lead extraction via the superior approach, leaving the terminal on the lead was the only factor influencing maximum tolerated load (p-value = .0007). Scar attachment provided greater lead tensile strength by transferring traction loading forces to the polyurethane outer insulation but dependent on insulation integrity. The strongest extraction rail was seen with a simulated femoral snaring of a locking stylet within the INGEVITY lead. Deployed screw retraction was most successful by rotating a Philips LLD#2 stylet (Philips Healthcare, Amsterdam, Netherlands) within the lead. CONCLUSION Results from in vitro simulations of INGEVITY lead extraction from an atrial location found the lead has low maximum tensile strength resulting in a poor extraction rail with common extraction tools and methods. However, the strength of the INGEVITY Lead extraction rail can be significantly increased by leaving the lead terminal intact and femoral snaring of the locking stylet within the lead. Such techniques may improve extraction of the INGEVITY lead.

Lead extraction procedures have a low but real risk of major complications, such as superior vena cava tear and cardiac tamponade. Complications during lead removal are commonly related to lead binding sites, lead malposition, and lead perforation. Lead extraction imaging may indicate lead vascular binding sites, lead position, and perforation. Several imaging modalities are available, including chest radiograph, cardiac computed tomography, and echocardiography. The information provided by various imaging modalities will help assess the challenges of each lead extraction procedure and allows for better preprocedure planning.

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies.

Objectives This study investigated the applicability of the self-regulatory executive functioning (S-REF) model to performance test anxiety (PTA) in objective structured clinical examinations (OSCEs). Specifically, it examined the relative contributions of metacognitive beliefs, trait worry and attentional control to PTA. Methods A cross-sectional design was used. Immediately prior to their formative Communication for Clinical Practice OSCE, 240 Year 1 medical students completed the following self-report questionnaires: the Metacognitions Questionnaire-30 (MCQ-30); the Penn State Worry Questionnaire (PSWQ); the Attentional Control Scale (ACS), and the Performance Test Anxiety questionnaire (PTA). Results Univariate analysis indicated that female students scored significantly more highly than male students on the MCQ-30 subscale for negative beliefs about the uncontrollability and danger of worry, the MCQ-30 subscale for cognitive confidence and the PSWQ subscale for trait worry. Partial correlations (controlling for gender) showed that metacognitions, worry and attentional control were significantly correlated with PTA. Multiple regression analyses showed that worry and negative beliefs about the uncontrollability and danger of worry were independent predictors of PTA in both male and female students, whereas attention focus was an independent predictor only in male students. Conclusions The findings support predictions derived from the S-REF model that metacognitive beliefs, trait worry and attentional control processes underlie the onset and maintenance of PTA.

Background Electrical heterogeneity (EH) during cardiac resynchronization therapy may vary with different left ventricular (LV) pacing sites. Objective The purpose of this study was to evaluate the relationship between such changes and acute hemodynamic response (AHR). Methods Two EH metrics—standard deviation of activation times and mean left thorax activation times—were computed from isochronal maps based on 53-electrode body surface mapping during baseline AAI pacing and biventricular (BiV) pacing from different pacing sites in coronary veins in 40 cardiac resynchronization therapy–indicated patients. AHR at different sites was evaluated by invasive measurement of LV-dp/dt max at baseline and BiV pacing, along with right ventricular (RV)–LV sensing delays and QRS duration. Results The site with the greatest combined reduction in standard deviation of activation times and left thorax activation times from baseline to BiV pacing was hemodynamically optimal (defined by AHR equal to, or within 5% of, the largest dp/dt response) in 35 of 40 patients (88%). Sites with the longest RV–LV and narrowest paced QRS were hemodynamically optimal in 26 of 40 patients (65%) and 28 of 40 patients (70%), respectively. EH metrics from isochronal maps had much better accuracy (sensitivity 90%, specificity 80%) for identifying hemodynamically responsive sites (∆LV dp/dt max ≥10%) compared with RV–LV delay (69%, 85%) or paced QRS reduction (52%, 76%). Multivariate prediction model based on EH metrics showed significant correlation (R 2 = 0.53, P Conclusion Changes in EH from baseline to BiV pacing more accurately identified hemodynamically optimal sites than RV–LV delays or paced QRS shortening. Optimization of LV lead location by minimizing EH during BiV pacing, based on body surface mapping, may improve CRT response.

Treatment with a potent bisphosphonate is indicated in patients with Paget's disease who have symptoms likely to respond to reduced bone turnover at pagetic sites. In asymptomatic patients with active disease at sites susceptible to local progression and late complications, treatment is also recommended. Biochemical remission is achievable in a majority of patients with pamidronate, alendronate, risedronate, or zoledronic acid. Indications for medical treatment of active Paget's disease of bone include symptoms referable to sites of the disease such as bone pain, joint pain, and neurological complications; elective surgery at an active pagetic site to reduce intraoperative blood loss from highly vascular bone; management of rare instances of immobilization hypercalcemia with polyostotic disease; and presence of disease activity in asymptomatic patients at sites at risk for future complications to limit progression and possibly lower that risk. The treatment of choice is a potent nitrogen-containing bisphosphonate, including oral alendronate or risedronate or intravenous pamidronate or zoledronic acid. Etidronate and tiludronate are less potent and are second-line choices. Recent data with zoledronic acid indicate that a single infusion of 5 mg is associated with normalization of serum alkaline phosphatase in 89% of patients and a prolonged biochemical remission, making it the most effective therapy available to date. Side effect profiles with alendronate and risedronate include esophageal irritation in a minority of patients. Intravenous pamidronate and zoledronic acid may induce an acute phase reaction with fever and flu-like symptoms with the first dose, primarily in patients who are treatment naïve to nitrogen-containing bisphosphonates. Calcium and vitamin D repletion are mandatory with these potent anti-osteoclast therapies to avoid hypocalcemia. Acquired resistance to etidronate and pamidronate has been reported in some patients, leading to lesser reductions in bone turnover and shorter periods of remission, but substitution with a different bisphosphonate provides a more robust response. It is not known whether resistance to other bisphosphonates in Paget's disease occurs.

The purpose of the studies described here was to identify drug targets and develop a preclinical model for testing therapies that can reduce health disparities for Hispanic children with high-risk acute lymphoblastic leukemia (ALL). Hispanic children are 1.24 times more likely to develop ALL than non-Hispanic whites and that number rises to 2.09 by adolescence and early adulthood. A major contributor to this health disparity is a type high-risk B-cell ALL called CRLF2 B-ALL. CRLF2 B-ALL occurs 5 times more often in Hispanic children than others, is prevalent in adolescents and young adults, and is associated with a high relapse rate and poor prognosis. CRLF2 B-ALL is caused by genetic alterations that result in over expression of the cytokine receptor, CRLF2. The CRLF2 receptor is activated by the cytokine, TSLP, causing downstream activation of the JAK/STAT5 and PI3/AKT/MTOR pathways. A gene target of activated STAT5 in B cell precursors is Mcl-1, a Bcl2 family pro-survival molecule. In addition, Mcl-1 protein levels are known to be increased through post-transcriptional mechanisms by activation of the mTOR pathway. We hypothesized that the normal level of circulating TSLP cytokine could induce CRLF2 activation leading to increased Mcl-1 expression in CRLF2 B-ALL cells. Our data show that TSLP increases phosphorylation of STAT5, as well as AKT and S6 (downstream of mTOR) in primary CRLF2 B-ALL cells from Hispanic pediatric patients, even when activating JAK mutations are present. When CRLF2 B-ALL cells from Hispanic pediatric patients were cultured for 3 days with and without physiological levels of TSLP, flow cytometry showed that expression of the Mcl-1 protein was significantly increased in cultures with TSLP as compared to cultures without TSLP. CRLF2 B-ALL cells treated in vitro with Mcl-1 inhibitor showed dose-dependent increases in caspase 3 activation and apoptosis as indicated by flow cytometry. These data provide evidence that TSLP can contribute to leukemia cell survival and identify Mcl-1 inhibitor as a candidate therapy for CRLF2 B-ALL. Our next step was to develop a preclinical model for testing therapies that target genes, such as Mcl-1, that are regulated by TSLP-induced CRLF2 signals in this disease. Patient-derived xenograft (PDX) models produced by transplanting leukemia cells from patients into immune deficient mice provide an in vivo model of disease that includes contributions of the background genetic landscape that can influence disease progression or treatment outcome in health disparities diseases. PDX models are possible because most cytokines produced in the mouse are active on human cells, however mouse TSLP is species-specific. Thus classic PDX models do not provide TSLP that can activate the CRLF2 receptor that is overexpressed in CRLF2 B-ALL. To address this issue we engineered PDX mice to express physiological levels of human TSLP (+T PDX mice) and control -T mice that lacked human TSLP. In vivo TSLP activity was validated and +T PDX were successfully generated using leukemia cells from two Hispanic pediatric patients with CRLF2 B-ALL. To determine whether +T PDX mice provide a preclinical model of B-ALL that more closely mirrors patients than -T PDX mice, we compared RNAseq gene expression profiles of leukemia cells isolated from +T PDX and -T PDX mice to that from the original patient sample. The gene expression pattern in leukemia cells from +T mice was significantly closer to primary patient sample than that from -T mice. The +T PDX mice described here provide a novel in vivo preclinical model for evaluating efficacy of drugs, such as Mcl-1 inhibitor, in context of the background genetic landscape and physiological human TSLP present in patients. Citation Format: Kimberly J. Payne, Cornelia Stoian, Jacqueline S. Coats, Olivia Francis, Terry-Ann M. Milford, Ineavely Baez, Pierce J. McCarthy, George Mambo, Anna V.C. White, Mariah M.Z. Jackson, Juliette M. Personius, Veriah Vidales, Muhammad Omair Kamal, Shadi Farzin Gohar, Sinisa Dovat. A novel patient-derived xenograft model for evaluating therapies that target the CRLF2 signaling pathway to reduce health disparities for Hispanic children with leukemia. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr B46.

Though much research has been carried out on the effects of sexual abuse on the victim, and on the background and motivation of offenders, comparatively little has been conducted on the family members–the ‘secondary victims’ of abuse. It is these ‘forgotten victims’ who comprise the subjects of this qualitive study, looking at the effects of child sexual abuse on the child's non-abusing parent(s). The study focuses on sexual abuse by a family member or a trusted adult known to the child. Thirteen families of child sexual abuse victims took part in the study through a questionnarie and semi-structured interview. The participant's experiences highlight key counselling issues and, though links are made with the effects of loss and victimization, significant differences are also identified.

The cutaneous vascular anatomy of the mid-dorsum in the rat and its role in flap design was studied in the rat. The investigation consisted of anatomic dissection, methylene blue injection into the axial artery, and flap harvesting in live animals. Dissection and injection revealed that the mid-dorsum of the rat derives its blood supply largely from the 10th intercostal artery, here referred to as the middle dorsal artery, which originates from the lateral aspect of the thoracic aorta. The cutaneous vascular territory of the middle dorsal artery was defined as follows: the medial border, midline of the dorsum; the lateral border, midaxillary line; the cephalic border, a line joining the medial and lateral borders midway between the level of the axilla proximally and 1 cm above the base of the rib cage distally; and the caudal border, a line drawn midway between the latter point proximally and the anterior superior iliac spine distally. Both unilateral and bilateral vascular pedicled island cutaneous flaps were harvested in living rats based on and exceeding the vascular territory delimited by methylene blue injection. Flaps limited to this territory with intact middle dorsal arteries showed total survival, while oversized flaps underwent partial necrosis peripherally. Because of its simplicity, reliability, and consistent vascularity, this flap has potential applications in the study of flap hemodynamics.

We describe 3 cases of Ochrobactrum anthropi meningitis following the implantation of pericardial allograft tissue to cover dural defects following craniotomy. Following an extensive epidemiologic investigation, the tissue allograft was found to have been contaminated with this unusual organism during the harvesting and processing of the tissue in the tissue bank. This organism was only susceptible to imipenem, tetracycline, gentamicin, and ciprofloxacin. The clinical presentation of these patients was subacute. Two of the patients developed osteomyelitis of the bone flap; while another developed a relapse of infection along a former ventriculoperitoneal shunt track 6 months after the initial infection. Appropriate clinical outcome was only observed after removal of tissue allograft implants, debridement of devitalized tissue and bone, removal of shunt devices, and prolonged courses of antibiotics. No deaths were observed.

Proximal tibial osteotomy in the growing patient historically has been associated with a high rate of neurovascular complications and malunion. Here is reported a technique of valgus proximal tibial osteotomy, of the incomplete closing wedge type, that has avoided neurovascular compromise while achieving reliable correction and rapid bony union. Oblique proximal tibial valgus osteotomies with lateral tension plate fixation were performed on 18 tibiae in 14 patients (age range, 5-25 years) with tibia vara. The primary diagnosis was Blount's disease in 13 tibiae, achondroplasia in 2 tibiae, multiple epiphyseal dysplasia in 2 tibiae, and hypochondroplasia in 1 tibia. No postoperative plaster immobilization was necessary. All patients were able to bear weight fully by 8 weeks after surgery. Average angular correction was 18 degrees. One patient had overcorrection because of an unrecognized intraoperative fracture of the media] tibial cortex. There were no neurovascular complications. No growth disturbance of the proximal tibial physis was noted. Oblique proximal tibial osteotomy with tension plate fixation successfully corrected varus deformity of the proximal tibia in the growing patient without damage to the proximal tibial physis or neurovascular compromise.

The most common arrhythmias associated with inferior-wall and anterior-wall myocardial infarction are bradycardia and supraventricular and ventricular tachycardia. Optimal treatment approaches are based on the pathophysiology of the infarct and the presence of contributing medical factors (eg, congestive heart failure, metabolic disorders). Temporary or permanent pacemaker therapy is helpful in some patients. Sudden death due to arrhythmia after myocardial infarction may be predicted and avoided in certain situations.

This study evaluated the recovery after exercise of both ST-segment depression on the exercise electrocardiogram (electrical evidence of ischemia) and exercise-induced abnormalities in wall motion or ejection fraction as detected by radionuclide angiography. The study group of 31 patients was selected to undergo prolonged electrocardiographic and radionuclide imaging after exercise because they had persistent ST-segment depression greater than 3 minutes after exercise and radionuclide angiographic evidence of ischemia at peak exercise. In 27 (87%) of the 31 patients, radionuclide evidence of ischemia recovered more quickly than the electrocardiogram. Only 15 of the 31 patients had exercise-induced radionuclide abnormalities after exercise. Compared with the 16 patients without such findings of ischemia after exercise, these 15 patients had a worse wall motion score at peak exercise (5.3 vs 3.9; p less than 0.01) and a smaller increase in systolic blood pressure with exercise (p less than 0.05) and after exercise (p less than 0.01). Radionuclide angiographic evidence of ischemia recovers more quickly after exercise than ST-segment depression. When there is radionuclide evidence of ischemia after exercise, it is associated with more severe ischemia during exercise.

To improve the predictive accuracy of the signal-averaged electrocardiogram, we created a linear logistic model for predicting ventricular tachycardia during electrophysiologic testing. This signal-averaged electrocardiographic model was created from data obtained from 214 patients undergoing electrophysiologic testing (70 had ventricular tachycardia during electrophysiologic testing) by using stepwise logistic regression to rank eight clinical and nine signal-averaged electrocardiographic variables. The best predictors were ejection fraction, history of infarction, ventricular ectopic pairs or nonsustained ventricular tachycardia on Holter monitoring, QRS duration after 25-Hz filtering, and root mean square voltage of the terminal 40 msec of the QRS complex after 40- and 80-Hz filtering. Cross validation (a statistical technique that can be used to accurately evaluate how a predictive model will perform on a prospective patient population) was used to validate the model. After cross validation, the model's sensitivity was 91% and specificity was 59% for predicting ventricular tachycardia during electrophysiologic testing. This model compared favorably with established 25-Hz late-potential criteria (QRS duration of more than 110 msec and root mean square voltage of less than 25 microV of the terminal 40 msec of the QRS complex; sensitivity, 64%; specificity, 85%) and with established 40-Hz late-potential criteria (QRS duration of more than 114 msec or root mean square voltage of less than 20 microV of the terminal 40 msec of the QRS complex or duration of the low-amplitude signal less than 40 microV at the terminal QRS complex that is greater than 38 msec; sensitivity, 84%; specificity, 54%).(ABSTRACT TRUNCATED AT 250 WORDS)

Summary The signal-averaged ECG has proven to be a valuable tool for identifying patients at risk of ventricular arrhythmias. This computerized method of analyzing standard ECGs identifies microvolt-level late potentials that represent delayed conduction through diseased myocardium. This diseased myocardium is a potential substrate for reentrant ventricular arrhythmias. In select patient groups, the signal-averaged ECG predicts electrophysiologic testing results. Problems remain and continued development is needed to evaluate patients with conduction system disease, the patient without coronary artery disease but at risk of sudden death, and proper general application of the technique.

The use of thrombolytic agents is an important contributor to the improved prognosis following acute myocardial infarction observed over the last 20 years1-5. Thrombolytic agents result in modestly improved ventricular function1,5,6 although these changes are minimal and do not account for the beneficial effects of reperfusion on subsequent mortality following myocardial infarction. A mechanism by which restoration of patency of the infarct-related artery could improve survival is alteration of the electrophysiological substrate for the development of life-threatening ventricular arrhythmias. Several recent studies7–12 have evaluated the relationship between patency of the infarct-related artery, the presence of late potentials detected by signal averaged ECG and subsequent mortality in patients with acute myocardial infarction.

This study evaluated the relation between patency of the infarct-related artery and the presence of late potentials on the signal-averaged electrocardiogram (ECG) in 124 consecutive patients (98 men, 26 women; mean age 59 years) with acute myocardial infarction receiving thrombolytic therapy, acute percutaneous transluminal coronary angioplasty or standard care. All patients were studied by coronary angiography, measurement of ejection fraction and signal-averaged ECG. The infarct-related artery was closed in 51 patients and open in 73. Among patients with no prior myocardial infarction undergoing early attempted reperfusion therapy, a patent artery was associated with a decreased incidence of late potentials (20% versus 71%; no significant difference in ejection fraction). In the 48 patients receiving thrombolytic agents within 4 h of symptom onset, the incidence of late potentials was 24% and 83% among patients with an open or closed artery, respectively (p less than 0.04). The most powerful predictors of late potentials were the presence of a closed infarct-related artery, followed by prior infarction and patient age. Among patients receiving thrombolytic agents within 4 h of symptom onset, the only variable that was predictive of the presence of late potentials was a closed infarct-related artery. These data imply that reperfusion of an infarct-related artery has a beneficial effect on the electrophysiologic substrate for serious ventricular arrhythmias that is independent of change in left ventricular ejection fraction as an index of infarct size. These findings might explain, in part, the low late mortality rate in survivors of myocardial infarction with documented reperfusion of the infarct-related artery.

One hundred ten patients with asymptomatic nonsustained ventricular tachycardia (VT) were evaluated prospectively to assess the value of electrophysiologic testing. This testing consisted of up to 3 extrastimuli delivered during 3 drive cycle lengths from 2 right ventricular sites. A positive study was defined as monomorphic VT lasting 30 seconds or requiring cardioversion. Patients with a positive study were treated, and serial drug testing was done. An event during follow-up was sustained VT or cardiac arrest. The mean follow-up was 15 months. Of 57 patients with an ejection fraction greater than or equal to 40%, 6 had a positive electrophysiologic test with 1 event and 51 had a negative test with 1 event. Twenty-eight patients had an ejection fraction less than 40% and coronary artery disease: 14 had a positive test with 1 event, and 14 had a negative test with 3 events. Twenty-five patients had an ejection fraction less than 40% and no coronary artery disease: 1 had a positive test with no events, and 24 had a negative test with 8 events. Only ejection fraction and congestive heart failure class were found to be independent predictors of outcome. Patients with an ejection fraction greater than 40% had low inducibility (11%), had few events (3.5%) and did not require electrophysiologic testing. In patients with an ejection fraction less than 40% and coronary artery disease, inducibility was high (50%) and a negative study was of no value. Patients with an ejection fraction less than 40% and no coronary artery disease had low inducibility (4%), had frequent events (33%) and did not benefit from electrophysiologic testing.

We describe 3 patients who presented with severe cardiac disability as a result of tricuspid insufficiency, in the setting of severe coronary disease. Pertinent physical findings were signs of right heart failure, a tricuspid regurgitant murmur, and absence of left heart failure. Echocardiography and subsequent cardiac catheterization demonstrated significant tricuspid insufficiency, dilated right ventricle, impairment of right ventricular function, and preserved left ventricular function. Two patients were treated successfully with DeVega annuloplasty. Symptomatic tricuspid insufficiency can be seen in the setting of coronary artery disease and, when left ventricular function is well preserved, surgical correction is feasible.

Signal-averaged electrocardiography (ECG) is a new noninvasive test for identifying patients at risk for ventricular arrhythmias. This computerized method of analyzing standard ECGs identifies particular microvolt-level signals called late potentials. Late potentials have been correlated with clinical ventricular tachycardia, are predictive of ventricular tachycardia inducibility at the time of electrophysiologic testing, and are predictive of arrhythmic events after myocardial infarction. In this review, we describe late potentials, the method of obtaining and processing the signal-averaged ECG, and clinical studies in various patient groups that have assessed the predictive value of the signal-averaged ECG for identification of patients at risk for subsequent ventricular arrhythmias.

Between 1961 and 1984, 91 patients underwent simultaneous triple valve replacement at the Mayo Clinic. Of the 273 prosthetic valves used, 77% were Starr-Edwards. Perioperative (30 day) mortality was 24% to 27% between 1962 and 1974 and 7% between 1975 and 1983 (p = .17). In patients with NYHA class IV symptoms, perioperative mortality was 44%, and in those with milder symptoms, it was 8% (p less than .0001). The median follow-up was 7.5 years (range, 6 weeks to 20 years). Cumulative survival, which was calculated taking into consideration perioperative mortality, was 64% at 1 year, 55% at 5 years, 40% at 10 years, and 25% at 15 years. Multivariate analysis identified preoperative functional class and age as predictors of late survival. Among causes of late mortality were sudden death in 32.5%, congestive heart failure in 15%, thromboembolism in 12.5%, prosthetic valve dysfunction in 7.5%, and infective endocarditis in 5%. Late complications included systemic emboli in 42% (embolic rate, 12.3 events per 100 patient-years), bleeding in 22%, myocardial infarction in 16%, and infective endocarditis in 6%. Eight patients required reoperation for prosthetic valve dysfunction, and 12 patients had permanent pacemakers. Of the 29 patients still alive, 79% are in NYHA class I or II. In summary, perioperative mortality after triple valve replacement appears to be declining; long-term survival in 30 day survivors is similar to that after single valve replacement and excellent symptomatic improvement can be obtained, although morbidity is high.

A case of Cushing's syndrome in a 15-year-old girl with symptoms of one year's duration, is described. The levels of plasma and urinary 17-hydroxycorticostcroids and urinary 17-ketogenic steroids were elevated but the levels of urinary 17-ketosteroids and pregnanetriol were normal. Stimulation with ACTH produced a low, sluggish response in the concentration of plasma 17-hydroxycorticosteroids and only minimal changes in urinary steroids. Administration of 9α-fluorohydrocortisone produced no change in urinary steroid excretion. Following bilateral adrenalectomy the manifestations of Cushing's syndrome disappeared. The adrenals showed diffuse multinodularity of the inner cortex. The relation of this lesion to other adrenal lesions producing Cushing's syndrome is discussed. MELLINGER and Smith in 1956 reported an unusual case of Cushing's syndrome of about thirty years' duration in a patient who had multiple small nodules throughout the cortex of one adrenal. Biopsy of the same gland earlier in the ...

DDD pacemakers offer a physiologic form of pacing for selected patients by incorporating atrioventricular synchrony over a wide range of atrial rates. Selection of a patient for DDD pacing necessitates a thorough knowledge of the individual functions of the DDD pacemaker, the limitations of DDD pacing, and the patient's own electrical and physiologic needs. Continuing developments in cardiac pacing include further reduction of the possibility of pacemaker-mediated tachycardia, increased matching to metabolic needs, and advancement of telemetric technology and electrophysiologic testing.

Ce syndrome associe chez la malade une premiere tumeur dans sa jeunesse, un myxome recidivant une localisation atypique de cette tumeur a la base de la veine cave inferieure, des ephelides et des tumeurs multiples de la peau

Giant cell tumor of bones are usually located in the long tubular bones and rarely located in the proximal end of the radius. This is a case report of a giant cell tumor in the proximal radius in a 35-year-old woman treated successfully with curettage and bank bone graft.

One of the more uncommon causes of acute intestinal obstruction is impaction of a gallstone in the intestinal lumen. Almost without exception, this is the result of a spontaneous internal biliary fistula, occurring most frequently between the gallbladder and the duodenum. A gallstone ileus, in the absence of a previous communication between intestine and biliary tree, is, however, a rare occurrence; only two such cases have been discovered in the literature. The site of formation of the stone in one of these cases was a duodenal diverticulum 1 and in the other a blind duodenal stump following subtotal gastrectomy. 2 It is the purpose of this report to review briefly the problem of gallstone obstruction of the intestinal tract and to present a third case of acute intestinal obstruction resulting from impaction of a large gallstone in the terminal ileum in the absence of a previous biliary-tract fistula. Incidence In

Unilateral spatial neglect is a neuropsychological syndrome commonly observed after stroke and defined by the inability to attend or respond to contralesional stimuli. Typically, symptoms are assessed using clinical tests that rely upon visual/perceptual abilities. However, neglect may affect high-level representations controlling attention in other modalities as well. Here we developed a novel manual exploration test using a touch screen computer to quantify spatial search behaviour without visual input. Twelve chronic stroke patients with left neglect and 27 patients without neglect (based on clinical tests) completed our task. Four of the 12 "neglect" patients exhibited clear signs of neglect on our task as compared to "non-neglect" patients and healthy controls, and six other patients (from both groups) also demonstrated signs of neglect compared to healthy controls only. While some patients made asymmetrical responses on only one task, generally, patients with the strongest neglect performed poorly on multiple tasks. This suggests that representations associated with different modalities may be affected separately, but that severe forms of neglect are more likely related to damage in a common underlying representation. Our manual exploration task is easy to administer and can be added to standard neglect screenings to better measure symptom severity.

Immune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, the polymorphic nature of the locus has precluded accurate HLA copy-number analysis. Here, we present loss of heterozygosity in human leukocyte antigen (LOHHLA), a computational tool to determine HLA allele-specific copy number from sequencing data. Using LOHHLA, we find that HLA LOH occurs in 40% of non-small-cell lung cancers (NSCLCs) and is associated with a high subclonal neoantigen burden, APOBEC-mediated mutagenesis, upregulation of cytolytic activity, and PD-L1 positivity. The focal nature of HLA LOH alterations, their subclonal frequencies, enrichment in metastatic sites, and occurrence as parallel events suggests that HLA LOH is an immune escape mechanism that is subject to strong microenvironmental selection pressures later in tumor evolution. Characterizing HLA LOH with LOHHLA refines neoantigen prediction and may have implications for our understanding of resistance mechanisms and immunotherapeutic approaches targeting neoantigens. VIDEO ABSTRACT.

A total of 44 preterm fetal lambs at great risk of developing respiratory failure were delivered by Cesarean section, and were then managed on conventional mechanical pulmonary ventilation. Fifteen animals initially fared well, and 14 of these were long term survivors. Twenty-nine other lambs showed a progressive deterioration in arterial blood gases within 30 minutes of delivery, of which 10 lambs were continued on mechanical pulmonary ventilation (20% survival), while the remaining 19 lambs were placed on an extracorporeal membrane lung respiratory assist (79% survival). Extracorporeal membrane lung bypass rapidly corrected arterial blood gas values, and permitted the use of high levels of CPAP instead of the continuation of mechanical pulmonary ventilation at high peak airway pressures. Improvement in lung function was gradual, and predictable. Early institution of extracorporeal respiratory assist using a membrane artificial lung rapidly corrected arterial blood gas values and significantly improved on neonate survival.