Strong Memorial Hospital

Cells with properties characteristic of mononuclear phagocytes were evaluated for infectivity with five different isolates of the AIDS virus, HTLV-III/LAV. Mononuclear phagocytes cultured from brain and lung tissues of AIDS patients harbored the virus. In vitro-infected macrophages from the peripheral blood, bone marrow, or cord blood of healthy donors produced large quantities of virus. Virus production persisted for at least 40 days and was not dependent on host cell proliferation. Giant multinucleated cells were frequently observed in the macrophage cultures and numerous virus particles, often located within vacuole-like structures, were present in infected cells. The different virus isolates were compared for their ability to infect macrophages and T cells. Isolates from lung- and brain-derived macrophages had a significantly higher ability to infect macrophages than T cells. In contrast, the prototype HTLV-III beta showed a 10,000-fold lower ability to infect macrophages than T cells and virus production was one-tenth that in macrophage cultures infected with other isolates, indicating that a particular variant of HTLV-III/LAV may have a preferential tropism for macrophages or T cells. These results suggest that mononuclear phagocytes may serve as primary targets for infection and agents for virus dissemination and that these virus-infected cells may play a role in the pathogenesis of the disease.

BACKGROUND: In 1994, an International Task Force proposed criteria for the clinical diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) that facilitated recognition and interpretation of the frequently nonspecific clinical features of ARVC/D. This enabled confirmatory clinical diagnosis in index cases through exclusion of phenocopies and provided a standard on which clinical research and genetic studies could be based. Structural, histological, electrocardiographic, arrhythmic, and familial features of the disease were incorporated into the criteria, subdivided into major and minor categories according to the specificity of their association with ARVC/D. At that time, clinical experience with ARVC/D was dominated by symptomatic index cases and sudden cardiac death victims-the overt or severe end of the disease spectrum. Consequently, the 1994 criteria were highly specific but lacked sensitivity for early and familial disease. METHODS AND RESULTS: Revision of the diagnostic criteria provides guidance on the role of emerging diagnostic modalities and advances in the genetics of ARVC/D. The criteria have been modified to incorporate new knowledge and technology to improve diagnostic sensitivity, but with the important requisite of maintaining diagnostic specificity. The approach of classifying structural, histological, electrocardiographic, arrhythmic, and genetic features of the disease as major and minor criteria has been maintained. In this modification of the Task Force criteria, quantitative criteria are proposed and abnormalities are defined on the basis of comparison with normal subject data. CONCLUSIONS: The present modifications of the Task Force Criteria represent a working framework to improve the diagnosis and management of this condition. Clinical Trial Registration clinicaltrials.gov Identifier: NCT00024505.

BACKGROUND: Infants with cardiac disease or prematurity are at risk for severe illness caused by respiratory syncytial virus. Immune globulin with a high titer of antibodies against respiratory syncytial virus may offer infants and young children at risk protection from this serious, common respiratory illness. METHODS: We studied 249 infants and young children (mean age, eight months) who had bronchopulmonary dysplasia due to prematurity (n = 102), congenital heart disease (n = 87), or prematurity alone (n = 60). Respiratory syncytial virus immune globulin was given monthly to some of these children in either a high dose (750 mg per kilogram of body weight; n = 81) or low dose (150 mg per kilogram; n = 79); 89 controls received no immune globulin. Group assignments were random. Assessments of respiratory illness and management were conducted without knowledge of the children's group assignments. RESULTS: There were 64 episodes of respiratory syncytial virus infection: 19 in the high-dose group, 16 in the low-dose group, and 29 in the control group. In the high-dose group there were fewer lower respiratory tract infections (7, vs. 20 in the control group; P = 0.01), fewer hospitalizations (6, vs. 18 in the control group; P = 0.02), fewer hospital days (43, vs. 128 in the control group; P = 0.02), fewer days in the intensive care unit (P = 0.05), and less use of ribavirin (P = 0.05). In the low-dose group there was a significant reduction only in the number of days in the intensive care unit (P = 0.03). Adverse events during the 580 infusions were generally mild and included fluid overload (in five children), oxygen desaturation (eight), and fever (six). Six children died: three in the high-dose group, three in the low-dose group, and none in the control group (P = 0.15), but no death was attributed to the use of immune globulin or to illness caused by respiratory syncytial virus. CONCLUSIONS: Administration of high doses of respiratory syncytial virus immune globulin is a safe and effective means of preventing lower respiratory tract infection in infants and young children at high risk for this disease.

We performed a randomized, double-blind, controlled six-month trial of prednisone in 103 boys with Duchenne's muscular dystrophy (age, 5 to 15 years). The patients were assigned to one of three regimens: prednisone, 0.75 mg per kilogram of body weight per day (n = 33); prednisone, 1.5 mg per kilogram per day (n = 34); or placebo (n = 36). The groups were initially comparable in all measures of muscle function. Both prednisone groups had significant improvement of similar degree in the summary scores of muscle strength and function. Improvement began as early as one month and peaked by three months. At six months the high-dose prednisone group, as compared with the placebo group, had improvement in the time needed to rise from a supine to a standing position (3.4 vs. 6.2 seconds), to walk 9 m (7.0 vs. 9.7 seconds), and to climb four stairs (4.0 vs. 7.1 seconds), in lifting a weight (2.1 vs. 1.2 kg), and in forced vital capacity (1.7 vs. 1.5 liters) (P less than 0.001 for all comparisons). There was an increase in urinary creatinine excretion (261 vs. 190 mg per 24 hours), which suggested an increase in total muscle mass. However, the prednisone-treated patients who had required long-leg braces (n = 5) or wheelchairs (n = 11) continued to require them. The most frequent side effects were weight gain, cushingoid appearance, and excessive hair growth. We conclude from this six-month study that prednisone improves the strength and function of patients with Duchenne's muscular dystrophy. However, further research is required to identify the mechanisms responsible for these improvements and to determine whether prolonged treatment with corticosteroids may be warranted despite their side effects.

OBJECTIVE: To assess efficacy and safety of once-daily 8 or 12 mg perampanel, a noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor antagonist, when added to concomitant antiepileptic drugs (AEDs) in the treatment of drug-resistant partial-onset seizures. METHODS: This was a multicenter, double-blind, placebo-controlled trial (ClinicalTrials.gov identifier: NCT00699972). Patients (≥12 years, with ongoing seizures despite 1-3 AEDs) were randomized (1:1:1) to once-daily perampanel 8 mg, 12 mg, or placebo. Following baseline (6 weeks), patients entered a 19-week double-blind phase: 6-week titration (2 mg/week increments to target dose) followed by a 13-week maintenance period. Percent change in seizure frequency was the primary endpoint; 50% responder rate was the primary endpoint for EU registration. RESULTS: Of 388 patients randomized and treated, 387 provided seizure frequency data. Using this intent-to-treat population over the double-blind phase, the median percent change in seizure frequency was -21.0%, -26.3%, and -34.5% for placebo and perampanel 8 and 12 mg, respectively (p = 0.0261 and p = 0.0158 for 8 and 12 mg vs placebo, respectively). Fifty percent responder rates during the maintenance period were 26.4%, 37.6%, and 36.1%, respectively, for placebo, perampanel 8 mg, and perampanel 12 mg; these differences were not statistically significant for 8 mg (p = 0.0760) or 12 mg (p = 0.0914). Sixty-eight (17.5%) patients discontinued, including 40 (10.3%) for adverse events. Most frequent treatment-emergent adverse events were dizziness, somnolence, irritability, headache, fall, and ataxia. CONCLUSIONS: This trial demonstrated that once-daily, adjunctive perampanel at doses of 8 or 12 mg improved seizure control in patients with uncontrolled partial-onset seizures. Doses of perampanel 8 and 12 mg were safe, and tolerability was acceptable. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that once-daily 8 and 12 mg doses of adjunctive perampanel are effective in patients with uncontrolled partial-onset seizures.

Ultrasound cardiography has become established as a valuable clinical tool in the detection of pericardial effusion (1) and the study of mitral valve disease (2, 3). The tricuspid valve can also be detected (4), and studies have been made of left ventricular stroke volume (5) and wall thickness (6). On the other hand, the extension of the ultrasonic method to the study of other cardiac structures has been slow because of the difficulty in recognizing the source of the echoes. Even here, however, Edler (7) has gained useful knowledge in the recognition of the origin of these echoes by the passing of needles into cadavers in duplication of the path of the ultrasonic beam and by the study of excised hearts. The purpose of this presentation is to describe a method for the ultrasonic identification of the cardiac chambers in the living subject. It is based on the intracardiac injection of substances that produce echoes at the site of injection as well as downstream in the flow pattern and permit identification of the heart cavities. The identification of the cardiac chambers without contrast injection is a natural outcome of this study and depends on the distinguishing of key anatomic structures, the relationship of the chambers to them, and the recognition of movement patterns that may be specific for a structure or chamber. Background Ultrasound was developed during the period following World War I for depth-sounding and localization of submarines and schools of fish. The emergence of technics for the measurement of very short periods of time permitted Firestone, in 1945, to use ultrasound in the nondestructive testing of materials (8). These same principles were employed by Edler and Hertz in 1954 to study heart motion and to initiate echocardiography as a clinical tool (9). Their method is in general use today. To summarize, short bursts (one to two microseconds) of ultrasonic energy are emitted by a transducer held in close contact with the skin. As this sound energy passes through tissue, it is reflected at interfaces of differing acoustic impedance to the same transducer, which also acts as a receiver between pulses. The time that elapses between the generation of the pulse of ultrasound and the arrival of the echo is a measure of the depth of the reflecting surface. The high frequency of the pulses (200 to 2,000 per second) offers many determinations per cardiac cycle and permits accurate and detailed tracking of rapidly moving structures, such as heart-valve cusps the velocities of which are often in excess of 250 mm per second (2). The echo pattern is usually displayed on the face of an oscilloscope by either of two methods. "A" mode shows the returning signals as spikes that oscillate back and forth on the x-axis as the depth of the reflecting surface changes. The size of the peak is proportional to the intensity of the recording signal. "A" mode is useful primarily for identification and location of echoes.

Among the 62 responders, median duration of response was not estimable (NE; 95% confidence interval [CI], 13.6-NE). At a median follow-up of 13.1 months, the median progression-free survival was 8.8 (95% CI, 4.6-15.4) months and median overall survival was 17.5 (95% CI, 13.3-NE) months. The estimated 12-month survival rate was 66% (95% CI, 55.6-74.8). Aside from increased neutropenia, the safety profile of daratumumab plus pom-dex was consistent with that of the individual therapies. Deep, durable responses were observed in heavily treated patients. The study was registered at www.clinicaltrials.gov as #NCT01998971.

Simultaneous recordings of reflected ultrasound from the anterior mitral leaflet and left ventricular outflow, the ECG, the phonocardiogram, and a recording of the carotid artery pulse were obtained in six patients with hypertrophic obstructive cardiomyopathy. Abnormal sharp systolic anterior movement (SAM) of the mitral leaflet was observed. This movement began with the onset of ventricular ejection and reached a peak with the initial peak in the arterial pulse. The leaflet was apposed to the interventricular septum up to 60% of the ejection period. In the latter part of systole as the mitral leaflet moved away from the interventricular septum, the arterial pulse showed a second systolic wave. Onset of SAM coincided with onset of the systolic murmur. Spontaneous variations in amplitude of SAM coincided with alterations in contour of the arterial pulse and in the intensity of the murmur. Administration of methoxamine to four patients resulted in disappearance of SAM. In one patient following surgery, the SAM of the mitral leaflet was noted only in the post-ectopic beats. This specific abnormality of mitral leaflet movement represents the localization of dynamic outflow obstruction in hypertrophic obstructive cardiomyopathy.

CONTEXT: Immunization rates for children and adults remain below national goals. While experts recommend that health care professionals remind patients of needed immunizations, few practitioners actually use reminders. Little is known about the effectiveness of reminders in different settings or patient populations. OBJECTIVES: To assess the effectiveness of patient reminder systems in improving immunization rates, and to compare the effectiveness of different types of reminders for a variety of patient populations. DATA SOURCES: A search was performed using MEDLINE, EMBASE, PsychINFO, Sociological Abstracts, and CAB Health Abstracts. Relevant articles, as well as published abstracts, conference proceedings, and files of study collaborators, were searched for relevant references. STUDY SELECTION AND DATA EXTRACTION: English-language studies involving patient reminder/recall interventions (using criteria established by the Cochrane Collaboration) were eligible for review if they involved randomized controlled trials, controlled before-after studies, or interrupted time series, and measured immunization rates. Of 109 studies identified, 41 met eligibility criteria. Studies were reviewed independently by 2 reviewers using a standardized checklist. Results of studies are expressed as absolute percentage-point changes in immunization rates and as odds ratios (ORs). Studies with similar characteristics of patients or interventions were pooled (random effects model). DATA SYNTHESIS: Patient reminder systems were effective in improving immunization rates in 33 (80%) of the 41 studies, irrespective of baseline immunization rates, patient age, setting, or vaccination type. Increases in immunization rates due to reminders ranged from 5 to 20 percentage points. Reminders were effective for childhood vaccinations (OR, 2.02; 95% confidence interval [CI], 1.49-2.72), childhood influenza vaccinations (OR, 4. 25; 95% CI, 2.10-8.60), adult pneumococcus or tetanus vaccinations (OR, 5.14; 95% CI, 1.21-21.78), and adult influenza vaccinations (OR, 2.29; 95% CI, 1.69-3.10). While reminders were most effective in academic settings (OR, 3.33; 95% CI, 1.98-5.58), they were also highly effective in private practice settings (OR, 1.79; 95% CI, 1. 45-2.22) and public health clinics (OR, 2.09; 95% CI, 1.42-3.07). All types of reminders were effective (postcards, letters, and telephone or autodialer calls), with telephone reminders being most effective but costliest. CONCLUSIONS: Patient reminder systems in primary care settings are effective in improving immunization rates. Primary care physicians should use patient reminders to improve immunization delivery. JAMA. 2000;284:1820-1827.

7019 Background: The value of adjuvant chemotherapy in resectable lung cancer remains controversial. The International Adjuvant Lung Trial (IALT) reported a modest but statistically significant survival advantage with cisplatin-based adjuvant chemotherapy in stages IA to III NSCLC. On the other hand, Adjuvant Lung Project Italy (ALPI) failed to demonstrate benefit for adjuvant chemotherapy in patients of similar stage. CALGB 9633 was designed to test the effectiveness of adjuvant chemotherapy in patients with T2N0M0, stage IB NSCLC. NCCTG and RTOG also participated. Methods: Within 4–8 weeks of resection, patients were randomized to adjuvant chemotherapy with paclitaxel 200 mg/m2 over 3 hours and carboplatin AUC 6, each administered on day one every three weeks for four cycles, or to observation. Eligibility: age >18 years, histologically documented NSCLC, T2 primary lesion, lobectomy or pneumonectomy, absence of tumor in N1 or N2 nodes sampled at surgery or mediastinoscopy. All p-values are two-sided. Results: Between 9/15/96 and 11/26/03, 344 patients were randomized. Median follow-up is currently 34 months. Median age was 61 years (range 34–81 years), and 64% were male. Groups were well balanced with regard to age, gender, race, ethnicity, histology, tumor differentiation, and resection type. 80% underwent mediastinoscopy prior to surgery. Lobectomy was performed in 89%. Adjuvant chemotherapy was well tolerated, and there were no chemotherapy-related toxic deaths. Grade III or IV neutropenia occurred in 36%. There have been 36 deaths from any cause among 173 patients in the chemotherapy group compared to 52 deaths among 171 patients in the observation group (HR=0.62; 95% CI: 0.41–0.95, p=0.028). Overall survival at 4 years is 71% (95% CI: 62%–81%) and 59% (95% CI: 50%–69%) in chemotherapy and observation groups, respectively. There was also a significant advantage in failure-free survival favoring the chemotherapy group (HR=0.69; 95% CI: 0.48–0.98; p=0.035). With regard to lung cancer mortality, there have been 19 lung cancer deaths in the chemotherapy group and 34 deaths in the control group (HR=0.51; 95% CI: 0.29–0.89; p=0.018). At 4 years, lung cancer mortality was 15% (95% CI: 8%–21%) and 26% (95% CI: 18%–34%) in chemotherapy and control groups, respectively. Conclusions: Adjuvant chemotherapy significantly reduces all-cause and lung cancer mortality in stage IB NSCLC. This is the first randomized trial to demonstrate significantly improved survival for a carboplatin-based adjuvant chemotherapy regimen in a uniform population with NSCLC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Aventis

A prospective study of 114 patients with DMD provided data for "power" calculations for future therapeutic trials. There was a decline in strength of 0.4 units per year (on a 0-10 scale). Contractures of the iliotibial bands, hip flexors, and heel cords developed before 6 years. Contractures of other joints accompanied the increased use of wheelchairs. All children walked until 8 years with functional "improvement" between 3-6 years. Children of the same age varied widely in their strength, degree of contracture, and functional abilities. Fifteen percent of the patients appear to have a milder variety of the disease and are termed "outliers." To test a drug which might slow the disease to 25% of its original rate of progression, two groups (placebo and treatment) of 40 patients each would have to be followed for one year.

A study of how well children took oral penicillin when prescribed for streptococcal pharyngitis or otitis media was conducted in three private pediatric group practices. The presence of penicillin in the urine, as determined by the Sarcina lutea culture method, was used to assess the compliance rate. A total of 459 patients were studied—107 at five days of therapy and 352 at nine days. Eighty-one percent of the patients were taking the penicillin as prescribed on the fifth day, and 56% were taking it on the ninth day. Another 13% were erratic takers at the end of therapy. The children with pharyngitis were somewhat more likely to complete therapy than those with otitis media. A number of factors were studied in an attempt to differentiate those who complied with the therapy from those who did not. The take rate was unrelated to age or sex of the child, duration of symptoms, or doctor's estimate of severity of disease at onset. It was correlated with mother's estimate of severity, whether or not their usual doctor prescribed the medicine, and certain personality traits of the mother as perceived by the pediatrician. The implications of the study for the use of oral therapy in children are discussed.

Irradiation of enlarged thymus glands in infancy, a practice started by Friedlander in 1907 (1), was commonplace in this country from 1930 to 1945. Since many parents and physicians still firmly believe that thymic enlargement is a potentially dangerous condition, x-ray treatments continue to be given to young children with this diagnosis. Because of our interest in possible late sequelae of such x-ray therapy, we have undertaken a survey to determine the present health of 1,722 children treated between 1926 and 1951. Data on the 1,400 children traced to date show that the incidence of malignant neoplasia is high, acute leukemia and thyroid carcinoma being the most common forms of the disease. The high cancer rate in the treated groups is significantly above that in 1,795 untreated siblings and in the general population of the same age distribution. Although the medical literature contains numerous warnings about the possible dangers of the widespread and indiscriminate use of x-rays in the treatment of enlargement of the thymus gland, no concrete substantiating evidence has been presented. Duffy and Fitzgerald (2) suggested a possible association between thyroid cancer in childhood or adolescence and prior irradiation to the thymus gland. In 10 of their series of 28 cases of carcinoma of the thyroid there was a history of x-ray treatment. Two subsequent papers reviewing other series of childhood cancers of the thyroid do not report a history of irradiation (3, 4). Recently Dameshek (5) commented that in one month he had seen 3 children with leukemia who had received roentgen therapy to enlarged thymus glands. Previous attempts to follow children who had received x-ray therapy for thymic enlargement are limited in number and scope. In 1936, Polk and Rose (6) reported a study on 31 of 55 children treated before 1924. Only 18 of the children were less than eighteen months old when treated. One child died of leukemia, but this was only two weeks after treatment. In 1938, Kerley (7) noted that 27 patients were mentally and physically normal twenty-six weeks to sixteen years after irradiation. Conti and Patton (8) reported on a series of 7,400 consecutive newborn infants seen between 1937 and 1946. In the early part of their study, the 3 to 4 per cent of infants found to have roentgen evidence of thymic enlargement were given x-ray therapy whether or not they had symptoms. Later all infants received small doses of x-rays. As this appeared to increase the incidence of respiratory disease, prophylactic roentgen treatments were discontinued. These authors did not observe any cases of neoplasia in their follow-up study, which, however, included only one third of the cases and lasted only a few years for each child. Material Our 1,722 treated cases were taken from the records of three hospitals and from one pediatric and two radiological practices. The majority came from western New York and the rest from the State of Washington.

IMPORTANCE: Observational studies demonstrate links between patient-centered communication, quality of life (QOL), and aggressive treatments in advanced cancer, yet few randomized clinical trials (RCTs) of communication interventions have been reported. OBJECTIVE: To determine whether a combined intervention involving oncologists, patients with advanced cancer, and caregivers would promote patient-centered communication, and to estimate intervention effects on shared understanding, patient-physician relationships, QOL, and aggressive treatments in the last 30 days of life. DESIGN, SETTING, AND PARTICIPANTS: Cluster RCT at community- and hospital-based cancer clinics in Western New York and Northern California; 38 medical oncologists (mean age 44.6 years; 11 (29%) female) and 265 community-dwelling adult patients with advanced nonhematologic cancer participated (mean age, 64.4 years, 146 [55.0%] female, 235 [89%] white; enrolled August 2012 to June 2014; followed for 3 years); 194 patients had participating caregivers. INTERVENTIONS: Oncologists received individualized communication training using standardized patient instructors while patients received question prompt lists and individualized communication coaching to identify issues to address during an upcoming oncologist visit. Both interventions focused on engaging patients in consultations, responding to emotions, informing patients about prognosis and treatment choices, and balanced framing of information. Control participants received no training. MAIN OUTCOMES AND MEASURES: The prespecified primary outcome was a composite measure of patient-centered communication coded from audio recordings of the first oncologist visit following patient coaching (intervention group) or enrollment (control). Secondary outcomes included the patient-physician relationship, shared understanding of prognosis, QOL, and aggressive treatments and hospice use in the last 30 days of life. RESULTS: Data from 38 oncologists (19 randomized to intervention) and 265 patients (130 intervention) were analyzed. In fully adjusted models, the intervention resulted in clinically and statistically significant improvements in the primary physician-patient communication end point (adjusted intervention effect, 0.34; 95% CI, 0.06-0.62; P = .02). Differences in secondary outcomes were not statistically significant. CONCLUSIONS AND RELEVANCE: A combined intervention that included oncologist communication training and coaching for patients with advanced cancer was effective in improving patient-centered communication but did not affect secondary outcomes. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01485627.

Free-tissue transfers have become the preferred surgical technique to treat complex reconstructive defects. Because these procedures typically require longer operative times and recovery periods, the applicability of free-flap reconstruction in the elderly continues to require ongoing review. The authors performed a retrospective analysis of 100 patients aged 65 years and older who underwent free-tissue transfers to determine preoperative and intraoperative predictors of surgical complications, medical complications, and reconstructive failures. The parameters studied included patient demographics, past medical history, American Society of Anesthesiology (ASA) status, site and cause of the defect, the free tissue transferred, operative time, and postoperative complications, including free-flap success or failure. The mean age of the patients was 72 years. A total of 46 patients underwent free-tissue transfer after head and neck ablation, 27 underwent lower extremity reconstruction in the setting of peripheral vascular disease, 10 had lower extremity traumatic wounds, nine had breast reconstructions, four had infected wounds, two had chronic wounds, and two underwent transfer for lower extremity tumor ablation. Two patients had an ASA status of 1, 49 patients had a status of 2, 45 patients had a status of 3, and four had a status of 4. A total of 104 flaps were transferred in these 100 patients. There were 49 radial forearm flaps, 34 rectus abdominis flaps, seven latissimus dorsi flaps, seven fibular osteocutaneous flaps, three omental flaps, three jejunal flaps, and one lateral arm flap. Four patients had planned double free flaps for their reconstruction. Mean operative time was 7.8 hours (range, 3.5 to 16.5 hours). The overall flap success rate was 97 percent, and the overall reconstructive success rate was 92 percent. There were six additional reconstructive failures related to flap loss, all of which occurred more than 1 month after surgery. Patients with a higher ASA designation experienced more medical complications (p = 0.03) but not surgical complications. Increased operative time resulted in more surgical complications (p = 0.019). All eight cases of reconstructive failure occurred in patients undergoing limb salvage surgery in the setting of peripheral vascular disease. Free-tissue transfer in the elderly population demonstrates similar success rates to those of the general population. Age alone should not be considered a contraindication or an independent risk factor for free-tissue transfer. ASA status and length of operative time are significant predictors of postoperative medical and surgical morbidity. The higher rate of reconstructive failure in the elderly peripheral vascular disease population compares favorably with other treatment modalities for this disease process.

Exosomes are 30-150nM membrane-bound secreted vesicles that are readily isolated from biological fluids such as urine (UEs). Exosomes contain proteins, micro RNA (miRNA), messenger RNA (mRNA), and long non-coding RNA (lncRNA) from their cells of origin. Although miRNA, protein and lncRNA have been isolated from serum as potential biomarkers for benign and malignant disease, it is unknown if lncRNAs in UEs from urothelial bladder cancer (UBC) patients can serve as biomarkers. lncRNAs are > 200 nucleotide long transcripts that do not encode protein and play critical roles in tumor biology. As the number of recognized tumor-associated lncRNAs continues to increase, there is a parallel need to include lncRNAs into biomarker discovery and therapeutic target algorithms. The lncRNA HOX transcript antisense RNA (HOTAIR) has been shown to facilitate tumor initiation and progression and is associated with poor prognosis in several cancers. The importance of HOTAIR in cancer biology has sparked interest in using HOTAIR as a biomarker and potential therapeutic target. Here we show HOTAIR and several tumor-associated lncRNAs are enriched in UEs from UBC patients with high-grade muscle-invasive disease (HGMI pT2-pT4). Knockdown of HOTAIR in UBC cell lines reduces in vitro migration and invasion. Importantly, loss of HOTAIR expression in UBC cell lines alters expression of epithelial-to-mesenchyme transition (EMT) genes including SNAI1, TWIST1, ZEB1, ZO1, MMP1 LAMB3, and LAMC2. Finally, we used RNA-sequencing to identify four additional lncRNAs enriched in UBC patient UEs. These data, suggest that UE-derived lncRNA may potentially serve as biomarkers and therapeutic targets.

This is one of a series of studies being made to investigate the relationship of “separation and depression” to the onset of medical disease. In this report a group of 42 semiprivate hospitalized medical patients between the ages of 18 and 45 was studied for predisease setting based on reported object-relationship changes and reported and observed major affective reactions to such changes. Twenty-nine patients and/or family members reported loss of an object and feelings of helplessness and hopelessness immediately preceding the onset of the symptoms of the illness which led to hospitalization. Five patients reported feelings of helplessness or hopelessness prior to the onset of symptoms but reported no loss of an object. In 41 of the 42 patients the investigator felt that there was verbal and/or nonverbal evidence for the interpretation of actual, threatened, or symbolic object loss as well as evidence for feelings of helplessness or hopelessness prior to the onset of disease. Thirty-one patients developed the onset of their disease within one week after what was considered the final or only change in relationship to which the patient experienced a feeling of helplessness or hopelessness. Early life losses or threats of loss, past conflicts reawakened or still unresolved, and the incidence of past separations preceding changes in past health of this group of patients were also reported. "Separation and depression" as defined refers to the psychic pattern of unsuccessful resolution of object loss. Starting with a change in a relationship, this concept involves the actual or fantasied loss of an object upon which the self has real or symbolic dependence and includes the attempts and final failures to reestablish or give up the lost or threatened relationship, as evidenced by feelings of helplessness or hopelessness. Case examples are appended to illustrate how the setting of the current disease onset was reported and how the investigator made his interpretations of this material.

Two successive, 6-month, randomized, double-blind, controlled trials of prednisone showed that 0.75 mg/kg/d was the optimal dose to improve strength in boys with Duchenne muscular dystrophy (DMD). We attempted to maintain 93 boys on that dose for an additional 2 years. During the 3 years of observation, the decline in average muscle strength scores of all boys taking prednisone was 0.072 units/yr, as compared with an expected decline of 0.341 units/yr from natural history controls. The occurrence of side effects in some boys prevented maintenance of the full dose, which may have lessened the response. At the time of last visit, dosages ranged from 0.15 mg/kg to 0.75 mg/kg. In addition to maintaining their strength, several of the boys actually improved their performance in lifting kilogram weights and in some timed function tests. Treatment of DMD with prednisone significantly slows the progression of weakness and loss of function for at least 3 years.

PURPOSE OF REVIEW: This review presents our current understanding of the way metabolic acidosis induces calcium efflux from bone, and in the process, buffers additional systemic hydrogen ions associated with acidosis. RECENT FINDINGS: Acid-induced changes in bone mineral are consistent with a role for bone as a proton buffer. In response to metabolic acidosis in an in-vitro bone organ culture system, we observed a fall in mineral sodium, potassium, carbonate and phosphate, which each buffer protons and in vivo should increase systemic pH towards the physiologic normal. Initially, metabolic acidosis stimulates physicochemical mineral dissolution and subsequently cell-mediated bone resorption. Acidosis suppresses the activity of bone-resorbing cells, osteoblasts, decreasing gene expression of specific matrix proteins and alkaline phosphatase activity. There is concomitant acid stimulation of prostaglandin production by osteoblasts, which acting in a paracrine manner increases synthesis of the osteoblastic receptor activator of nuclear factor kappa B ligand (RANKL). The acid induction of RANKL then stimulates osteoclastic activity and recruitment of new osteoclasts to promote bone resorption and buffering of the proton load. Both the regulation of RANKL and acid-induced calcium efflux from bone are mediated by prostaglandins. SUMMARY: Metabolic acidosis, which occurs during renal failure, renal insufficiency or renal tubular acidosis, results in decreased systemic pH and is associated with an increase in urine calcium excretion. The apparent protective function of bone to help maintain systemic pH, which has a clear survival advantage for mammals, will come partly at the expense of its mineral stores.

The Schatzker classification system for tibial plateau fractures is widely used by orthopedic surgeons to assess the initial injury, plan management, and predict prognosis. Many investigators have found that surgical plans based on plain radiographic findings were modified after preoperative computed tomography (CT) or magnetic resonance (MR) imaging. The Schatzker classification divides tibial plateau fractures into six types: lateral plateau fracture without depression (type I), lateral plateau fracture with depression (type II), compression fracture of the lateral (type IIIA) or central (type IIIB) plateau, medial plateau fracture (type IV), bicondylar plateau fracture (type V), and plateau fracture with diaphyseal discontinuity (type VI). Management of type I, II, and III fractures centers on evaluating and repairing the articular cartilage. The fracture-dislocation mechanism of type IV fractures increases the likelihood of injury to the peroneal nerve or popliteal vessels. In type V and VI fractures, the location of soft-tissue injury dictates the surgical approach and the degree of soft-tissue swelling dictates the timing of definitive surgery and the need for provisional stabilization with an external fixator. CT and MR imaging are more accurate than plain radiography for Schatzker classification of tibial plateau fractures, and use of cross-sectional imaging can improve surgical planning.