University Hospitals Parma Medical Center

BACKGROUND: Brigatinib, a next-generation anaplastic lymphoma kinase (ALK) inhibitor, has robust efficacy in patients with ALK-positive non-small-cell lung cancer (NSCLC) that is refractory to crizotinib. The efficacy of brigatinib, as compared with crizotinib, in patients with advanced ALK-positive NSCLC who have not previously received an ALK inhibitor is unclear. METHODS: In an open-label, phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with advanced ALK-positive NSCLC who had not previously received ALK inhibitors to receive brigatinib at a dose of 180 mg once daily (with a 7-day lead-in period at 90 mg) or crizotinib at a dose of 250 mg twice daily. The primary end point was progression-free survival as assessed by blinded independent central review. Secondary end points included the objective response rate and intracranial response. The first interim analysis was planned when approximately 50% of 198 expected events of disease progression or death had occurred. RESULTS: A total of 275 patients underwent randomization; 137 were assigned to brigatinib and 138 to crizotinib. At the first interim analysis (99 events), the median follow-up was 11.0 months in the brigatinib group and 9.3 months in the crizotinib group. The rate of progression-free survival was higher with brigatinib than with crizotinib (estimated 12-month progression-free survival, 67% [95% confidence interval {CI}, 56 to 75] vs. 43% [95% CI, 32 to 53]; hazard ratio for disease progression or death, 0.49 [95% CI, 0.33 to 0.74]; P<0.001 by the log-rank test). The confirmed objective response rate was 71% (95% CI, 62 to 78) with brigatinib and 60% (95% CI, 51 to 68) with crizotinib; the confirmed rate of intracranial response among patients with measurable lesions was 78% (95% CI, 52 to 94) and 29% (95% CI, 11 to 52), respectively. No new safety concerns were noted. CONCLUSIONS: Among patients with ALK-positive NSCLC who had not previously received an ALK inhibitor, progression-free survival was significantly longer among patients who received brigatinib than among those who received crizotinib. (Funded by Ariad Pharmaceuticals; ALTA-1L ClinicalTrials.gov number, NCT02737501 .).

BACKGROUND: Inflammation is an important component of ischemic heart disease. PTX3 is a long pentraxin whose expression is induced by cytokines in endothelial cells, mononuclear phagocytes, and myocardium. The possibility that PTX3 is altered in patients with acute myocardial infarction (AMI) has not yet been tested. METHODS AND RESULTS: Blood samples were collected from 37 patients admitted to the coronary care unit (CCU) with symptoms of AMI. PTX3 plasma concentrations, as measured by ELISA, higher than the mean+2 SD of age-matched controls (2.01 ng/mL) were found in 27 patients within the first 24 hours of CCU admission. PTX3 peaked at 7.5 hours after CCU admission, and mean peak concentration was 6.94+/-11.26 ng/mL. Plasma concentrations of PTX3 returned to normal in all but 3 patients at hospital discharge and were unrelated to AMI site or extent, Killip class at entry, hours from symptom onset, and thrombolysis. C-reactive protein peaked in plasma at 24 hours after CCU admission, much later than PTX3 (P<0.001). Patients >64 years old and women had significantly higher PTX3 concentrations at 24 hours (P<0.05). PTX3 was detected by immunohistochemistry in normal but not in necrotic myocytes. CONCLUSIONS: PTX3 is present in the intact myocardium, increases in the blood of patients with AMI, and disappears from damaged myocytes. We suggest that PTX3 is an early indicator of myocyte irreversible injury in ischemic cardiomyopathy.

Abstract Laboratory diagnostics (i.e., the total testing process) develops conventionally through a virtual loop, originally referred to as "the brain to brain cycle" by George Lundberg. Throughout this complex cycle, there is an inherent possibility that a mistake might occur. According to reliable data, preanalytical errors still account for nearly 60%-70% of all problems occurring in laboratory diagnostics, most of them attributable to mishandling procedures during collection, handling, preparing or storing the specimens. Although most of these would be "intercepted" before inappropriate reactions are taken, in nearly one fifth of the cases they can produce inappropriate investigations and unjustifiable increase in costs, while generating inappropriate clinical decisions and causing some unfortunate circumstances. Several steps have already been undertaken to increase awareness and establish a governance of this frequently overlooked aspect of the total testing process. Standardization and monitoring preanalytical variables is of foremost importance and is associated with the most efficient and well-organized laboratories, resulting in reduced operational costs and increased revenues. As such, this article is aimed at providing readers with significant updates on the total quality management of the preanalytical phase to endeavour further improvement for patient safety throughout this phase of the total testing process.

BACKGROUND: This prospective, randomized, blinded study tested the hypothesis that ultrasound guidance can shorten the onset time of axillary brachial plexus block as compared with nerve stimulation guidance when using a multiple injection technique. METHODS: Sixty American Society of Anesthesiology physical status I-III patients receiving axillary brachial plexus block with 20 ml ropivacaine, 0.75%, using a multiple injection technique, were randomly allocated to receive either nerve stimulation (group NS, n = 30), or ultrasound guidance (group US, n = 30) for nerve location. A blinded observer recorded the onset of sensory and motor blocks, the need for general anesthesia (failed block) or greater than 100 microg fentanyl (insufficient block) to complete surgery, procedure-related pain, success rate, and patient satisfaction. RESULTS: The median (range) number of needle passes was 4 (3-8) in group US and 8 (5-13) in group NS (P = 0.002). The onset of sensory block was shorter in group US (14 +/- 6 min) than in group NS (18 +/- 6 min) (P = 0.01), whereas no differences were observed in onset of motor block (24 +/- 8 min in group US and 25 +/- 8 min in group NS; P = 0.33) and readiness to surgery (26 +/- 8 min in group US and 28 +/- 9 min in group NS; P = 0.48). No failed block was reported in either group. Insufficient block was observed in 1 patient (3%) of group US and 2 patients (6%) of group NS (P = 0.61). Procedure-related pain was reported in 6 patients (20%) of group US and 14 patients (48%) of group NS (P = 0.028); patient acceptance was similarly good in the two groups. CONCLUSION: Multiple injection axillary block with ultrasound guidance provided similar success rates and comparable incidence of complication as compared with nerve stimulation guidance.

In this review, we overview the main features and functions of NK cells, focusing on their role in cell-mediated immune response to tumor cells. In parallel, we discuss the information available in the field of NK cell receptors and offer a wide general overview of functional aspects of cell targeting and killing, focusing on the recent acknowledgments on the efficacy of NK cells after cytokine and mAb administration in cancer therapy. Since efficacy of NK cell-based immunotherapy has been proven in KIR-mismatch regimens or in TRAIL-dependent apoptosis, the ability to manipulate the balance of activating and inhibitory receptors on NK cells and of their cognate ligands, as well as the sensitivity of tumor cells to apoptosis, opens new perspectives for NK cell-based immunotherapy.

BACKGROUND: Malnutrition is common in hospitalized older people and may predict adverse outcomes. Previous studies of the relationship between nutritional status and hospital outcomes are limited by inadequate accounting for other potential predictors of adverse outcomes, the failure to consider functional outcomes, and the omission of clinical assessments of nutritional status. OBJECTIVE: To measure the relationship between a clinical assessment of nutritional status on hospital admission and subsequent mortality, functional dependence, and nursing home use. DESIGN: Prospective cohort study SETTING: A tertiary care hospital PATIENTS: A total of 369 patients at least 70 years old (mean age 80.3, 62% women) admitted to a general medical service MEASUREMENTS: Nutritional status was measured with the Subjective Global Assessment, a validated measure of nutritional status based on historical and physical exam findings. Patients were classified as severely malnourished (generally at least a 10% weight loss over the previous 6 months and marked physical signs of malnutrition), moderately malnourished (generally a 5 to 10% weight loss and moderate physical signs), or well nourished. Vital status, independence in activities of daily living, and nursing home use were determined through patient or surrogate interview at admission and 90 days and 1 year after discharge. Indices of comorbidity and illness severity were determined from chart review. RESULTS: 219 patients (59.3%) were well nourished, 90 (24.4%) were moderately malnourished, and 60 (16.3%) were severely malnourished. Severely malnourished patients were more likely than moderately malnourished or well nourished patients to die by 90 days (31.7%, 23.3%, and 12.3%, respectively, P < .001) and 1 year (55.0%, 35.6%, and 27.9%, P < .001) after discharge. In logistic regression models controlling for acute illness severity, comorbidity, and functional status on admission, severely malnourished patients were more likely than well nourished patients to die within 1 year of discharge (OR = 2.83, 95% CI, 1.47-5.45), to be dependent in activities of daily living 3 months after discharge (OR = 2.81, 1.06-7.46), and to spend time in a nursing home during the year after discharge (OR = 3.22, 1.05-9.87). CONCLUSION: Malnutrition was common in hospitalized patients with medical illness and was associated with greater mortality, delayed functional recovery, and higher rates of nursing home use. These adverse outcomes were not explained by greater acute illness severity, comorbidity, or functional dependence in malnourished patients on hospital admission.

This report describes the clinical, laboratory, and epidemiological findings on 27 cases of Mayaro virus (MV) disease, an emerging mosquito-borne viral illness that is endemic in rural areas of tropical South America. MV disease is a nonfatal, dengue-like illness characterized by fever, chills, headache, eye pain, generalized myalgia, arthralgia, diarrhea, vomiting, and rash of 3-5 days' duration. Severe joint pain is a prominent feature of this illness; the arthralgia sometimes persists for months and can be quite incapacitating. Cases of two visitors from the United States, who developed MV disease during visits to eastern Peru, are reported. MV disease and dengue are difficult to differentiate clinically.

An association between hyperinsulinemia and hypertension has been suggested by epidemiological surveys. To assess whether this association is independent of the presence of other hyperinsulinemic states, such as obesity and glucose intolerance, we measured the insulin response to oral glucose in a group of middle-aged moderately obese [144 +/- 4% overweight (mean +/- SEM)] patients (n = 18) with essential hypertension (174 +/- 5/104 +/- 2 mm Hg) and normal glucose tolerance. Normotensive subjects (n = 17) with normal glucose tolerance, matched for age and degree of overweight, served as the control group. The mean insulin response to glucose was twice as high in the hypertensive patients (25.8 +/- 0.2 mU/ml X 2 h) as in the normotensive subjects (11.3 +/- 0.2; P less than 0.001), yet the glucose incremental area was 3-fold higher in the former (10.9 +/- 1.0 g/dl X 2 h) than in the latter (3.5 +/- 0.7; P less than 0.001), thus indicating more severe insulin resistance. In the hypertensive group, systolic blood pressure levels were directly correlated with the 2-h plasma insulin values (r = 0.75; P less than 0.001). Furthermore, the 2-h plasma insulin value and the degree of overweight accounted for 65% of the variation in the systolic blood pressure in a multiple regression model (r = 0.81; P less than 0.001). We conclude that in obesity, the occurrence of hypertension marks the presence of additional hyperinsulinemia and insulin resistance, independent of any impairment of glucose tolerance.

BACKGROUND: Postoperative shoulder-tip pain occurs frequently following laparoscopic cholecystectomy. The aim of this randomized clinical trial was to evaluate the efficacy of a low-pressure carbon dioxide pneumoperitoneum during laparoscopic surgery in reducing the incidence of postoperative shoulder-tip pain. METHODS: Ninety consecutive patients undergoing laparoscopic cholecystectomy were randomized prospectively into low-pressure (group A) and normal-pressure (group B) laparoscopic cholecystectomy groups. Patients in group A (n = 46) underwent laparoscopic cholecystectomy with 9 mmHg carbon dioxide pneumoperitoneum during most of the operation, and those in group B (n = 44) had laparoscopic cholecystectomy with 13 mmHg pneumoperitoneum. Shoulder-tip pain was recorded on a visual analogue pain scale 1, 3, 6, 12, 24 and 48 h after operation. RESULTS: The low-pressure pneumoperitoneum did not increase the duration of surgery. There were no significant intraoperative or postoperative complications in either group. Fourteen patients (32 per cent) in group B and five (11 per cent) in group A complained of shoulder pain (P<0.05). Mean shoulder-tip pain scores at 12 and 24 h and postoperative analgesia requirements were also significantly lower in the low-pressure laparoscopic cholecystectomy group (P<0.001). CONCLUSION: A carbon dioxide pneumoperitoneum pressure lower than that usually utilized to perform laparoscopic surgery reduces both the frequency and intensity of shoulder-tip pain following laparoscopic cholecystectomy.

BACKGROUND AND PURPOSE: Physical deconditioning is involved in the impaired exercise tolerance of patients with multiple sclerosis (MS), but data on the effects of aerobic training (AT) in this population are scanty. The purpose of this study was to compare the effects of an 8-week AT program on exercise capacity-in terms of walking capacity and maximum exercise tolerance, as well as its effects on fatigue and health-related quality of life-as compared with neurological rehabilitation (NR) in subjects with MS. SUBJECTS AND METHODS: Nineteen subjects (14 female, 5 male; mean age [X+/-SD]=41+/-8 years) with mild to moderate disability secondary to MS participated in a randomized crossover controlled study. Eleven subjects (8 female, 3 male; mean age [X+/-SD]=44+/-6 years) completed the study. RESULTS: After AT, but not NR, the subjects' walking distances and speeds during a self-paced walk were significantly improved, as were their maximum work rate, peak oxygen uptake, and oxygen pulse during cardiopulmonary exercise tests. The increases in peak oxygen uptake and maximum work rate, but not in walking capacity, were significantly higher after AT, as compared with after NR. Additionally, the subjects who were most disabled tended to benefit more from AT. There were no differences between AT and NR in effects on fatigue, and the results showed that AT may have partially affected health-related quality of life. DISCUSSION AND CONCLUSION: The results suggest that AT is more effective than NR in improving maximum exercise tolerance and walking capacity in people with mild to moderate disability secondary to MS.

A progressive, systemic, and low-grade proinflammatory status is one of the major characteristics of immunosenescence. Emerging data suggest a possible contribution of CMV, known to chronically infect a large proportion of humans, lifelong from newborns to centenarians. To test this hypothesis, we evaluated functional T cell responses to two CMV immunogenic proteins, pp65 and IE-1, in 65 chronically infected subjects aged 25-100 years. PBMC were stimulated with mixtures of peptides spanning the entire sequence of both proteins, and Ag specificity and magnitude of intracellular IFN-gamma- and TNF-alpha-positive cells were then analyzed within both CD4+ and CD8+ T cells. Results indicate that pp65 and, to a lesser extent, IE-1 constitute major Ags against which aged people target functionally efficient T cell effector responses with massive production of Th1 cytokines and exhibition of CD107a degranulation marker. As a result, the production of IFN-gamma induced in T cells by both Ags was seven to eight times greater in very old than in young subjects. The comparative analysis of pp65-specific responses in these very long-term carriers revealed a reciprocal relationship between CD4+ and CD8+ producing IFN-gamma in the same individuals. These results indicate that CMV represents an important pathogen responsible for a strong immune activation in human aging. Such a remarkable burden of effector CD4+ and CD8+ T cells may be necessary to protect the elderly from CMV endogenous reactivation, but can turn detrimental by giving a substantial contribution to the proinflammatory status that accompanies the main age-related diseases.

OBJECTIVE: To determine the usefulness of ultrasound to evaluate central venous catheter misplacements and detection of pneumothorax, thus obviating postprocedural radiograph. After the insertion of a central venous catheter, chest radiograph is usually obtained to ensure correct positioning of the catheter tip and detect postprocedural complications. DESIGN: Prospective observational study. SETTING: Adult intensive care unit. PATIENTS: 111 consecutive patients undergoing central venous catheter positioning, using a landmark technique and contrast-enhanced ultrasonography. MEASUREMENTS AND MAIN RESULTS: A postprocedural chest radiograph was obtained for all patients and was considered as a reference technique. At the end of the procedure, a B-mode ultrasonography was first performed to assess catheter position and detect pneumothorax. Right atrium positioning was detected in 19 patients by ultrasonography, and an additional six by contrast enhanced ultrasonography. Combining ultrasonography and contrast enhanced ultrasonography yielded a 96% sensitivity and 93% specificity in detecting catheter misplacement. Concordance was 95% and kappa value was 0.88 (p < .001). Pneumothorax was detected in four patients by ultrasonography and in two by chest radiograph (concordance = 98%). The mean time required to perform ultrasonography plus contrast enhanced ultrasonography was 10 +/- 5 mins vs. 83 +/- 79 mins for chest radiograph (p < .05). CONCLUSIONS: The close concordance between ultrasonography plus contrast enhanced ultrasonography and chest radiograph justifies the use of sonography as a standard technique to ensure the correct positioning of the catheter tip and to detect pneumothorax after central venous catheter cannulation to optimize use of hospital resources and minimize time consumption and radiation. Chest radiograph will be necessary when sonographic examination is impossible to perform by technical limitations.

BACKGROUND: The activation of B(2) receptors by kinins could exert cardioprotective effects in myocardial ischemia and heart failure. METHODS AND RESULTS: To test whether the absence of bradykinin B(2) receptors may affect cardiac structure and function, we examined the developmental changes in blood pressure (BP), heart rate, and heart morphology of bradykinin B(2) receptor gene knockout (B(2)(-/-)), heterozygous (B(2)(+/-)), and wild-type (B(2)(+/+)) mice. The BP of B(2)(-/-) mice, which was still normal at 50 days of age, gradually increased, reaching a plateau at 6 months (136+/-3 versus 109+/-1 mm Hg in B(2)(+/+), P<0.01). In B(2)(+/-) mice, BP elevation was delayed. At 40 days, the heart rate was higher (P<0.01) in B(2)(-/-) and B(2)(+/-) than in B(2)(+/+) mice, whereas the left ventricular (LV) weight and chamber volume were similar among groups. Thereafter, the LV growth rate of B(2)(-/-) and B(2)(+/-) mice was accelerated, leading at 360 days to a LV weight-to-body weight ratio that was 9% and 17% higher, respectively, than that of B(2)(+/+) mice. In B(2)(-/-) mice, hypertrophy was associated with a marked chamber dilatation (42% larger than that of B(2)(+/+) mice), an elevation in LV end-diastolic pressure (25+/-3 versus 5+/-1 mm Hg in B(2)(+/+) mice, P<0.01), and reparative fibrosis. CONCLUSIONS: The disruption of the bradykinin B(2) receptor leads to hypertension, LV remodeling, and functional impairment, implying that kinins are essential for the functional and structural preservation of the heart.

OBJECTIVES: Most physiological indicators of bipolar disorder (BPD) reflect current acute illness, and rarely have proved to be state-independent. Activity rhythms are highly abnormal in acute phases of BPD; we compared circadian activity rhythms in BPD I patients during ill and recovered states to those of normal controls to test the hypothesis that some abnormalities may persist. METHODS: We compared 36 adult DSM-IV BPD I patients during acute mania or mixed states, and during full and sustained clinical recovery, to 32 healthy controls of similar age and sex distribution, using wrist-worn, piezoelectric actigraphic monitoring for 72 h and computed cosinor analysis of circadian activity rhythms. RESULTS: We verified expected major differences between manic or mixed-state BPD I patients and matched normal controls, including phase advances averaging 2.1 h in ill BPD I patients and 1.8 h in recovered patients. Moreover, recovered BPD patients differed highly significantly from controls in several measures, including acrophase advance, higher percentage of nocturnal sleep, and lower average daily activity (mesor). Actigraphic measures among recovered BPD patients were independent of ratings of mania (on the Young Mania Rating Scale), depression (on the Hamilton Depression Rating Scale), or rating-scale scored subjective distress, as well as the type and dose of concurrent psychotropic medication. CONCLUSIONS: These findings suggest that abnormal activity rhythms, including sustained phase advances, may represent enduring (trait) characteristics of BPD patients even during clinical recovery. If verified, such indices may be useful in supporting diagnoses and as an objective phenotype for genetic or other biological studies.

Deficiencies of antithrombin (AT), protein C (PC) or protein S (PS), and activated protein C resistance (APCR) are very well-established coagulation defects predisposing to venous thromboembolism (VTE). We performed a retrospective cohort family study to assess the risk for VTE in individuals with AT, PC, or PS deficiency, or APCR. Five hundred thirteen relatives from 9 Italian centers were selected from 233 families in which the proband had had at least 1 episode of VTE. We calculated the incidence of VTE in the whole cohort and in the subgroups after stratification by age, sex, and defect. The overall incidence of VTE (per 100 patient-years) in the group of relatives was 0.52. It was 1.07 for AT, 0.54 for PC, 0.50 for PS, 0.30 for APCR, and 0.67 in the group with a double defect. The incidence was associated with age, but not with sex. The mean age at onset was between 30 and 40 years for all the coagulation defects. Women had the peak of incidence in the age range of 21 to 40 years, earlier than men. The lifetime risk for VTE was 4.4 for AT versus APCR, 2.6 for AT versus PS, 2.2 for AT versus PC, 1.9 for PC versus APCR, and 1.6 for PS versus APCR. AT deficiency seems to have a higher risk for VTE than the other genetic defects. There is a relation between age and occurrence of thrombosis for both men and women. The latter had the peak of incidence earlier than the former.

Laboratory diagnostics develop through different phases that span from test ordering (pre-preanalytical phase), collection of diagnostic specimens (preanalytical phase), sample analysis (analytical phase), results reporting (postanalytical phase) and interpretation (post-postanalytical phase). Although laboratory medicine seems less vulnerable than other clinical and diagnostic areas, the chance of errors is not negligible and may adversely impact on quality of testing and patient safety. This article, which continues a biennial tradition of collective papers on preanalytical quality improvement, is aimed to provide further contributions for pursuing quality and harmony in the preanalytical phase, and is a synopsis of lectures of the third European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)-Becton Dickinson (BD) European Conference on Preanalytical Phase meeting entitled 'Preanalytical quality improvement. In pursuit of harmony' (Porto, 20-21 March 2015). The leading topics that will be discussed include unnecessary laboratory testing, management of test request, implementation of the European Union (EU) Directive on needlestick injury prevention, harmonization of fasting requirements for blood sampling, influence of physical activity and medical contrast media on in vitro diagnostic testing, recent evidence about the possible lack of necessity of the order of draw, the best practice for monitoring conditions of time and temperature during sample transportation, along with description of problems emerging from inappropriate sample centrifugation. In the final part, the article includes recent updates about preanalytical quality indicators, the feasibility of an External Quality Assessment Scheme (EQAS) for the preanalytical phase, the results of the 2nd EFLM WG-PRE survey, as well as specific notions about the evidence-based quality management of the preanalytical phase.

BACKGROUND: There are a lack of randomized controlled trial data comparing outcomes of different catheter-based interventions for intermediate-risk pulmonary embolism. METHODS: PEERLESS is a prospective, multicenter, randomized controlled trial that enrolled 550 patients with intermediate-risk pulmonary embolism with right ventricular dilatation and additional clinical risk factors randomized 1:1 to treatment with large-bore mechanical thrombectomy (LBMT) or catheter-directed thrombolysis (CDT). The primary end point was a hierarchal win ratio composite of the following (assessed at the sooner of hospital discharge or 7 days after the procedure): (1) all-cause mortality, (2) intracranial hemorrhage, (3) major bleeding, (4) clinical deterioration and/or escalation to bailout, and (5) postprocedural intensive care unit admission and length of stay. Assessments at the 24-hour visit included respiratory rate, modified Medical Research Council dyspnea score, New York Heart Association classification, right ventricle/left ventricle ratio reduction, and right ventricular function. End points through 30 days included total hospital stay, all-cause readmission, and all-cause mortality. RESULTS: The primary end point occurred significantly less frequently with LBMT compared with CDT (win ratio, 5.01 [95% CI, 3.68–6.97]; P &lt;0.001). There were significantly fewer episodes of clinical deterioration and/or bailout (1.8% versus 5.4%; P =0.04) with LBMT compared with CDT and less postprocedural intensive care unit use ( P &lt;0.001), including admissions (41.6% versus 98.6%) and stays &gt;24 hours (19.3% versus 64.5%). There were no significant differences in mortality, intracranial hemorrhage, or major bleeding between strategies or in a secondary win ratio end point including the first 4 components (win ratio, 1.34 [95% CI, 0.78–2.35]; P =0.30). At the 24-hour visit, respiratory rate was lower for patients treated with LBMT (18.3±3.3 versus 20.1±5.1; P &lt;0.001), and fewer had moderate to severe modified Medical Research Council dyspnea scores (13.5% versus 26.4%; P &lt;0.001), New York Heart Association classifications (16.3% versus 27.4%; P =0.002), and right ventricular dysfunction (42.1% versus 57.9%; P =0.004). Right ventricle/left ventricle ratio reduction was similar (0.32±0.24 versus 0.30±0.26; P =0.55). Patients treated with LBMT had shorter total hospital stays (4.5±2.8 overnights versus 5.3±3.9 overnights; P =0.002) and fewer all-cause readmissions (3.2% versus 7.9%; P =0.03), whereas 30-day mortality was similar (0.4% versus 0.8%; P =0.62). CONCLUSIONS: PEERLESS met its primary end point in favor of LBMT compared with CDT in treatment of intermediate-risk pulmonary embolism. LBMT had lower rates of clinical deterioration and/or bailout and postprocedural intensive care unit use compared with CDT, with no difference in mortality or bleeding. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05111613.

BACKGROUND: There is long-standing disagreement among facial plastic surgeons as to the ideal suture material for closing skin wounds of the face. Many surgeons believe that nonabsorbable suture material is preferable, as it is easier to tie, is unlikely to break prematurely, and elicits a minimal inflammatory response. Others feel that these issues are of minor importance and prefer absorbable sutures because they do not have to be removed, thus saving the surgeon time and decreasing patient anxiety and discomfort. PATIENTS AND METHODS: Facial skin cancers were removed from 41 patients. The length of closure ranged from 3.5 to 12.0 cm. All wounds were closed with rotational advancement flaps. Deep tissues were closed with 4-0 poliglecaprone 25 (Monocryl; Ethicon Inc, Somerville, NJ). One half of each wound was randomly closed with 5-0 coated polypropylene (Prolene; Ethicon Inc), while the other half was closed with 5-0 coated irradiated polyglactin 910 (Vicryl Rapide; Ethicon Inc). No wound infections or premature rupture of sutures occurred. All patients were followed up for 6 months after surgery. The photographs of the results were reviewed, and no difference was noted in scar formation. CONCLUSIONS: In adults with clean wounds of the face or neck, there is no difference in long-term cosmetic results of repairs with permanent or absorbable suture material. We prefer absorbable sutures, as they do not have to be removed, saving the surgeon time and lessening patient anxiety and discomfort.

Between 1986 and 1994, 13 patients with mobile painful arthritic elbows were treated by distraction interposition arthroplasty using fascia lata. The mean period of follow-up was 63 months. An elbow distractor/fixator was applied for three to four weeks to separate the articular surfaces and to protect the fascial graft. Nine of the 13 patients (69%) had satisfactory relief from pain; eight (62%) had an excellent or good result by the objective criteria of the Mayo Elbow Performance score. Four have required revision to total elbow arthroplasty at a mean of 30 months with good results to date. Instability of the elbow, both before and after surgery, was found to be associated with unsatisfactory results. The rate of success when the procedure was performed for inflammatory arthritis was similar to that for post-traumatic arthritis, about 67%. Eight complications occurred in six patients, all in the group with post-traumatic arthritis. Two of these required further surgical procedures such as transposition of the ulnar nerve or repair of hernia of the fascia lata. Although less reliable than prosthetic replacement, distraction interposition arthroplasty is a useful option in the treatment of young, high-demand patients with arthritis of the elbow. It is rarely indicated in the presence of generalised inflammatory arthritis, but may be of value in those patients in whom the disease is limited primarily to the elbow.

Since the 2009 publication of the stress echocardiography expert consensus of the European Association of Echocardiography, and after the 2016 advice of the American Society of Echocardiography-European Association of Cardiovascular Imaging for applications beyond coronary artery disease, new information has become available regarding stress echo. Until recently, the assessment of regional wall motion abnormality was the only universally practiced step of stress echo. In the state-of-the-art ABCDE protocol, regional wall motion abnormality remains the main step A, but at the same time, regional perfusion using ultrasound-contrast agents may be assessed. Diastolic function and pulmonary B-lines are assessed in step B; left ventricular contractile and preload reserve with volumetric echocardiography in step C; Doppler-based coronary flow velocity reserve in the left anterior descending coronary artery in step D; and ECG-based heart rate reserve in non-imaging step E. These five biomarkers converge, conceptually and methodologically, in the ABCDE protocol allowing comprehensive risk stratification of the vulnerable patient with chronic coronary syndromes. The present document summarizes current practice guidelines recommendations and training requirements and harmonizes the clinical guidelines of the European Society of Cardiology in many diverse cardiac conditions, from chronic coronary syndromes to valvular heart disease. The continuous refinement of imaging technology and the diffusion of ultrasound-contrast agents improve image quality, feasibility, and reader accuracy in assessing wall motion and perfusion, left ventricular volumes, and coronary flow velocity. Carotid imaging detects pre-obstructive atherosclerosis and improves risk prediction similarly to coronary atherosclerosis. The revolutionary impact of artificial intelligence on echocardiographic image acquisition and analysis makes stress echo more operator-independent and objective. Stress echo has unique features of low cost, versatility, and universal availability. It does not need ionizing radiation exposure and has near-zero carbon dioxide emissions. Stress echo is a convenient and sustainable choice for functional testing within and beyond coronary artery disease.