Forearm Muscle Activity During the Handgrip Test in Breast Cancer Survivors: A Cross-Sectional Study.

INTRODUCTION/BACKGROUND: Breast cancer survivors (BCS) frequently show upper limb dysfunctions. The forearm muscle activity measured by surface electromyography (sEMG) in this population has not been studied. This study aimed to describe forearm muscle activity in BCS, as well as to assess its possible relationship with other variables related to upper limb functionality and cancer-related fatigue (CRF). MATERIALS AND METHODS: A cross-sectional study was carried out including 102 BCS as volunteers at a secondary care in Malaga, Spain. BCS were included if they were aged between 32 and 70 years old, without evidence of cancer recurrence at the time of recruitment. The forearm muscle activity (microvolts, µV) was assessed by sEMG during the handgrip test. The handgrip strength was assessed by dynamometry (kg), the upper limb functionality (%) was measured by the upper limb functional index (ULFI) questionnaire and the CRF was also assessed by revised Piper Fatigue Scale (0-10 points). RESULTS: BCS reported reduced forearm muscle activity (287.88 µV) and reduced handgrip strength (21.31 Kg), a good upper limb functionality (68.85%), and a moderate cancer-related fatigue (4.74). Forearm muscle activity showed a poor significant correlation (r = -0.223, P = .038) with the CRF. Handgrip strength showed a poor correlation with the upper limb functionality (r = 0.387, P < .001) and age (r=-0.200, P = .047). CONCLUSION: BCS showed a reduced forearm muscle activity. BCS also presented a poor correlation between forearm muscle activity and handgrip strength. Both outcomes tended to lower values with higher levels of CRF, while preserving a good upper limb functionality.

The Benefits of a Therapeutic Exercise and Educational Intervention Program on Central Sensitization Symptoms and Pain-Related Fear Avoidance in Breast Cancer Survivors.

BACKGROUND: Central sensitization symptoms and pain-related fear avoidance are two common problems in breast cancer survivors. Non-pharmacologic interventions such as therapeutic exercise and patient education can be effective in this population. AIMS: This study aimed to: (1) analyze the benefits of a therapeutic exercise and educational program on central sensitization symptoms and pain-related fear avoidance in breast cancer survivors, and (2) explore the association between pain-related fear avoidance and central sensitization symptoms. DESIGN: A single group pre-post intervention study was conducted. METHODS: Patients were recruited from the service of Medical Oncology of the University Clinical Hospital Virgen de la Victoria, in Málaga (Spain). The intervention consisted of a therapeutic exercise and educational program that lasted 12 weeks, twice a week, for 1 hour. Two instruments were used: the Spanish version of the Central Sensitization Inventory and the Spanish Fear Avoidance Components Scale. RESULTS: A total of 82 breast cancer survivors participated in the study. Pre-post change on Central Sensitization Inventory was statistically significant (p = .007). There was a trend towards a significant difference for the Spanish Fear Avoidance Components Scale (p = .062). There was a statistically significant correlation between pain-related fear avoidance and central sensitization symptoms (r = 0.536, p < .001). CONCLUSIONS: The current study has provided preliminary evidence on the benefits of this intervention in pain-related fear avoidance and central sensitization symptoms in breast cancer survivors. The Spanish version of the Central Sensitization Inventory and the Spanish Fear Avoidance Components Scale demonstrated responsiveness to change.

Risk Prediction Tools Available for Germline BRCA1/2 Mutations Underperform in Prostate Cancer Patients.

Early identification of germline BRCA1/2 mutations may be relevant for the management of patients with prostate cancer (PC) and to prevent future breast and ovarian cancers in their relatives. Several prediction tools have been developed to estimate the likelihood of a germline BRCA1/2 mutation and are widely used to optimize screening in breast and ovarian cancer patients. We aimed to elucidate the proportion of PC patients with known BRCA1/2 mutations who would have qualified for testing using two risk calculation models (BRCAPRO and the Manchester scoring system [MSS]). We analyzed 106 families with known BRCA1/BRCA2 mutations, including 23 with PC cases. Only 30% and 48% of PC patients who were known BRCA1/BRCA2 mutations carriers would have qualified for testing using BRCAPRO and MSS, respectively. A median of two breast and/or ovarian cancer cases per family had occurred between the first PC identified in a carrier and the cancer case leading to germline testing. PATIENT SUMMARY: We tested two models developed to predict the probability of inherited BRCA1/BRCA2 mutations and found that these tools underperform in men with prostate cancer and should not be used to optimize testing in this population.

Single-Molecule Sequencing Reveals Patterns of Preexisting Drug Resistance That Suggest Treatment Strategies in Philadelphia-Positive Leukemias.

Purpose: Sequential treatment with targeted therapies can result in complex combinations of resistance mutations in drug targets. This mutational complexity has spurred the development of pan-target inhibitors, i.e., therapies for which no single target mutation can cause resistance. Because the propensity for on- versus off-target resistance varies across cancer types, a deeper understanding of the mutational burden in drug targets could rationalize treatment outcomes and prioritize pan-target inhibitors for indications where on-target mutations are most likely.Experimental Design: To measure and model the mutational landscape of a drug target at high resolution, we integrated single-molecule Duplex Sequencing of the ABL1 gene in Philadelphia-positive (Ph+) leukemias with computational simulations.Results: A combination of drug target mutational burden and tumor-initiating cell fraction is sufficient to predict that most patients with chronic myeloid leukemia are unlikely to harbor ABL1 resistance mutations at the time of diagnosis, rationalizing the exceptional success of targeted therapy in this setting. In contrast, our analysis predicts that many patients with Ph+ acute lymphoblastic leukemia (Ph+ ALL) harbor multiple preexisting resistant cells with single mutants. The emergence of compound mutations can be traced to initial use of an ABL1 inhibitor that is susceptible to resistance from single point mutations.Conclusions: These results argue that early use of therapies that achieve pan-inhibition of ABL1 resistance mutants might improve outcomes in Ph+ ALL. Our findings show how a deep understanding of the mutational burden in drug targets can be quantitatively coupled to phenotypic heterogeneity to rationalize clinical phenomena. Clin Cancer Res; 24(21); 5321-34. ©2018 AACR.

Efficacy and safety of weekly paclitaxel combined with cetuximab in the treatment of pretreated recurrent/metastatic head and neck cancer patients.

INTRODUCTION: The addition of cetuximab to weekly paclitaxel has demonstrated high efficacy in the first-line treatment of patients with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M-SCCHN). However, this combination has been widely extended to patients who present resistance to first line chemotherapy (CT) or those who are not candidates for platinum-based CT. MATERIAL AND METHODS: We have retrospectively analyzed the efficacy and safety of cetuximab in combination with weekly paclitaxel in patients with R/M-SCCHN who present disease progression after platinum schedules or those who were not candidates for platinum-based CT. Patients received weekly paclitaxel 80mg/m(2) and cetuximab 250mg/m(2) (initial dose of 400mg/m(2)) until progression or unacceptable toxicity. RESULTS: Twenty-two patients were included. Median age was 58 (43-68), ECOG PS (0/1/2): 6/10/4, 19 patients had received prior platinum-based treatment (nine patients were platinum-sensitive and nine were platinum-refractory). With a median follow-up of 6.18months (range 1.3-29.7), overall response rate (ORR) was 55% (95% CI 31-76%):1 (5%) complete response and 9 (50%) partial responses. Median duration of response was 10.23months. Median progression free survival (PFS) and overall survival (OS) were 5.4 and 9.1months, respectively. There were no differences in response rate according to platinum sensitivity (66% sensitive vs 44% refractory; P=0.61). The main toxicity consisted of rash in 70% of patients (5% grade 3), with an association between rash severity and ORR (grade 0-1: 33% vs grade 2-3: 64%; P=0.03) and a trend for better PFS and OS. CONCLUSION: Weekly paclitaxel in combination with cetuximab is a well tolerated and highly active second-line treatment in patients with R/MSCCHN who experience disease progression after platinum-based CT, including those who present resistant disease. Our results suggest that the efficacy of this combination is apparently superior than the published data on single agent cetuximab in this setting.

Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial.

BACKGROUND: The anti-CD52 monoclonal antibody alemtuzumab reduced disease activity in a phase 2 trial of previously untreated patients with relapsing-remitting multiple sclerosis. We aimed to assess efficacy and safety of first-line alemtuzumab compared with interferon beta 1a in a phase 3 trial. METHODS: In our 2 year, rater-masked, randomised controlled phase 3 trial, we enrolled adults aged 18-50 years with previously untreated relapsing-remitting multiple sclerosis. Eligible participants were randomly allocated in a 2:1 ratio by an interactive voice response system, stratified by site, to receive intravenous alemtuzumab 12 mg per day or subcutaneous interferon beta 1a 44 µg. Interferon beta 1a was given three-times per week and alemtuzumab was given once per day for 5 days at baseline and once per day for 3 days at 12 months. Coprimary endpoints were relapse rate and time to 6 month sustained accumulation of disability in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT00530348. FINDINGS: 187 (96%) of 195 patients randomly allocated interferon beta 1a and 376 (97%) of 386 patients randomly allocated alemtuzumab were included in the primary analyses. 75 (40%) patients in the interferon beta 1a group relapsed (122 events) compared with 82 (22%) patients in the alemtuzumab group (119 events; rate ratio 0·45 [95% CI 0·32-0·63]; p<0.0001), corresponding to a 54·9% improvement with alemtuzumab. Based on Kaplan-Meier estimates, 59% of patients in the interferon beta 1a group were relapse-free at 2 years compared with 78% of patients in the alemtuzumab group (p<0·0001). 20 (11%) of patients in the interferon beta 1a group had sustained accumulation of disability compared with 30 (8%) in the alemtuzumab group (hazard ratio 0·70 [95% CI 0·40-1·23]; p=0·22). 338 (90%) of patients in the alemtuzumab group had infusion-associated reactions; 12 (3%) of which were regarded as serious. Infections, predominantly of mild or moderate severity, occurred in 253 (67%) patients treated with alemtuzumab versus 85 (45%) patients treated with interferon beta 1a. 62 (16%) patients treated with alemtuzumab had herpes infections (predominantly cutaneous) compared with three (2%) patients treated with interferon beta 1a. By 24 months, 68 (18%) patients in the alemtuzumab group had thyroid-associated adverse events compared with 12 (6%) in the interferon beta 1a group, and three (1%) had immune thrombocytopenia compared with none in the interferon beta 1a group. Two patients in the alemtuzumab group developed thyroid papillary carcinoma. INTERPRETATION: Alemtuzumab's consistent safety profile and benefit in terms of reductions of relapse support its use for patients with previously untreated relapsing-remitting multiple sclerosis; however, benefit in terms of disability endpoints noted in previous trials was not observed here. FUNDING: Genzyme (Sanofi) and Bayer Schering Pharma.

Echocardiographic evaluation of mitral tethering for 'chordal cutting' procedure.

'Chordal cutting' is a recently proposed surgical option for the treatment of functional mitral regurgitation due to leaflet tethering. With this technique the surgeon sections second order chordae, restores leaflet's convexity towards the left atrium and eliminates mitral incompetence. Preoperative assessment of tethering mechanism, degree of leaflet distortion, surface of coaptation, annular dilation, origin and quantification of valve incompetence by echocardiographic means is essential in indicating this surgical option. Intraoperative transesophageal evaluation is crucial to assess the morphology and the absence or degree of residual incompetence after procedure.

Echocardiographic images in mitral valve repair by "edge to edge" technique.

The "edge to edge" or "double orifice" technique is a new surgical option of mitral repair when functional valve insufficiency is present, due to ischemic or dilated cardiomyopathy. This technique is not frequently used and radically changes mitral anatomy and hemodynamic. Therefore, echocardiographic examination is completely different and implies good experience to evaluate postoperative valve function. For these reasons we present a case report of a patient who underwent this repair and was evaluated in the follow up by standard transthoracic echocardiography: the anatomical and functional assessment that was satisfactory compared with transesophageal examination is documented.

Septal dissection and rupture evolved as an inferobasal pseudoaneurysm.

We report two cases of postinfarction dissecting hematoma of the interventricular septum with restrictive ventricular septal defect that evolved as an inferobasal pseudoaneurysm. The difficult anatomical pattern was assessed by two-dimensional (2-D) echocardiography with Doppler and color analysis, left ventriculography and perioperative transoesophageal echo. Because the patient had no signs of heart failure, the surgical repair was successfully delayed until the dissecting tissue became fibrotic. Problems of diagnosis, decision making and surgical management are discussed.

Hardware of the flight experiment "Quail-SK" transport incubator.

The transportation of quail eggs in various stages of incubation was used in an experiment at the orbital station MIR by the Slovak astronaut, Bella in February 1999. Device description, diagrams, and experimental results are presented in this paper.

Results with the Novacor assist system and evaluation of long-term assistance.

OBJECTIVE: The great number of patients awaiting heart transplant and the shortage of donors has led to the increasing use of left ventricular assist devices (LVAD) for those patients that cannot wait only on medical therapy. In this study we analyze our experience in order to evaluate the possibility of long-term assistance. METHODS: We have implanted LVAD Novacor in 36 patients with a mean age of 50.4 years. They were all critical candidates for transplant on high doses of inotrops. We evaluated the clinical and hemodynamic results and studied statistically the relative risk of complications at different time intervals of support. RESULTS: In all cases we had a statistically significant improvement of: cardiac output, wedge pressure, pulmonary vascular resistance and mean pulmonary pressure. Eleven patients died on the device, 23 underwent heart transplant and two are still on the device. Causes of death were mostly related to cerebrovascular events or multiorgan failure. Seven of the 23 patients who underwent heart transplant died with a survival rate after transplant of 69.5% and an overall survival rate of 50%. Complications occurred in 33 patients with: 24 strokes, eight TIAs, four cerebral hemorrhages, three peripheral embolisms, seven cable infections, two pocket infections, two sepsis, two major lung infections, one mediastinitis, one right ventricular failure and three multiorgan failure. Time-related analysis showed that these complications occurred mostly during the first 3 months of assistance and this is particularly true for cerebrovascular events. The incidence of infections remained constant during the follow-up period. With a mean time of assistance of 203.1 days we had only two cases of device malfunction at 662 and 1297 days. CONCLUSIONS: LVAD Novacor has provided reliable mechanical performance and good hemodynamic improvement. Most complications seem to occur in the first 90 days, therefore long-term assistance could be considered. A reduction of the high rate of thromboembolic complications remains mandatory to improve the clinical results.

Left ventricular mass reduction after aortic valve replacement: homografts, stentless and stented valves.

BACKGROUND: We studied the effect of four different types of prosthetic aortic valves on time course and extent of regression of left ventricular hypertrophy after aortic valve replacement for aortic stenosis. METHODS: Four groups of 10 patients each were randomly assigned to receive: (1) aortic homograft preserved in antibiotic solution at 4 degrees C, (2) Toronto stentless porcine valve, (3) Medtronic Freestyle stentless valve, or (4) Medtronic Intact aortic valve. The left ventricular mass index, effective orifice area index, and peak and mean transaortic gradients were measured by Doppler echocardiography before the operation and 8 months postoperatively. RESULTS: The hemodynamic performance indices were much better for the homograft and stentless valves than for the stented one. The absolute left ventricular mass index reduction was greater in the homograft group compared with the Intact (p = 0.0004) and Toronto (p = 0.007) groups. The extent of percent left ventricular mass index reduction was greater only in the homograft group versus Intact group (p = 0.005). The multilinear regression analysis showed that the only predictors of a larger percentage of left ventricular mass index reduction were the homograft type, a higher valve size index, and a higher preoperative left ventricular mass index. CONCLUSIONS: When a stentless or homograft aortic valve was used instead of a stented valve to replace a stenotic aortic valve there was more complete or at least faster regression of left ventricular hypertrophy. The hemodynamic performance of stentless porcine valves was similar to that of aortic homografts, nevertheless the aortic homografts preserved in antibiotic solution offered a faster regression of left ventricular hypertrophy during the same period of time.

Neuromuscular disorders and acute respiratory failure.

This article discusses the assessment and management of rapidly progressive weakness due to neuromuscular disorders. The authors review elements helpful in determining the causes of weakness including pertinent history and laboratory studies. Disorders are classified according to the level of the motor unit involved and triage/management decisions are described. In addition, respiratory function assessment is reviewed. The latter part of this article is devoted to evaluation and management of two of the most common disorders, Guillain-Barré syndrome and myasthenia gravis.

Surgical management of aortopulmonary window.

BACKGROUND: Aortopulmonary window is a rare anomaly, and a variety of surgical techniques have been described for its closure. METHODS: We treated 6 infants with aortopulmonary window between 1993 and 1995. Three had associated type A interrupted aortic arch, and another had a muscular ventricular septal defect. The diagnosis was made by echocardiography, confirmed by cardiac catheterization in 4 infants. In 1 very sick neonate with interrupted arch, diagnosis of the window was considerably delayed. In 4 patients, we closed the window by using a flap of pulmonary artery, which was reconstructed without using a patch. In 2 neonates with interrupted arch we anastomosed the mobilized descending aorta directly to the aortic defect of the aortopulmonary window, closing the pulmonary artery with a pericardial patch. RESULTS: There were no hospital deaths, and all patients are in New York Heart Association functional class I at a mean follow-up of 30 months. Echocardiography shows no significant distortion of the great vessels. CONCLUSIONS: The techniques described achieve excellent results using only autologous tissues with the potential for normal growth.

Cognitive dysfunction as the major presenting feature of Becker's muscular dystrophy.

We report four patients, currently aged 15, 17, 19, and 42 years, with X-linked dystrophinopathy who presented with mental retardation (IQ range, 60-68) and psychiatric disturbance in the absence of muscle weakness. All patients had elevated serum creatine kinase and dystrophic changes on muscle biopsy. There were alterations in the size and abundance of dystrophin on immunohistochemistry and immunoblotting in all cases, consistent with a molecular diagnosis of Becker's muscular dystrophy. Two patients had deletions of the dystrophin gene on DNA analysis. These findings suggest that Becker's muscular dystrophy may be associated with a predominantly neuropsychiatric presentation and that dystrophinopathy should be considered in the differential diagnosis of unexplained cognitive or psychiatric disturbance in males. Serum creatine kinase may provide an adequate screening test in this clinical situation.

[Doppler echocardiographic analysis of the short-term results of surgical repair of mitral valve prolapse in myxomatous degeneration]. / Valutazione ecocardiografica Doppler dei risultati a breve termine dell'intervento di riparazione di prolasso valvolare mitralico nella degenerazione mixomatosa.

Ten consecutive patients with pure mitral regurgitation due to floppy valve underwent valve repair operations. Postoperative mitral continence or regurgitation and diastolic flow across the valve were evaluated by Doppler echocardiography. Mean follow-up was 6.4 months. Four patients showed minimal and 3 mild regurgitation; no regurgitation was detected in 3. A significant peak diastolic atrioventricular gradient (10 mmHg) was observed in only one patient. All patients showed symptomatic improvement and a decrease in ventricular diameters. Repair of floppy mitral valves is feasible and gives good results. Doppler echocardiography is a useful technique for monitoring postoperative valve function.

Comparison of steady-state blood levels of two carbamazepine formulations.

The steady-state plasma level produced by brand-name carbamazepine (CBZ) (Tegretol, Ciba-Geigy) was compared with a generic formulation (Parke-Davis) in 10 subjects with partial epilepsy in a randomized, double-blind, cross-over clinical trial. In addition, seizure frequency and clinical and laboratory signs of toxicity were evaluated. Our results failed to show any difference in CBZ blood levels, seizure frequency, or clinical or laboratory signs of toxicity in patients receiving either the brand-name or generic formulation.

[Acute dissection of the thoracic aorta. Proposal of a new surgical technic]. / La dissezione acuta dell'aorta toracica. Proposta di una nuova tecnica chirurgica.

Acute aortic dissection is a challenging surgical disease. Replacement of the supracoronary aorta alone can be followed by recurrent aneurysm formation at the level of the residual aortic root. The Bentall procedure prevents this late complication but intraoperative haemorrhage may be severe and valve replacement is always mandatory. A new surgical technique is presented which has been adopted in seven consecutive patients with no deaths. With this procedure, strengthening of the aortic root is obtained by inserting three Dacron Double Velour patches "between" the internal and external aortic lamina, one for each sinus of Valsalva. The patches override the coronary ostia which are left wide patent, and are anchored directly to the aortic anulus by single mattress sutures which reduce the size of the anulus. Suspension of the valve leaflets to the patches overriding each other at the commissures together with anuloplasty reestablish valve continency. The two aortic stumps are secured with running sutures over the free edge and a tubular Dacron graft is then anastomosed to them. The procedure reinforces the aortic root, will prevent recurrent aneurysm formation and avoids at the same time valve replacement, when unnecessary, and coronary arteries reimplantation.