AIMS AND OBJECTIVES:
To assess the profile, evaluation criteria and fatigue treatment.
Fatigue, characterised by tiredness, weakness or lack of energy, involves physical, cognitive and emotional aspects. Its aetiology is not well defined and the prevalence ranges from 30-70% in women with breast cancer, reaching up to 80% when they are undergoing radiotherapy. This is one of the most frequent side effects of radiotherapy, and it may interfere with self-esteem, social activities and quality of life.
Literature systematic review.
A search for studies published from 2000-2010 was carried out in Pubmed, Scielo and Bireme databases, using the descriptors fatigue and radiotherapy and their correlates in Portuguese.
We selected 12 articles of 1085 found. The number of studies involving breast cancer was higher than those related to gynaecological cancer. Functional Assessment of Cancer Therapy-Fatigue was the most used scale specifically for the evaluation of fatigue. Pretreatment fatigue level may be an important risk factor to aggravate it during radiotherapy and decrease the quality of life. Five studies proposed interventions, all of them involving nonpharmacological therapies: cognitive-behavioural therapy associated with hypnosis, moderate-intensity physical exercises, stretching programmes, yoga and polarity therapy. The studies showed good results in relation to fatigue, physical and psychological aspects, and quality of life.
Early detection of fatigue, using appropriate scales, is relevant to propose suitable treatments and achieve better clinical conditions, adherence and continuity of radiotherapy treatment, aiming to ensure more effective responses.
RELEVANCE TO CLINICAL PRACTICE:
Fatigue is a frequent symptom in patients undergoing radiotherapy. It may become a factor that limits or prevents the continuity of radiotherapy and therefore should be diagnosed in the initial appointments, so that it can be properly treated.
Bisphosphonates prevent skeletal-related events in patients with metastatic breast cancer. Their effect in early breast cancer is controversial. Ibandronate is an orally and intravenously available amino-bisphosphonate with a favorable toxicity profile. It therefore qualifies as potential agent for adjuvant use.
PATIENTS AND METHODS:
The GAIN (German Adjuvant Intergroup Node-Positive) study was an open-label, randomized, controlled phase III trial with a 2 × 2 factorial design. Patients with node-positive early breast cancer were randomly assigned 1:1 to two different dose-dense chemotherapy regimens and 2:1 to ibandronate 50 mg per day orally for 2 years or observation. In all, 2,640 patients and 728 events were estimated to be required to demonstrate an increase in disease-free survival (DFS) by ibandronate from 75% to 79.5% by using a two-sided α = .05 and 1-β of 80%. We report here the efficacy analysis for ibandronate, which was released by the independent data monitoring committee because the futility boundary was not crossed after 50% of the required DFS events were observed.
Between June 2004 and August 2008, 2,015 patients were randomly assigned to ibandronate and 1,008 to observation. Patients randomly assigned to ibandronate showed no superior DFS or overall survival (OS) compared with patients randomly assigned to observation (DFS: hazard ratio, 0.945; 95% CI, 0.768 to 1.161; P = .589; OS: HR, 1.040; 95% CI, 0.763 to 1.419; P = .803). DFS was numerically longer if ibandronate was used in patients younger than 40 years or older than 60 years compared with patients age 40 to 59 years (test for interaction P = .093).
Adjuvant treatment with oral ibandronate did not improve outcome of patients with high-risk early breast cancer who received dose-dense chemotherapy.
Recurrent malignant gliomas have inherent resistance to traditional chemotherapy. Novel therapies target specific molecular mechanisms involved in abnormal signaling and resistance to apoptosis. The proteasome is a key regulator of multiple cellular functions, and its inhibition in malignant astrocytic lines causes cell growth arrest and apoptotic cell death. The proteasome inhibitor bortezomib was reported to have very good in vitro activity against malignant glioma cell lines, with modest activity in animal models as well as in clinical trials as a single agent. In this paper, the authors describe the multiple effects of bortezomib in both in vitro and in vivo glioma models and offer a novel explanation for its seeming lack of activity.
Glioma stem-like cells (GSCs) were obtained from resected glioblastomas (GBMs) at surgery and expanded in culture. Stable glioma cell lines (U21 and D54) as well as temozolomide (TMZ)-resistant glioma cells derived from U251 and D54-MG were also cultured. GSCs from 2 different tumors, as well as D54 and U251 cells, were treated with bortezomib, and the effect of the drug was measured using an XTT cell viability assay. The activity of bortezomib was then determined in D54-MG and/or U251 cells using apoptosis analysis as well as caspase-3 activity and proteasome activity measurements. Human glioma xenograft models were created in nude mice by subcutaneous injection. Bevacizumab was administered via intraperitoneal injection at a dose of 5 mg/kg daily. Bortezomib was administered by intraperitoneal injection 1 hour after bevacizumab administration in doses of at a dose of 0.35 mg/kg on days 1, 4, 8, and 11 every 21 days. Tumors were measured twice weekly.
Bortezomib induced caspase-3 activation and apoptotic cell death in stable glioma cell lines and in glioma stem-like cells (GSCs) derived from malignant tumor specimens Furthermore, TMZ-resistant glioma cell lines retained susceptibility to the proteasome inhibition. The bortezomib activity was directly proportional with the cells’ baseline proteasome activity. The proteasome inhibition stimulated both hypoxia-inducible factor (HIF)–1α and vascular endothelial growth factor (VEGF) production in malignant GSCs. As such, the VEGF produced by GSCs stimulated endothelial cell growth, an effect that could be prevented by the addition of bevacizumab (VEGF antibody) to the media. Similarly, administration of bortezomib and bevacizumab to athymic mice carrying subcutaneous malignant glioma xenografts resulted in greater tumor inhibition and greater improvement in survival than administration of either drug alone. These data indicate that simultaneous proteasome inhibition and VEGF blockade offer increased benefit as a strategy for malignant glioma therapy.
The results of this study indicate that combination therapies based on bortezomib and bevacizumab might offer an increased benefit when the two agents are used in combination. These drugs have a complementary mechanism of action and therefore can be used together to treat TMZ-resistant malignant gliomas.
The authors undertook this study to document the clinical outcomes of microendoscopic laminotomy, a minimally invasive decompressive surgical technique using spinal endoscopy for lumbar decompression, in patients with lumbar spinal stenosis (LSS).
A total of 366 patients were enrolled in the study and underwent microendoscopic laminotomy between 2007 and 2010. Indications for surgery were single- or double-level LSS, persistent neurological symptoms, and failure of conservative treatment. Microendoscopy provided wide visualization through oblique lenses and allowed bilateral decompression via a unilateral approach, through partial resection of the base of the spinous process, thereby preserving the supraspinous and interspinous ligaments and contralateral musculature. Clinical symptoms and signs of low-back pain were evaluated prior to and following surgical intervention by applying the Japanese Orthopaedic Association (JOA) scoring system, Roland-Morris Disability Questionnaire (RMDQ), Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ), and 36-Item Short Form Health Survey (SF-36). These items were evaluated preoperatively and 2 years postoperatively.
Effective circumferential decompression was achieved in all patients. The 2-year follow-up evaluation was completed for 310 patients (148 men and 162 women; mean age 68.7 years). The average recovery rate based on the JOA score was 61.3%. The overall results were excellent in 34.9% of the patients, good in 34.9%, fair in 21.7%, and poor in 8.5%. The mean RMDQ score significantly improved from 11.3 to 4.8 (p < 0.001). In all categories of both JOABPEQ and SF-36, scores at 2 years’ follow-up were significantly higher than those obtained before surgery (p < 0.001). Twelve surgery-related complications were identified: dural tear (6 cases [1.9%]), wrong-level operation (1 [0.3%]), transient neuralgia (4 [1.3%]), and infection (1 [0.3%]). All patients recovered, and there were no serious postoperative complications.
Microendoscopic laminotomy is a safe and very effective minimally invasive surgical technique for the treatment of degenerative LSS.
Intraoperative radiographic localization within the cervical spine can be a challenge because of the anatomical relation of the musculoskeletal structures of the pectoral girdle. On standard cross-table lateral radiographs, these structures can produce shadowing that obscure the anatomical features of the cervical vertebrae, particularly at the caudal levels. Surgical guidelines recommend accurate intraoperative localization as a means to reduce wrong-level spine surgery, and unobstructed visualization is needed for fluoroscopy-guided placement of spinal instrumentation. In this article, the authors describe and evaluate a novel device designed to provide transient intraoperative caudal displacement of the shoulders to improve and simplify radiographic visualization of the cervical spine.
A 2-center prospective study was conducted to evaluate the device. The study included a total of 80 patients undergoing cervical spine surgery. The device was evaluated in a cohort of 50 patients undergoing elective single-level anterior discectomy and fusion and also in a second cohort of 30 patients at an independent institution. The patients in this second cohort were undergoing a variety of cervical spine procedures for multiple indications and were included in the study to allow the authors to assess the effectiveness of the device in a general neurosurgical practice. After the patients were anesthetized and positioned, consecutive standard cross-table lateral radiographs or intraoperative fluoroscopic were obtained before and after use of the device. The images were compared in order to determine the difference in lowest vertebral level visible.
There was an average difference in cervical spine visualization of +2.8 ± 0.9 vertebral levels in the first cohort, while in the second the improvement was +1.2 ± 0.7 levels (p < 0.0001 between cohorts, unpaired t-test). There was one complication, a minor shoulder abrasion, which required no specific management.
This device is safe and effective for increasing the radiographic visualization of the cervical spine for intraoperative localization.
Taking a nap, we’ve seen time and again, is like rebooting your brain. But napping may be as much of an art as it is a science. Scientists offer recommendations for planning your perfect nap, including how long to nap and when.
The sleep experts in the article say a 10-to-20-minute power nap gives you the best “bang for your buck,” but depending on what you want the nap to do for you, other durations might be ideal:
For a quick boost of alertness, experts say a 10-to-20-minute power nap is adequate for getting back to work in a pinch.
For cognitive memory processing, however, a 60-minute nap may do more good, Dr. Mednick said. Including slow-wave sleep helps with remembering facts, places and faces. The downside: some grogginess upon waking.
Finally, the 90-minute nap will likely involve a full cycle of sleep, which aids creativity and emotional and procedural memory, such as learning how to ride a bike. Waking up after REM sleep usually means a minimal amount of sleep inertia, Dr. Mednick said.
In addition to those recommendations, one surprising suggestion is to sit slightly upright during your nap, because it will help you avoid a deep sleep. And if you find yourself dreaming during your power naps, it may be a sign you’re sleep deprived. While you’re planning your nap, don’t forget to time it during the right time of day as well.