Patient-reported, clinical and radiological factors associated with the result after non-surgical management of acute AC joint dislocation Rockwood type III and V.

PURPOSE: The treatment of Rockwood type III and V acromioclavicular (AC) joint dislocations is controversial, and an individualized treatment algorithm is yet to be developed. The objective of this study was to investigate the association of demographical, clinical, patient-reported and radiological variables with the Western Ontario Shoulder Instability Index (WOSI) score and risk of surgery. METHODS: Inclusion criteria for this prospective cohort study were patients aged 18-60 with an acute AC joint dislocation with >25% increase in the coracoclavicular distance on bilateral Zanca radiographs. Patients were treated non-surgically with 3 months of home-based training and the option of delayed surgical intervention. The outcomes were the WOSI score and surgery yes/no. Demographical, clinical, patient-reported (WOSI and Shoulder Pain and Disability Index [SPADI]) and radiological variables were collected at baseline and 6 weeks after the injury and investigated for association with the outcomes at 3 months, 6 months and 1 year. RESULTS: Ninety-five patients with Rockwood type III/V AC joint dislocation were included. Pre-injury participation in overhead/collision sports was a risk factor for surgery with an odds ratio of 5 (p = 0.03). Reduced range of motion (ROM) at baseline was associated with reduced WOSI scores and increased risk of surgery. At 6 weeks, reduced ROM, increased SPADI and increased pain during cross-over were associated with the outcomes. Radiological measurements were not correlated with the result. At the 6 weeks follow-up, patients eventually requiring surgery could be detected with a sensitivity of 100% and a specificity of 94% based on a SPADI score of >30 and a ROM ≤ 140° in shoulder flexion or abduction. CONCLUSION: ROM was the only variable consistently associated with both WOSI and risk of surgery. Six weeks after the injury, it was possible to detect patients in need of surgery based on ROM and SPADI with a sensitivity of 100% and a specificity of 94%. LEVEL OF EVIDENCE: Level II.

The ISAKOS subclassification of Rockwood type III AC joint dislocations in a stable type A and an unstable type B is not clinically relevant.

PURPOSE: The treatment of Rockwood type III AC joint dislocations has been debated for decades. In 2014, the International Society of Arthroscopy, Knee Surgery and Orthopaedic Sports Medicine (ISAKOS) Upper Extremity Committee suggested a subclassification of the injury into type A, considered stable and best treated nonsurgically, and type B, considered unstable and best treated surgically. Type B is defined by the presence of scapular dyskinesis and overriding of the clavicle to the acromion on a modified lateral radiograph. The objective of the study was to investigate if this subclassification is clinically relevant. METHODS: This was a prospective cohort study. Inclusion criteria were patients aged 18-60 years with acute AC joint dislocation and a baseline Zanca radiograph with an increase in the CC distance of >25% compared to the uninjured side. All patients were treated nonsurgically with 3 months of home-based training and with the option of delayed surgical intervention. Patients were assessed at baseline and at follow-ups 6 weeks, 3 months, 6 months and 1 year after the injury. At the 6-week follow-up, patients were graded as stable and unstable according to the ISAKOS criteria. Outcomes were the Western Ontario Shoulder Instability Index (WOSI) and referral for surgery. RESULTS: At 6 weeks of follow-up, 20 patients were classified as stable type A and 69 were classified as unstable type B. The ISAKOS subclassification was not clinically relevant, but patients graded as stable had statistically significantly better WOSI scores at 6 months compared to the unstable group (p = 0.03) but not at 3 months or 1 year. Nine patients (9.5%), all from the unstable group, were referred for surgery. No patients from the stable group underwent surgery (n.s). CONCLUSION: The ISAKOS subclassification of Rockwood type III in a stable type A and an unstable type B is not clinically applicable. LEVEL OF EVIDENCE: Level II.

Precision Medicine Approach for Cardiometabolic Risk Factors in Therapeutic Apheresis.

Lipoprotein apheresis (LA) is currently the most powerful intervention possible to reach a maximal reduction of lipids in patients with familial hypercholesterolemia and lipoprotein(a) hyperlipidemia. Although LA is an invasive method, it has few side effects and the best results in preventing further major cardiovascular events. It has been suggested that the highly significant reduction of cardiovascular complications in patients with severe lipid disorders achieved by LA is mediated not only by the potent reduction of lipid levels but also by the removal of other proinflammatory and proatherogenic factors. Here we performed a comprehensive proteomic analysis of patients on LA treatment using intra-individually a set of differently sized apheresis filters with the INUSpheresis system. This study revealed that proteomic analysis correlates well with routine clinical chemistry in these patients. The method is eminently suited to discover new biomarkers and risk factors for cardiovascular disease in these patients. Different filters achieve reduction and removal of proatherogenic proteins in different quantities. This includes not only apolipoproteins, C-reactive protein, fibrinogen, and plasminogen but also proteins like complement factor B (CFAB), protein AMBP, afamin, and the low affinity immunoglobulin gamma Fc region receptor III-A (FcγRIIIa) among others that have been described as atherosclerosis and metabolic vascular diseases promoting factors. We therefore conclude that future trials should be designed to develop an individualized therapy approach for patients on LA based on their metabolic and vascular risk profile. Furthermore, the power of such cascade filter treatment protocols may improve the prevention of cardiometabolic disease and its complications.

Defining advanced practice in radiation therapy: A feasibility assessment of a new healthcare provider role in Ontario, Canada.

INTRODUCTION: This study assesses the feasibility of a new role for radiation therapists in Ontario, Canada, called the Advanced Practice Radiation Therapist (APRT), which would address health service pressures and improve patients' access to care. METHODS: A literature search and expert consensus were used to define advanced practice. A standardized template was used to record each APRTs activities/competencies, along with the requisite knowledge, skills and judgment required to perform these competencies. A thematic analysis of the lists was undertaken to develop a single competency profile. Seven APRTs were deployed at four cancer centres to gather contextual information on the development and integration of the new role. RESULTS: The definition of AP consists of seven key traits and includes a framework identifying stages of practice from entry-level practitioner through expert to advanced practitioner. The competency profile consists of clinical, technical and professional domains which further define the scope of practice and shepherd the role through stages of implementation. Role testing showed support for the role and demonstrated that APRTs can deliver specialized services, perform delegated tasks and their work can lead to program efficiencies and new services. The new role may also lead to improved radiation therapist recruitment rates and work satisfaction. CONCLUSIONS: This feasibility assessment served as the foundation for the future long-term implementation of the Clinical Specialist Radiation Therapist (CSRT) Project. As of 2018, there were 24 CSRTs in Ontario. The APRT role is a natural progression for a readying profession which can play a transformative role in addressing health human resource shortages.

Effect of high pressure treatment on the color of fresh and processed meats: A review.

High pressure (HP) treatment often results in discoloration of beef, lamb, pork, and poultry. The degree of color changes depends on the physical and chemical state of the meat, especially myoglobin, and the atmospheric conditions during and after pressurization. A decreased redness is attributed to a large degree to the oxidation of the bright red oxymyoglobin or the purplish deoxymyoglobin into the brownish metmyoglobin, as well as to the denaturation of myoglobin. Surely, the high myoglobin content makes beef more exposed to this discoloration compared to the white chicken meat. In addition, HP treatment causes denaturation of myofibrillar proteins followed by aggregation, consequently, changing the surface reflectance and increasing lightness. Other intrinsic and extrinsic factors may affect the pressure-induced color changes positively or negatively. In this review, the pressure-induced color changes in meat are discussed in relation to modification of the myoglobin molecule, changes in the meat microstructure, and the impact of the presence of different chemical compounds and physical conditions during processing.

Arthroscopic management of suprascapular neuropathy of the shoulder improves pain and functional outcomes with minimal complication rates.

PURPOSE: The purpose of this study was to systematically assess the arthroscopic management of suprascapular neuropathy, including the aetiology, surgical decision-making, clinical outcomes, and complications associated with the procedure. METHODS: Three databases [PubMed, Ovid (Medline), and Embase] were searched. Systematic literature screening and data abstraction was performed in duplicate to present a review of studies reporting on arthroscopic management of suprascapular neuropathy. The quality of the included studies was assessed using level of evidence and the MINORS (Methodological Index for Nonrandomized Studies) checklist. RESULTS: In total, 40 studies (17 case reports, 20 case series, 2 retrospective comparative studies, and 1 prospective comparative study) were identified, including 259 patients (261 shoulders) treated arthroscopically for suprascapular neuropathy. The most common aetiology of suprascapular neuropathy was suprascapular nerve compression by a cyst at the spinoglenoid notch (42%), and the decision to pursue arthroscopic surgery was most commonly based on the results of clinical findings and investigations (47%). Overall, 97% of patients reported significant improvement in or complete resolution of their pre-operative symptoms (including pain, strength, and subjective function of the shoulder) over a mean follow-up period of 23.7 months. Further, there was a low overall complication rate (4%) associated with the arthroscopic procedures. CONCLUSION: While most studies evaluating arthroscopic management of suprascapular neuropathy are uncontrolled studies with lower levels of evidence, results indicate that such management provides patients with significant improvements in pain, strength, and subjective function of the shoulder, and has a low incidence of complications. Patients managed arthroscopically for suprascapular neuropathy may expect significant improvements in pain, strength, and subjective function of the shoulder. LEVEL OF EVIDENCE: Level IV, systematic review of level II to IV studies.

Best Practice Recommendations for the Retention of Radiotherapy Records.

This paper offers best practice recommendations for the maintenance and retention of radiotherapy health records and technical information for cancer programmes. The recommendations are based on a review of the published and grey literature, feedback from key informants from seven countries and expert consensus. Ideally, complete health records should be retained for 5 years beyond the patient's lifetime, regardless of where they are created and maintained. Technical information constituting the radiotherapy plan should also be retained beyond the patient's lifetime for 5 years, including the primary images, contours of delineated targets and critical organs, dose distributions and other radiotherapy plan objects. There have been increased data storage and access requirements to support modern image-guided radiotherapy. Therefore, the proposed recommendations represent an ideal state of radiotherapy record retention to facilitate ongoing safe and effective care for patients as well as meaningful and informed retrospective research and policy development.

Influence of systemic bone mineral density on atlantoaxial subluxation in patients with rheumatoid arthritis.

Osteopenia and osteoporosis were independent predictive factors for higher atlantoaxial subluxation occurrence in patients with lower body mass index. Our findings suggest that patients with rheumatoid arthritis with osteopenia or osteoporosis, particularly those with lower body mass index (BMI), should be screened regularly to determine the status of their cervical spines. INTRODUCTION: Cervical spine involvement in rheumatoid arthritis (RA) patients may cause serious adverse effects on quality of life and overall health. This study aimed to evaluate the association between atlantodental interval (ADI), atlantoaxial subluxation (AAS), and systemic bone mineral density (BMD) based on BMI variations among established patients with RA. METHODS: The ADI was transformed to the natural log scale to normalize distributions for all analyses. Multivariable linear regression analyses were used to identify independent predictive factors for ADI based on each BMD classification. Multivariate Cox regression analyses were also performed to identify independent predictive factors for the risk of AAS, which were classified by tertile groups of BMI. RESULTS: A total of 1220 patients with RA who had undergone at least one or more cervical radiography and BMD assessments were identified and enrolled. We found that the association between BMD and ADI (ß, -0.029; 95% CI, -0.059 to 0.002; p = 0.070) fell short of achieving statistical significance. However, the ADI showed a 3.6% decrease per 1 BMI increase in the osteoporosis group (ß, -0.036; 95% CI, -0.061 to -0.011; p = 0.004). The osteopenia and osteoporosis groups showed about a 1.5-fold and a 1.8-fold increased risk of AAS occurrence among the first tertile of the BMI group. CONCLUSIONS: Our study showed a possible association between lower BMD and AAS occurrence in patients with RA with lower BMI. Further studies are needed to confirm our findings.

Effective treatment of different phenotypes of chronic urticaria with omalizumab: Case reports and review of literature.

Despite the excellent efficacy and safety profile of omalizumab in chronic spontaneous urticaria (CSU), there are scarce data concerning its role in the treatment of refractory cases with different phenotypes of urticaria. We describe our experience with the therapy of nine patients with CSU co-existing with delayed pressure urticaria (DPU) or angioedema or both and refractory to treatment with high-dose antihistamines. The first patient, with severe CSU and recurrent angioedema, did not respond well to cyclosporine A or corticosteroids and suffered from numerous side effects of long-term corticosteroid therapy. The second patient presented with severe symptoms of DPU, which first of all prevented any daily activities of the professional routines. Both patients showed a complete remission of urticaria after the first injection of omalizumab. The third patient with CSU and severe DPU had been ineffectively treated for more than 20 years with various medications. Following the administration of omalizumab, the symptoms of CSU subsided but those of DPU intensified, and the drug was withdrawn after two cycles. In another four patients with refractory CSU and angioedema, the symptoms subsided after the first administration of omalizumab, and the patients have been in remission for about 5 weeks. In the remaining two patients, the symptoms did not resolve despite four 300 mg doses of omalizumab. It is important to establish a therapeutic regimen with omalizumab (150-300 mg; every 4-8 weeks) tailored to individual patient's needs and dependent on the type of urticaria; this may minimize unnecessary the medication exposure, adverse drug effects, and healthcare costs.

Sarcoidosis and tuberculosis: a connection to the human leukocyte antigen system.

Infectious, genetic factors, and autoimmunity have been considered as potential causes of sarcoidosis (SA). Pathological similarities between SA and tuberculosis (TB) suggest M. tuberculosis antigen(s) as causative agent(s). Our published comparative analysis of the human leukocyte antigens (HLA) system in patients with SA or TB in the same ethnic group revealed that some antigens were connected with high risk of developing of SA or TB, but other were comparable in both patient populations. Is it possible that the predominating occurrence of HLA antigens characteristic for TB may cause tuberculosis in patients with SA? To answer this question we evaluated the HLA class I and II alleles frequency by PCR amplification with sequence-specific primers in three women with histopathologically proven pulmonary SA, who developed bacteriologically confirmed TB on a corticosteroids (CS) therapy. Analysis of HLA in every case separately revealed a trend for higher occurrence of both alleles predisposing and protecting from TB than SA, in comparison with healthy individuals in our previously mentioned HLA genotyping study. Overall, the number of alleles predisposing to TB was statistically greater than the number of alleles connected with a high risk of developing SA. Also, the frequency of protecting alleles was statistically higher for TB than for SA. Therefore, SA in these patients developed at first, and the presence of additional environmental factors, e.g., age, CS might decrease an immune response and provoked TB. There is a possibility that the occurrence of HLA antigen more associated with high risk of developing TB than SA causes the development of tuberculosis in our patients with sarcoidosis.

Delivery of brachytherapy for cervical cancer: organisational and technical advice to facilitate high-quality care.

AIMS: Brachytherapy is a standard therapy for cervical cancer; it allows for the delivery of a high dose of radiation to the tumour while sparing the surrounding healthy tissues. With this document, the Brachytherapy Cervical Cancer Expert Working Group (BCCEWG) aimed to provide advice on organisational and technical aspects of the delivery of brachytherapy services in Ontario, Canada. MATERIALS AND METHODS: We sought technical documents, practice guidelines and standards through an environmental scan of internet resources, an iterative search of the literature on MEDLINE and EMBASE, and a search of reference lists of included documents. RESULTS: We identified 20 guidance documents authored by 10 organisations; 11 documents were identified through the environmental scan, five through the literature search and four from reference lists. The recommendations included in this document were developed by the BCCEWG through the selection and review of the evidence and informal consensus. CONCLUSIONS: These organisational recommendations aim to set the stage for high-quality delivery of brachytherapy for cervical cancer services in the province of Ontario, Canada. They address the characteristics of the practice setting, including facilities, equipment, delivery suite, imaging technologies, treatment planning and dosimetry; the practice team, including team members, roles, training, team caseload/volumes and qualifications; and the quality assurance domain, including documentation, audit, safety and quality control.

Organisational standards for the delivery of intensity-modulated radiation therapy in Ontario.

By minimising the effect of irradiation on surrounding tissue, intensity-modulated radiation therapy (IMRT) can deliver higher, more effective doses to the targeted tumour site, minimising treatment-related morbidity and possibly improving cancer control and cure. A multidisciplinary IMRT Expert Panel was convened to develop the organisational standards for the delivery of IMRT. The systematic literature search used MEDLINE, EMBASE, the Cochrane Database, the National Guidelines Clearing House and the Health Technology Assessment Database. An environmental scan of unpublished literature used the Google search engine to review the websites of key organisations, cancer agencies/centres and vendor sites in Canada, the USA, Australia and Europe. In total, 22 relevant guidance documents were identified; 12 from the published literature and 10 from the environmental scan. Professional and organisational standards for the provision of IMRT were developed through the analysis of this evidence and the consensus opinion of the IMRT Expert Panel. The resulting standards address the following domains: planning of new IMRT programmes, practice setting requirements, tools, devices and equipment requirements; professional training requirements; role of personnel; and requirements for quality assurance and safety. Here the IMRT Expert Panel offers organisational and professional standards for the delivery of IMRT, with the intent of promoting innovation, improving access and enhancing patient care.

Biochemotherapy for the treatment of metastatic malignant melanoma: a clinical practice guideline.

QUESTIONS: What is the role of biochemotherapy in the treatment of metastatic malignant melanoma?What are the adverse effects and effects on quality of life of biochemotherapy as a treatment option?For the purposes of this report, "biochemotherapy" is defined as a therapeutic regimen that includes, at a minimum, chemotherapy (either single-agent or combination) and interleukin-2. PERSPECTIVES: Although early detection, appropriate surgery, and in some cases adjuvant therapy have improved outcomes, at least one third of patients with early-stage melanoma will develop metastases. Recently, in an effort to potentially maximize outcomes, the combination of chemotherapy and immunotherapy (biochemotherapy) was evaluated. The level of interest that this approach has generated, particularly with regard to the apparently high response rates seen in this otherwise devastating illness, was sufficient to merit closer examination by the Melanoma Disease Site Group (dsg) of Cancer Care Ontario's Program in Evidence-based Care (pebc). OUTCOMES: Outcomes of interest include response rate, diseasefree survival, overall survival, quality of life, and incidence of grades 3 and 4 toxicities. METHODOLOGY: Evidence was selected and reviewed by three members of the pebc's Melanoma dsg and by two methodologists. The present practice guideline report was reviewed and approved by the Melanoma dsg, which comprises medical and radiation oncologists, surgeons, and dermatologists. External review by Ontario practitioners was obtained through a mailed survey, the results of which were incorporated into the practice guideline. Final approval of the original guideline report was obtained from the pebc's Report Approval Panel. RESULTS: Clinical recommendations were drafted based on the evidence identified through a systematic review. The practice guideline report with draft recommendations was mailed to Ontario practitioners for external review and to the Report Approval Panel. Feedback from both groups was incorporated into this report to create the final practice guideline. PRACTICE GUIDELINE: The recommendations that follow apply to adult patients with metastatic malignant melanoma. Because of the inconsistent results of the available studies with regard to benefit (response, time to progression, and survival) and consistently high toxicity rates, biochemotherapy is not recommended for the treatment of metastatic melanoma.

Single-agent interleukin-2 in the treatment of metastatic melanoma.

QUESTIONS: What is the role of single-agent interleukin-2 (il-2) in the treatment of adults with metastatic melanoma? If there is a role for single-agent il-2, what patient population can appropriately be considered for treatment? If there is a role for single-agent il-2, what dose and schedule are appropriate? What are the toxicities associated with il-2? PERSPECTIVES: Many agents have been investigated for antitumour activity in melanoma, but few have shown promising response rates. Early detection, appropriate surgery, and adjuvant therapy have all improved outcomes, but approximately one third of patients with early-stage disease will nevertheless develop metastases. Single-agent il-2 has attracted much attention over the past several years. A number of randomized trials and many phase ii trials investigating single-agent il-2 suggest that this systemic treatment produces durable responses in melanoma patients. Given the dismal survival of patients with meta-static melanoma and the limited availability of effective treatments, the Melanoma Disease Site Group (dsg) of Cancer Care Ontario's Program in Evidence-Based Care (pebc) felt that the durable responses seen with il-2 treatment warranted closer examination. OUTCOMES: Primary outcomes of interest included objective response rate, complete response rate, duration of response, toxicity, and quality of life. Secondary outcomes of interest included progression-free survival and overall survival. METHODOLOGY: A systematic review was developed, and clinical recommendations relevant to patients in Ontario were drafted. The practice guideline report was reviewed and approved by the Melanoma dsg, which comprises medical oncologists, surgeons, and dermatologists. External review by Ontario practitioners was obtained through a mailed survey, the results of which were incorporated into the practice guideline. Final review and approval of the practice guideline was obtained from the pebc's Report Approval Panel. RESULTS: The present practice guideline reflects the integration of the draft recommendations based on a systematic review of the available evidence with the feedback obtained from external review by practitioners and the Report Approval Panel. PRACTICE GUIDELINE: No studies have compared il-2 to the current standard of care-dacarbazine (dtic)-or to placebo in the treatment of metastatic melanoma. After reviewing and weighing the evidence that does exist, the opinion of the Melanoma dsg is that high-dose il-2 is a reasonable treatment option for a select group of patients with metastatic melanoma: Patients should have a good performance status (Eastern Cooperative Oncology Group 0-1) and a normal lactate dehydrogenase level.Patients should have fewer than three organs involved or have cutaneous and/or subcutaneous metastases only, and no evidence of central nervous system metastases should be present.In this select group of patients, il-2 treatment can produce durable complete remissions. High-dose il-2 is recommended to be given at 600,000 IU/kg per dose, delivered intravenously over 15 minutes, every 8 hours, for a maximum of 14 doses. High-dose il-2 delivery is recommended to be done in a tertiary-care facility by staff trained in the provision of this treatment and with appropriate monitoring. To facilitate treatment and to develop expertise in this therapeutic modality, the dsg recommends that high-dose il-2 programs be established in one or two centres in Ontario. QUALIFYING STATEMENTS: High-dose il-2 has response rates that are similar to those seen with standard chemotherapy. However, unlike chemotherapy, il-2 demonstrates low but durable complete response rates that may lead to years of benefit for patients with metastatic melanoma. Based on the available data assessing prognostic factors and patient selection, patients with non-visceral metastases and fewer metastatic sites have a much higher response rate. In these select patients, high dose il-2 may be considered for first-line therapy. The lack of large randomized trials comparing il-2 to dtic or other chemotherapy means that recommendations for this guideline are based largely on phase ii data and limited phase iii data. Further randomized data will not soon become available, because no randomized trials are currently ongoing or planned. Interleukin-2 is currently widely used in the United States, and it is an approved therapy in both Canada and the United States.

Temozolomide for the treatment of metastatic melanoma.

QUESTIONS: What is the role of single-agent temozolomide in the treatment of patients with metastatic melanoma? In comparison with single-agent temozolomide, does the addition of interferon-alpha to temozolomide improve disease-free survival, overall survival, or response rates? In comparison with single-agent temozolomide, does the addition of thalidomide to temozolomide improve disease-free survival, overall survival, or response rates? PERSPECTIVES: Because of its oral route of administration and its ability to cross the blood-brain barrier, temozolomide is a potentially attractive chemotherapy agent for adult patients with unresectable metastatic malignant melanoma. To provide treatment recommendations for this new agent, the Melanoma Disease Site Group (dsg) of Cancer Care Ontario's Program in Evidence-Based Care (pebc) decided to review the available literature on single-agent temozolomide and on temozolomide in combination with interferon-alpha or thalidomide. OUTCOMES: Outcomes of interest included response rates, disease-free survival, overall survival, quality of life, and adverse effects. METHODOLOGY: Evidence was selected and reviewed by two members of the Melanoma dsg and by methodologists. The present practice guideline report was reviewed and approved by the Melanoma dsg, which comprises medical and radiation oncologists, surgeons, and dermatologists. External review was obtained through a mailed survey of Ontario practitioners, the results of which were reflected in revisions to the practice guideline. Final approval of the guideline report was obtained from the Report Approval Panel of the pbec. PRACTICE GUIDELINE: These recommendations apply to adult patients with unresectable metastatic malignant melanoma. It is reasonable to use temozolomide at a dose of 200 mg/m(2) orally for 5 days every 4 weeks as initial systemic treatment for patients with unresectable metastatic malignant melanoma. The addition of moderate-dose interferon-alpha 2b has produced a significantly higher response rate than has single-agent temozolomide in a large randomized phase iii study. However, overall survival was not altered, and grades 3 and 4 hematologic toxicities were higher with the combined treatment. At the present time, the addition of interferon-alpha to temozolomide is not recommended. One randomized phase ii study and six other phase ii studies showed encouraging response rates when thalidomide was combined with temozolomide. However, the doses and schedules of temozolomide in those studies differed from the conventionally prescribed doses and schedules. It is not clear whether the improved response rates were attributable to the small number of patients in the studies, the different temozolomide doses and schedules, or the addition of thalidomide. Further phase iii studies are required to confirm whether a benefit is associated with the combination of temozolomide and thalidomide. Therefore, at this time, it is not recommended that thalidomide be combined with temozolomide. QUALIFYING STATEMENTS: Dacarbazine is the only chemotherapy drug currently approved for the treatment of metastatic malignant melanoma. In large randomized trials, response rates with dacarbazine ranged from 6% to 15%. Almost all responses were partial, with a median response duration of only 7-8 months. Given these disappointing overall results, the consensus among most physicians who are treating patients with metastatic malignant melanoma is that recommending more convenient treatment or experimental treatment to these patients is appropriate. Because of oral dosing, temozolomide is a reasonable choice, particularly for patients who would have difficulty traveling to cancer centres for intravenous chemotherapy. Temozolomide has demonstrated efficacy equal to that of dacarbazine in a randomized phase iii trial. However, unlike dacarbazine, temozolomide is a convenient oral treatment that penetrates the blood-brain barrier and that has shown activity against brain metastases. Although surgery is the preferred treatment modality for patients with solitary brain metastases from melanoma, temozolomide is the preferred chemotherapy for patients with brain metastases who require systemic treatment.

Swimmers' painful shoulder arthroscopic findings and return rate to sports.

Shoulder pain is the most common musculo-skeletal complaint in competitive swimmers. It remains one of the shoulder pain syndromes in overhead athletes where no golden standard of treatment exists. Eighteen competitive swimmers who all had undergone shoulder arthroscopy for therapy-resistant shoulder pain were retrospectively evaluated with respect to operative findings and ability to return to their sport after the operation. The most common finding at arthroscopy was labral pathology in 11 (61%) and subacromial impingement in five shoulders (28%). Operative procedures included debridement in 11 swimmers, partial release of the coraco-acromial ligament in four, and bursectomy in four. Sixteen (89%) responded to the follow-up evaluation. Nine swimmers (56%) were able to compete at preinjury level after 4 (2-9) months. Findings at arthroscopy suggest that the term "Swimmer's shoulder" covers a variety of pathologies including labral wearing and subacromial impingement. Arthroscopic debridement of labral tears or bursectomy in swimmers with shoulder pain has a low success rate with regard to return to sport. Further understanding and investigation of this syndromes complex pathophysiology is needed.

Usefulness of silicone plate for sellar floor reconstruction.

During the transsphenoidal approach (TSA), the proper sellar floor reconstruction plays an important role in the surgical results. The authors have evaluated the usefulness of a silicone as a substitute for bone splint in sellar floor reconstruction. Silicone plates were used in 10 patients who had 7 pituitary adenomas, 2 Rathke's cleft cysts, and 1 metastatic tumor. Among the ten cases, seven underwent standard TSAs and three received extended TSAs. The silicone plate was cut to a size slightly larger than that of bone window, inserted with a three-pronged fork, and then adjusted precisely. In nine patients, complications that related to surgical repair did not occur. A postoperative cerebrospinal fluid (CSF) rhinorrhea occurred in one pituitary macroadenoma, and no infection was observed in any case. From the authors' experience, advantages of the silicone plate are its simplicity to shape for any size of defects, and the easy detectability of the previous bone window at reoperation.

Differential evolution and stability of epitope-specific CD8(+) T cell responses in EBV infection.

Murine models of lymphocytic choriomeningitis virus infection suggest that the memory CD8(+) T cell repertoire is reflective of the CD8(+) T cell repertoire generated during acute infection. Less is known regarding the evolution of CD8(+) T cell repertoires during human viral infections. We therefore examined epitope-specific CD8(+) T cell responses in a large cohort of individuals with acute through latent Epstein-Barr virus infection. Using 16 of 20 published EBV epitopes restricted by HLA-A2, HLA-A3 or HLA-B7, we showed that lytic cycle-specific CD8(+) T cell responses predominated during acute EBV infection. However, whereas HLA-A2(+)-restricted BMLF-1-specific CD8(+) T cell responses were maintained through latency, HLA-A2(+)- and HLA-B7(+)-restricted BZLF-1, as well as HLA-A3(+)-restricted BRLF-1 CD8(+) T cell responses, were generated but not readily maintained. Analyses of CD8(+) T cell responses to EBV latent cycle Ags showed delayed detection and lower frequencies of latent epitope-specific CD8(+) T cell responses during acute EBV infection, with maintenance of these responses 1 yr post-EBV infection. Early BMLF-1 and EBNA-3A epitope-specific CD8(+) T cell frequencies did not correlate with their frequencies at 1 yr postinfection. Interestingly, populations of EBV-specific CD8(+) T cells were stable during 20 mo in our long term EBV-seropositive populations, suggesting homeostasis between virus and the host immune system. This study demonstrates that CD8(+) T cell repertoires generated during persistent viral infections are not simply reflective of the initial pool of CD8(+) T cells and provides evidence that the generation of CD8(+) T cell responses to a persistent infection is a dynamic process.