Phase I clinical study with multiple peptide vaccines in combination with tetanus toxoid and GM-CSF in advanced-stage HLA-A*0201-positive melanoma patients

Successful induction of functional tumor-specific T cells by peptide vaccination in animal models has resulted in many clinical trials to test this approach in advanced-stage melanoma patients. In this phase I clinical trial, 11 end-stage melanoma patients were vaccinated intradermally with 3 peptides: MART-1(26-35) E27L (ELAGIGILTV), tyrosinase(368-376) N375Q (YMDGTMSQV), and gp100(209-217) T210M (IMQVPFSV), admixed with tetanus toxoid and granulocyte-monocyte colony stimulating factor. The peptide vaccine was well tolerated at all tested doses, and led to grade 1-2 toxicity only. Although all patients did show a rise in antitetanus IgG titers, in only 3 patients peptide-specific CD8 T-cells were induced. In 2 cases, the response was directed against MART-1(26-35) and consisted of 0.2% and 3.3% of the CD8 population; however, in both instances these cells did not produce interferon-gamma on stimulation with the unmodified peptide. The third patient mounted a small (0.1%) response against gp100. In a fourth patient, a nonfunctional tyrosinase-specific response (0.6%) was found that was present before vaccination, but was not affected in size nor in function by the vaccine. None of the 11 patients responded clinically according to response evaluation criteria in solid tumors criteria. Although this study is a small scale phase I clinical trial, the efficacy that was observed was disappointingly low. In accordance with previously published peptide vaccination studies, these results add to the increasing evidence that peptide vaccination in itself is not potent enough as an effective melanoma immunotherapy in advanced-stage patients.     

MR imaging in screening women at increased risk for breast cancer

Hereditary breast cancer accounts for 5% to 10% of the total breast cancer burden. Screening of this group of women has been done by palpation and conventional mammography until recently, but because of the age group, mammography has a limited value. MR mammography has been demonstrated to be a reliable imaging modality in this group of patients.     

A man with atypical appendicitis

A 43-year-old man presented with acute left-sided middle and lower abdominal pain. He was diagnosed with 'left-sided acute appendicitis with non-rotation of the colon'. This is a rare and usually asymptomatic congenital anomaly.     

Disease recurrence after liver transplantation in Western Australia

BACKGROUND AND AIM: Orthotopic liver transplantation (OLT) is now the accepted therapy for end-stage chronic liver disease. Long-term survival is now expected in the majority of patients and, consequently, disease recurrence has emerged as a major concern. Our aim was to document the rate of disease recurrence after liver transplantation for conditions other than hepatitis C, in patients followed up by the Western Australian Liver Transplant Service (WALTS). METHODS: The case notes of all post-OLT patients followed up by WALTS were reviewed. Patients were excluded if survival was less than 3 months post-OLT; OLT was performed for hepatitis C alone or follow up was unavailable. Detection and definition of disease recurrence depended on pretransplant diagnosis, and were based on patient interview, biochemical, immunological and serological tests. Radiological and histological confirmation were obtained where clinically indicated. RESULTS: Eighty-seven patients were identified (89 OLTs performed). The overall rate of recurrence was 10%. Recurrence rates by disease were: primary sclerosing cholangitis (17%), primary biliary cirrhosis (12%), autoimmune hepatitis (17%), hepatitis B (40%) and alcoholic liver disease (4%). Alcohol use relapse after transplantation occurred in 25%. The overall survival post-OLT was 87%, with a mean follow up of 53 months. Survival in patients with recurrent disease was 89%. CONCLUSIONS: Disease recurrence after OLT does occur, but overall, it is relatively uncommon. Recurrence rates vary significantly and depend, in part, on indication for OLT. With medium-term follow up, recurrent disease does not have an effect on mortality.     

Range of motion in femoroacetabular impingement

Recent epidemiological studies have demonstrated that radiographic features specific to femoroacetabular impingement appear far more frequently in healthy and asymptomatic cohorts than previously anticipated. It remains unclear how incidental findings should be interpreted clinically. In addition, several authors have suggested that a decreased range of motion is part of the clinical presentation of femoroacetabular impingement. The purpose of the present study was to describe and analyze differences in range of motion between femoroacetabular impingement patients, asymptomatic individuals with incidental radiographic findings and healthy controls, using a validated electromagnetic tracking system. Furthermore, it was evaluated which motions were clinically relevant and could be used to differentiate between these three groups. We found all evaluated motions to differ significantly between patients and controls. The anterior impingement test showed a significant difference between patients and asymptomatic cases. In conclusion, functional evaluation of the range of motion appeared in this study as a useful tool in the diagnostic work-up of femoracetabular impingement.     

Evaluation of implementation of the ParkFit program: A multifaceted intervention aimed to promote physical activity in patients with Parkinson's disease

Objectives

We recently completed the ParkFit study, a two-year randomized controlled trial including 586 sedentary Parkinson's disease (PD) patients, that evaluated a multifaceted intervention (ParkFit program) to promote physical activity. The results showed that the ParkFit program enables PD patients to become physically more active, suggesting that this intervention should now be further implemented into clinical practice. To facilitate this process, we here evaluate the implementation of the ParkFit program.

Methods

The ParkFit program was evaluated in three ways: (a) experiences of patients and physiotherapists, as investigated using interviews and questionnaires; (b) factors associated with changed activity levels; and (c) subgroup analyses to identify differential effects in subgroups of patients based on baseline physical activity level, age, gender, disease severity, disease duration, and mobility.

Results

The ParkFit program was well received: 73% of patients indicated they would recommend the program to other patients, and 90% of physiotherapists indicated they wanted to use the ParkFit program in other patients. Multiple forward regression analysis resulted in a model with two variables: less baseline physical activity, and better mobility were associated with larger changes in levels of physical activity (R² = 38%). The program was effective in almost all subgroups. In women, most sedentary patients and patients with higher disease severity, the estimated effect size was largest.

Conclusion

We conclude that the ParkFit program was effective in almost all specific subgroups. Therapists and patients experienced no major hurdles. Suggestions for improvement are: (1) improve education for therapists with respect to theories about behavioral change; (2) formulate concrete and specific examples of exercise goals; and (3) pay more specific attention to patients with co morbidities, cognitive dysfunction and a lack of motivation during education