Prospective cohort study of ultrasound surveillance of regional lymph nodes in patients with intermediate-risk cutaneous melanoma.

BACKGROUND: For patients with intermediate-thickness melanoma, surveillance of regional lymph node basins by clinical examination alone has been reported to result in a larger number of lymph nodes involved by melanoma than if patients had initial sentinel node biopsy and completion dissection. This may result in worse regional control. A prospective study of both regular clinical examination and ultrasound surveillance was conducted to assess the effectiveness of these modalities. METHODS: Between 2010 and 2014, patients with melanoma of thickness 1·2-3·5 mm who had under-gone wide local excision but not sentinel node biopsy were recruited to a prospective observational study of regular clinical and ultrasound nodal surveillance. The primary endpoint was nodal burden within a dissected regional lymph node basin. Secondary endpoints included locoregional or distant relapse, progression-free and overall survival. RESULTS: Ninety patients were included in the study. After a median follow-up of 52 months, ten patients had developed nodal relapse as first recurrence, four had locoregional disease outside of an anatomical nodal basin as the first site of relapse and six had relapse with distant disease. None of the patients who developed relapse within a nodal basin presented with unresectable nodal disease. The median number of involved lymph nodes in patients undergoing lymphadenectomy for nodal relapse was 1 (range 1-2; mean 1·2). CONCLUSION: This study suggests that ultrasound surveillance of regional lymph node basins is safe for patients with melanoma who undergo a policy of nodal surveillance.

Neurotoxicity from immune-checkpoint inhibition in the treatment of melanoma: a single centre experience and review of the literature.

Background: Treatment with immune checkpoint inhibitors (ICPi) has greatly improved survival for patients with advanced melanoma in recent years. Anti-CTLA-4 and anti-PD1 antibodies have been approved following large Phase III trials. Immune-related neurological toxicity of varying severity has been reported in the literature. The cumulative incidence of neurotoxicity among ipilimumab, nivolumab and pembrolizumab is reported as <1% in published clinical trials. We aimed to identify the incidence of neurotoxicity in our institution across anti-CTLA4 and anti-PD-1 antibodies, including the combination of ipilimumab with nivolumab. We also review the existing literature and propose an investigation and management algorithm. Methods: All patients with advanced melanoma treated with ipilimumab, nivolumab, pembrolizumab or the combination of ipilimumab and nivolumab (ipi + nivo), managed at the Royal Marsden Hospital between September 2010 and December 2015, including patients on (published) clinical trials were included. Medical records for each patient were reviewed and information on neurotoxicity recorded. A systematic search strategy was performed to collate existing reports of neurological toxicity. Results: In total, 413 immunotherapy treatment episodes in 352 patients were included, with median follow-up of 26.7 months. Ten cases of neurotoxicity were recorded, affecting 2.8% of patients overall, ranging from grade 1 to 4, affecting both central and peripheral nervous systems. A rate of 14% was noted with ipi + nivo. Three of five patients commenced on corticosteroids responded to these. Six patients had made a full recovery at the time of reporting. A favorable radiological response was found in 7 of the 10 cases. Unusual presentations are described in detail. Conclusions: Neurological toxicity is not uncommon, and may be more frequent in patients treated with combination ipi + nivo. Patterns of presentation and response to treatment are varied. A prompt and considered approach is required to optimize outcomes in this group of patients.

Evaluation of recombinant Salmonella expressing the flagellar protein fliC for persistence and enhanced antibody response in commercial turkeys.

Salmonella enterica serovar Enteritidis (SE) is one of the most common causes of human foodborne illness in the United States. Previous research indicates that antibodies against the fliC protein can provide protection against Salmonella challenge in mice. To generate a vaccine that effectively protects poultry against multiple Salmonella serotypes, novel attenuated strains of SE were developed to express a fliC peptide sequence on the outer membrane protein lamB in association with an M2e (marker) epitope. In 3 separate trials, poults were immunized with 10(7) to 10(8) cfu/poult of the appropriate recombinant Salmonella strains (ΔSE-M2e or ΔSE-M2e-fliC) via oral gavage on the day of hatch and again on d 21 posthatch. Liver, spleen, and cecal tonsils were aseptically removed on d 7, 14, 21, 28, 35, and 42 posthatch for detection of Salmonella, and blood samples were obtained at these same time points for determination of an M2e-specific antibody response. In all 3 trials, the ΔSE-M2e-fliC strain exhibited significantly less invasion of the liver and spleen at d 7 and 14 when compared with ΔSE-M2e or SE phage type 13A (P < 0.05). Similarly, colonization of the cecal tonsils was decreased in the poults immunized with the ΔSE-M2e-fliC strain. By d 21, the ΔSE-M2e-fliC strain exhibited a significantly higher M2e-specific antibody response when compared with the negative control and SE phage type 13A groups (P < 0.05). However, no significant differences in M2e-specific antibody responses were observed between the ΔSE candidate vaccine strains throughout the study. Overall, these data suggest that oral live attenuated Salmonella-vectored vaccines expressing a fliC peptide sequence are able to elicit a humoral immune response in commercial poults and may contribute to a reduction in Salmonella organ invasion and colonization.

Evaluation of recombinant Salmonella expressing CD154 for persistence and enhanced antibody response in commercial turkeys.

Foodborne illness due to Salmonella is a worldwide public health concern and epidemiological evidence has identified poultry and poultry products as a significant source of human Salmonella infection. To discover an effective vaccine that protects poultry against multiple Salmonella serotypes, several novel attenuated Salmonella Enteritidis strains (DeltaSE) were developed to express variations of a potential immune-enhancing CD154 peptide sequence on the outer membrane protein lamB in association with a M2e (marker) epitope. The 3 CD154 peptide sequences evaluated in this study correspond to those naturally occurring in turkeys, humans, and chickens. In 3 separate trials, poults were immunized with 10(7) to 10(8) cfu/poult of the appropriate recombinant Salmonella strains (DeltaSE-M2e, DeltaSE-M2e-T/CD154, DeltaSE-M2e-H/CD154, DeltaSE-M2e-C/CD154) via oral gavage on day of hatch and again on 21 d posthatch. Liver, spleen, and cecal tonsils were aseptically removed on d 7, 14, 21, 28, 35, and 42 posthatch for detection of Salmonella and blood samples were obtained at these same time points for determination of an M2e-specific antibody response. In all 3 trials, DeltaSE strains exhibited significantly less invasion of the liver and spleen at d 7 when compared with Salmonella Enteritidis phage type 13A (P < 0.05). In 2 of the 3 trials, the DeltaSE strains expressing a CD154 peptide sequence further decreased invasion of the liver and spleen. Similarly, colonization of the cecal tonsils was also decreased in the poults immunized with the DeltaSE strains. However, there were no differences in colonization or invasion due to the amino acid sequence of the CD154 insert in all 3 trials. By d 21, the DeltaSE strains exhibited a significantly higher M2e-specific antibody response when compared with the negative control and SE13A groups (P < 0.05). However, no significant differences in M2e-specific antibody responses were observed between any of the DeltaSE candidate vaccine strains expressing CD154 throughout the study. Overall, these data suggest that oral live attenuated Salmonella-vectored vaccines expressing a foreign peptide sequence are able to elicit a humoral immune response in commercial poults and may contribute to a reduction in Salmonella organ invasion and colonization.

Transesophageal echocardiography: a sonographer's perspective.

Clinical transesophageal echocardiography is increasingly being applied for the evaluation of numerous functional and anatomic cardiac abnormalities. This new technology has opened an area of invasive ultrasonography that has changed and expanded the role of the cardiac sonographer. The sonographer is essential for the implementation and performance of this recent advance in echocardiography.

The impact of shared medical records on smoking awareness and behavior in ambulatory care.

In a randomized controlled trial of sharing medical records with ambulatory adults as part of periodic health examinations, 193 patients (experimental group; 37 smokers) received copies of their medical records while 208 patients (control group; 50 smokers) did not. Awareness of smoking as a health problem and smoking behavior were assessed two weeks and six months later. At two weeks, 46% of experimental group smokers indicated that smoking was a major health problem, compared with 21% of the control group (p less than 0.02), and 43% of the experimental group had quit or reduced smoking, compared with 20% of the control group (p less than 0.02). At six months smoking problem awareness was not significantly different (33% experimental group vs. 14% control group, p = NS), but 65% of the experimental group had quit or reduced compared with 29% of the control group (p less than 0.04). Sharing medical records with smokers after periodic health examinations is effective in enhancing patient awareness of smoking as a health problem and beginning the process of changing smoking behavior.

Preadmission programs: development, implementation and evaluation.

Preparation of children for hospitalization is utilized to mitigate the stresses which may accompany the experience. Preadmission programs provide preparation for the patient and family on a prehospital basis. The authors describe the development of family-centered, developmentally based programs which foster continuity and consistency in a large, pediatric tertiary care setting. Implementation and evaluation of the programs which contribute to quality patient care are discussed.

Establishing the psychiatric liaison nurse role: collaboration with the nurse administrator.

By helping patients, families, the hospital staff deal with the emotional effects of illness, the psychiatric liaison nurse plays a significant role in patients' healing. Since this type of role may be new to the organization, the psychiatric nurse and the nursing administrator must work in tandem to ensure successful role development and entry into the hospital system, both of which are crucial to the effectiveness of the liaison nurse. In our clinical experience, these issues need careful consideration and attention by both nurse administrators and psychiatric liaison nurses. We have attempted to provide practical considerations for facilitating the success of a psychiatric liaison nurse in the hospital system and justifying the value of this role.