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Nasal dermoid cysts are surgically treated using external incision, open rhinoplasty, transnasal endoscopy, or combined approaches. It is unclear how these approaches differ with regard to the incidence of adverse events. We conducted a systematic review of studies on the surgical management of midline nasal dermoids. Following data abstraction, we carried out a series of single-arm meta-analyses to estimate summary risks of recurrence and combined adverse events (recurrence, revision, infection, or readmission) according to the surgical approach. Forty-three eligible studies published between 1958 and 2020 reported on 439 cases of nasal dermoid cysts. Treatment approaches included external incision (25 studies), rhinoplasty (15 studies), and transnasal endoscopy (5 studies). To our knowledge, no study has compared outcome incidence between the surgical approaches. External incision had the lowest summary incidence of both recurrence (1.78% [95% CI: 0.57%, 3.65%]) and combined adverse events (4.94% [95% CI: 2.72%, 7.77%]). Rhinoplasty had a higher incidence of recurrence (4.81% [95% CI: 0.91%, 11.6%]) and combined adverse events (8.32% [95% CI: 2.77%, 16.5%]), and transnasal endoscopy had the highest incidence of recurrence (the only reported adverse event; 7.89% [95% CI: 0%, 28.9%]). Our results suggest that the incidence of adverse events was lowest among patients who were subjected to external incision for nasal dermoid removal. Incidence was higher for patients who underwent rhinoplasty and the highest for patients who underwent transnasal endoscopy. Future work on this topic should include well-designed prospective studies that compare rates of adverse events and cosmetic outcomes between surgical approaches. [ABSTRACT FROM AUTHOR]

Climate and land-use change are modifying the availability of food and water resources, which is driving more wildlife to the wildland-urban interface. For many wildlife populations, use of these areas still requires habitat connectivity both within the interface and/or to wildland habitats. However, navigating these areas can be difficult due to human development and sensory pollutants, such as artificial night light. Determining how these components of urbanization influence the behaviors and functional connectivity of species is important for managing wildlife within these mixed-use landscapes. Here we used a movescape approach based on graph theory to characterize functional uses of the landscape using metrics for behavior, connectivity, and space use intensity. We found that mule deer (Odocoileus hemionus ; n = 43) functional uses of anthropogenic landscapes in the Intermountain West, USA, were dependent not only on physical barriers, terrain, and sensory factors, but also the local levels of light exposure and vegetative greenness. Remotely sensed artificial light levels had a strong influence on how mule deer used the landscape by reducing the intensity of use in the most illuminated areas given forage availability. In contrast, relatively high local light levels were associated with increased use intensity within less developed areas—highlighting the foraging tradeoffs for species using the wildland-urban interface. Corridor use was reduced in areas where road and housing density were higher, and within-corridor movement was faster when artificial light was high and vegetative greenness was low. Developing a more mechanistic understanding of how species functionally use the landscape in relation to features of urbanization can enhance conservation by delineating areas important for connectivity and foraging, while providing insights into how future development and climate change may alter movement and behavior. Spatially-explicit estimates of functional uses can directly guide management decisions to maintain species resiliency and improve land-use planning. [ABSTRACT FROM AUTHOR]

• This was a retrospective chart review of the safe interfacility transfers of 17 adult patients over 64 months. • Implementation of LifeFlight Nova Scotia's prone patient transport protocol provided a seamless transition of critical care while ensuring patients had access to the specialized lifesaving care they required. • Interfacility transport of prone patients by a dedicated critical care team is feasible with minimal adverse occurrences. This is a retrospective quality review of LifeFlight Nova Scotia's prone patient transport protocol. Electronic patient care records were queried for acute respiratory distress syndrome, prone position, proning, supine to prone, and prone to prone between February 2017 and June 2022. Eligible electronic patient care records were reviewed for demographics (sex, age, and weight); method of transports (ambulance, rotor wing, or fixed wing); duration of transports; mechanical ventilation parameters; medication infusions; arterial blood gases; occurrences of mild hypoxemia (any oxygen saturation [SpO 2 ] < 88% or decrease in SpO 2 > 5%); hypotension (any episode of MAP < 65 mm Hg); severe hypoxemia (any SpO 2 < 80% or decrease in SpO 2 > 10%); refractory hypotension (mean arterial pressure < 65 mm Hg not responsive to vasopressor/inotropes); cardiac arrests; and displacement of central lines, arterial lines, and endotracheal tubes. Seventeen prone patients were transported by ambulance, rotor wing, and fixed wing with 4 occurrences of mild hypotension, 4 occurrences of mild hypoxemia, and 1 occurrence of refractory hypotension. Interfacility transfer of prone patients by a dedicated critical care team is feasible with minimal adverse occurrences while ensuring patients have access to the specialized lifesaving care they require. [ABSTRACT FROM AUTHOR]

Mortality and morbidity from Non-Communicable Diseases (NCDs) in Africa are expected to worsen if the status quo is maintained. Emergency care settings act as a primary point of entry into the health system for a spectrum of NCD-related illnesses, however, there is a dearth of literature on this population. We conducted a systematic review assessing available evidence on epidemiology, interventions and management of NCDs in acute and emergency care settings in Kenya, the largest economy in East Africa and a medical hub for the continent. All searches were run on July 15, 2015 and updated on December 11, 2020, capturing concepts of NCDs, and acute and emergency care. The study is registered at PROSPERO (CRD42018088621). We retrieved a total of 461 references, and an additional 23 articles in grey literature. 391 studies were excluded by title or abstract, and 93 articles read in full. We included 10 articles in final thematic analysis. The majority of studies were conducted in tertiary referral or private/mission hospitals. Cancer, diabetes, cardiovascular disease and renal disease were addressed. Majority of the studies were retrospective, cross-sectional in design; no interventions or clinical trials were identified. There was a lack of access to basic diagnostic tools, and management of NCDs and their complications was limited. There is a paucity of literature on NCDs in Kenyan emergency care settings, with particular gaps on interventions and management. Opportunities include nationally representative, longitudinal research such as surveillance and registries, as well as clinical trials and implementation science to advance evidence-based, context-specific care. [ABSTRACT FROM AUTHOR]

Postoperative pneumonia is one of the most common complications after cardiac surgery, entailing increased patient morbidity, mortality, and health care burden. The primary aim of this study was to assess whether preoperative chlorhexidine mouthwash is associated with reduced postoperative pneumonia after cardiac surgery. A comprehensive systematic search of NLM Pubmed, Embase, Scopus, and Cumulative Index of Nursing and Allied Health was executed to include the studies since inception to June 27, 2017, which assessed the effects of preoperative chlorhexidine gluconate mouthwash on postoperative pneumonia. Studies were identified by 2 independent reviewers, and data were extracted using a predefined protocol. Random effects models were run to obtain risk ratios with 95% confidence intervals. Quality of evidence was evaluated using Grading of Recommendations Assessment, Development and Evaluation criteria. Postoperative pneumonia after cardiac surgery was the primary outcome of the study. Five studies including a cumulative of 2284 patients were included. A total of 1125 patients received preoperative chlorhexidine. Use of chlorhexidine gluconate was associated with reduced risk of postoperative pneumonia compared with the patients who did not receive it (risk ratio, 0.52; 95% confidence interval, 0.39-0.70; P <.001). No adverse effects from chlorhexidine gluconate mouthwash were reported by any of these studies. Among the patients receiving preoperative chlorhexidine mouthwash, the risk of postoperative pneumonia is reduced by approximately one-half; its adoption in preoperative protocols could help improve patient outcomes. Graphical Abstract summarizing the systematic review and meta-analysis of the use of preoperative chlorhexidine mouthwash to prevent postoperative pneumonia after cardiac surgery. A comprehensive literature search for key terms related to preoperative chlorhexidine mouthwash, postoperative pneumonia, and cardiac surgery revealed 5 studies that met the inclusion criteria. Use of chlorhexidine was significantly associated with reduced risk of postoperative pneumonia (risk ratio, 0.52; 95% confidence interval, 0.39-0.70; P <.001). [ABSTRACT FROM AUTHOR]

This study evaluates the impact of a coordinated effort by an urban pediatric hospital and its associated accountable care organization to reduce asthma-related emergency department (ED) and inpatient utilization by a large, countywide Medicaid patient population. Multiple evidence-based interventions targeting general pediatric asthma care and high health care utilizers were implemented using standardized quality improvement methodologies. Annual asthma ED and inpatient utilization rates by 2- to 18-year-old members of an accountable care organization living in the surrounding county (>140,000 eligible members in 2016), adjusted per 1000 children from 2008 through 2016, were analyzed using Poisson regression. We compared these ED utilization rates to national rates from 2006 to 2014. Asthma ED utilization fell from 18.1 to 12.9 visits/1000 children from 2008 to 2016, representing a 28.7% reduction, with an average annual decrease of 3.9% (P <.001), during a time when national utilization was increasing. Asthma inpatient utilization did not change significantly during the study period. Asthma-related ED utilization was significantly reduced in a large population of primarily urban, minority, Medicaid-insured children by implementing a multimodal asthma quality improvement program. With adequate support, a similar approach could be successful in other communities. [ABSTRACT FROM AUTHOR]

We report the case of a non-physician based critical care transport team (registered nurse and paramedic) that successfully initiated prone positioning of a severe acute respiratory distress patient prior to transport to an extracorporeal membrane oxygenation capable teaching hospital. With the increasing use of advanced treatments such as extracorporeal membrane oxygenation, prone positioning, and continuous renal replacement therapy for severe acute respiratory distress syndrome (ARDS), the necessity to transport these patients to specialized hospitals will correspondingly increase. Emergency Health Services Life Flight, the primary critical care transport program in Eastern Canada, developed a prone position protocol to meet this clinical need. Since the implementation of the protocol, we have successfully initiated prone positioning of 2 patients with ARDS before transport to an extracorporeal membrane oxygenation– and continuous renal replacement therapy–capable teaching hospital. This represents the first report of a nonphysician (registered nurse and paramedic) critical care team initiating prone positioning before transport. Consent for publication was only obtained in the second case, which we present here. [ABSTRACT FROM AUTHOR]

Background The comprehensive stage 2 procedure (CS2) follows initial hybrid stage 1 palliation for patients with single-ventricle physiology. The goal of this study was to describe CS2 outcomes and differences between survivors of CS2 (s-CS2) and nonsurvivors (nons-CS2). Method All patients in The Society of Thoracic Surgeons Congenital Heart Surgery Database who underwent CS2 as index operation from 2010 to 2016 were included. Preoperative, operative, and postoperative data were analyzed, stratified by operative mortality (in-hospital or within 30 days of the operation), with univariate comparisons using χ 2 , Fisher exact, or Wilcoxon rank sum tests. Results Of 209 patients (49 centers) who met inclusion criteria, 141 patients had the diagnosis of hypoplastic left heart syndrome. Overall operative mortality was 12.4% (26 of 209). s-CS2 had a lower prevalence of preoperative extracorporeal membrane oxygenation use (0.0% vs 7.7%, p = 0.02) and less frequently underwent concomitant tricuspid valve procedures at the time of the operation (1.1% vs 11.5%, p = 0.01) than nons-CS2. Postoperatively, the prevalence of any of six The Society of Thoracic Surgeons Congenital Heart Surgery Database major complications was higher in nons-CS2 than in s-CS2 (53.9% vs 23.0%, p < 0.01), including a higher prevalence of renal failure (7.7% vs 0.6%, p = 0.04) and postoperative extracorporeal membrane oxygenation use (46.2% vs 2.7%, p < 0.01). There were no other preoperative, operative, or postoperative differences between the two groups. Conclusions Operative mortality associated with the CS2 procedure is substantial, especially for patients receiving extracorporeal membrane oxygenation support after CS2. No obvious modifiable variables were noted between patients who died and those who survived. [ABSTRACT FROM AUTHOR]

Plastic pollution research on a global scale intensified considerably in the current decade; however, research efforts in the South Pacific are still lagging. Here, we report on microplastic contamination of intertidal and subtidal sediments in the Vava'u archipelago, Tonga. While providing the first baseline data of its type in Tonga, the study also advances methods and adjusts them for low-budget research. The methods were based on density separation of microplastics from the sediment using CaCl 2 , a high-density salt which due to its high solubility, low cost and availability. Once separated, microplastics were quantified by microscopic analysis and polymers characterized via FTIR spectroscopy. Microplastics in intertidal and subtidal sediments were found in concentrations of 23.5 ± 1.9 and 15.0 ± 1.9 particles L−1 of sediment, respectively. The dominant type of microplastics in both intertidal (85 %) and subtidal sediments (62 %) were fibres. • This study is the first microplastics research of the intertidal and subtidal sediments of Vava'u, Tonga. • Density separation of microplastics from the sediments was done using a CaCl 2 solution. • The dominant type of microplastics in both intertidal (85 %) and subtidal sediments (62 %) was fibres. • Intertidal microplastics were mainly larger than 1 mm, while the subtidal microplastics were generally smaller than 1 mm. [ABSTRACT FROM AUTHOR]

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Background: Audit and feedback can decrease variation and improve the quality of care in a variety of health care settings. There is a growing literature on audit and feedback in the emergency department (ED) setting. Because most studies have been small and not focused on a single clinical process, systematic assessment could determine the effectiveness of audit and feedback interventions in the ED and which specific characteristics improve the quality of emergency care.Objective: The objective of the study is to assess the effect of audit and feedback on emergency physician performance and identify features critical to success.Methods: We adhered to the PRISMA statement to conduct a systematic review of the literature from January 1994 to January 2014 related to audit and feedback of physicians in the ED. We searched Medline, EMBASE, PsycINFO, and PubMed databases. We included studies that were conducted in the ED and reported quantitative outcomes with interventions using both audit and feedback. For included studies, 2 reviewers independently assessed methodological quality using the validated Downs and Black checklist for nonrandomized studies. Treatment effect and heterogeneity were to be reported via meta-analysis and the I2 inconsistency index.Results: The search yielded 4332 articles, all of which underwent title review; 780 abstracts and 131 full-text articles were reviewed. Of these, 24 studies met inclusion criteria with an average Downs and Black score of 15.6 of 30 (range, 6-22). Improved performance was reported in 23 of the 24 studies. Six studies reported sufficient outcome data to conduct summary analysis. Pooled data from studies that included 41,124 patients yielded an average treatment effect among physicians of 36% (SD, 16%) with high heterogeneity (I2=83%).Conclusion: The literature on audit and feedback in the ED reports positive results for interventions across numerous clinical conditions but without standardized reporting sufficient for meta-analysis. Characteristics of audit and feedback interventions that were used in a majority of studies were feedback that targeted errors of omission and that was explicit with measurable instruction and a plan for change delivered in the clinical setting greater than 1 week after the audited performance using a combination of media and types at both the individual and group levels. Future work should use standardized reporting to identify the specific aspects of audit or feedback that drive effectiveness in the ED. [ABSTRACT FROM AUTHOR]

There is a wealth of valuable chemical information in publicly available databases for use by scientists undertaking drug discovery. However finite curation resource, limitations of chemical structure software and differences in individual database applications mean that exact chemical structure equivalence between databases is unlikely to ever be a reality. The ability to identify compound equivalence has been made significantly easier by the use of the International Chemical Identifier (InChI), a non-proprietary line-notation for describing a chemical structure. More importantly, advances in methods to identify compounds that are the same at various levels of similarity, such as those containing the same parent component or having the same connectivity, are now enabling related compounds to be linked between databases where the structure matches are not exact. [ABSTRACT FROM AUTHOR]

Abstract: Melanoma is frequently resistant to a wide range of chemotherapeutic and biologic agents. In its early stages, it is also very immunogenic and gives rise to both T cell and antibody responses. Killing of melanoma by T cells involves induction of apoptosis through the mitochondrial pathway and shares common apoptotic pathways to that induced by chemotherapy. We considered it was therefore possible that prolonged exposure to the immune system may generate escape variants that are resistant to apoptosis induced by the immune system or by chemotherapy. This hypothesis was tested by generating melanoma cells that were resistant to TNF-related apoptosis inducing ligand (TRAIL), which is one of the mediators of apoptosis used by the immune system. Melanoma cells selected in this way were found to be resistant to apoptosis induced by cisplatin, vincristine and a histone deacetylase inhibitor. Melanoma cells resistant to these agents had low levels of pro-apoptotic Bcl-2 (BH3 only) proteins and high levels of activated ERK1/2 and Akt signal pathways. Inhibition of the latter pathways partially overcame some of the resistance to the chemotherapy agents but not to TRAIL. These results support the view that selection by the immune system may in part be responsible for resistance of melanoma to some chemotherapy commonly used against melanoma. Further study of the resistant mechanisms involved may provide insights into new treatment approaches in melanoma. [Copyright &y& Elsevier]

Summary: Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) induces apoptosis in melanoma by interaction with death receptors TRAIL-R1 (DR4) or TRAIL-R2 (DR5) on melanoma cells or resists apoptosis by interaction with decoy receptors TRAIL-R3 (DcR1) or TRAIL-R4 (DcR2). Studies on cell lines suggest that there is a wide variation in TRAIL death receptor expression; however, their expression on excised human melanoma is not well documented. In view of this, we studied death receptor expression on melanomas using monoclonal antibodies specific for these receptors. Immunohistochemical staining for DR4, DR5, and DcR1/DcR2 was performed on formalin-fixed paraffin-embedded sections of 100 cases of primary melanoma, metastatic melanoma, and benign nevi. Percentage expressions of DR4 versus DR5 in benign nevi, primary melanoma, and melanoma metastases were 40% versus 90%, 69% versus 98%, and 55% versus 66%, respectively. There were significant differences in the mean percentage of DR5-positive cells between different groups of melanocytic lesions. Percent expression was higher in thin (≤1.0 mm) compared with thick primary melanoma (88.9% versus 66.9%), and expression was less in subcutaneous metastases (49%) and lymph node metastases (30.6%) (P < .005). Expression was also higher in compound nevi (57%) than dysplastic nevi (49%). DcR1/DcR2 was found in 75% of benign nevi, 62% of primary melanomas, and 74% melanoma metastases. The results showed a wide variation in the expression of death receptors for TRAIL between and within primary and metastatic melanoma and a decreased expression on the thick primary melanoma and metastatic melanoma. This suggests that melanoma may not respond to treatment with TRAIL unless given with agents that increase the expression of TRAIL death receptors. [Copyright &y& Elsevier]

Chemotherapy, biological agents or combinations of both have had little impact on survival of patients with metastatic melanoma. Advances in understanding the genetic changes associated with the development of melanoma resulted in availability of promising new agents that inhibit specific proteins up-regulated in signal cell pathways or inhibit anti-apoptotic proteins. Sorafenib, a multikinase inhibitor of the RAF/RAS/MEK pathway, elesclomol (STA-4783) and oblimersen (G3139), an antisense oligonucleotide targeting anti-apoptotic BCl-2, are in phase III clinical studies in combination with chemotherapy. Agents targeting mutant B-Raf (RAF265 and PLX4032), MEK (PD0325901, AZD6244), heat-shock protein 90 (tanespimycin), mTOR (everolimus, deforolimus, temsirolimus) and VEGFR (axitinib) showed some promise in earlier stages of clinical development. Receptor tyrosine-kinase inhibitors (imatinib, dasatinib, sunitinib) may have a role in treatment of patients with melanoma harbouring c-Kit mutations. Although often studied as single agents with disappointing results, new targeted drugs should be more thoroughly evaluated in combination therapies. The future of rational use of new targeted agents also depends on successful application of analytical techniques enabling molecular profiling of patients and leading to selection of likely therapy responders. [ABSTRACT FROM PUBLISHER]

The evaluation of interferons in the treatment of malignant melanoma has been mainly in the treatment of advanced disease using interferons as the sole agent or in combination with other agents. Studies of the value of interferons as adjuvant therapy in high-risk primary melanoma patients are necessary, but no results have been published to date. Human interferon alpha produces low response rates as a sole agent, but in combination with cimetidine, a 30% response rate has been achieved. Recombinant alpha interferons give responses of 15%-20% in advanced melanomas, and combination with cimetidine does not enhance the response rate. Recombinant alpha interferons have been used in combination with other interferons, cimetidine, monoclonal antibodies, and cytotoxics, with either no or small improvement in response rates. DTIC with recombinant interferon alpha-2a has been shown to produce objective response rates of 26%, with low toxicity and maintenance of quality of life. A randomized trial with DTIC as the sole agent, compared with combination treatment, is being conducted to determine the significance of this finding. [ABSTRACT FROM AUTHOR]

Background Pembrolizumab demonstrated robust antitumor activity and safety in the phase Ib KEYNOTE-001 study (NCT01295827) of advanced melanoma. Five-year outcomes in all patients and treatment-naive patients are reported herein. Patients whose disease progressed following initial response and who received a second course of pembrolizumab were also analyzed. Patients and methods Patients aged ≥18 years with previously treated or treatment-naive advanced/metastatic melanoma received pembrolizumab 2 mg/kg every 3 weeks, 10 mg/kg every 3 weeks, or 10 mg/kg every 2 weeks until disease progression, intolerable toxicity, or patient/investigator decision to withdraw. Kaplan–Meier estimates of overall survival (OS) and progression-free survival (PFS) were calculated. Objective response rate and PFS were based on immune-related response criteria by investigator assessment (data cut-off, September 1, 2017). Results KEYNOTE-001 enrolled 655 patients with melanoma; median follow-up was 55 months. Estimated 5-year OS was 34% in all patients and 41% in treatment-naive patients; median OS was 23.8 months (95% CI, 20.2–30.4) and 38.6 months (95% CI, 27.2–not reached), respectively. Estimated 5-year PFS rates were 21% in all patients and 29% in treatment-naive patients; median PFS was 8.3 months (95% CI, 5.8–11.1) and 16.9 months (95% CI, 9.3–35.5), respectively. Median response duration was not reached; 73% of all responses and 82% of treatment-naive responses were ongoing at data cut-off; the longest response was ongoing at 66 months. Four patients [all with prior response of complete response (CR)] whose disease progressed during observation subsequently received second-course pembrolizumab. One patient each achieved CR and partial response (after data cut-off). Treatment-related AEs (TRAEs) occurred in 86% of patients and resulted in study discontinuation in 7.8%; 17% experienced grade 3/4 TRAE. Conclusions This 5-year analysis of KEYNOTE-001 represents the longest follow-up for pembrolizumab to date and confirms the durable antitumor activity and tolerability of pembrolizumab in advanced melanoma. Clinical Trial Registry ClinicalTrials.gov, NCT01295827. [ABSTRACT FROM AUTHOR]

Background Pembrolizumab is a potent humanised monoclonal antibody against PD-1 that has shown efficacy and safety in patients with advanced solid tumours and haematological malignancies. Methods KEYNOTE-001 (NCT01295827) was a multicohort phase 1 study that included 411 patients with advanced melanoma, including 221 who previously received ipilimumab (IPI-T) and 190 who were ipilimumab naive (IPI-N). Patients received pembrolizumab at 10 mg/kg every 3 weeks (Q3W), 2 mg/kg Q3W, or 10 mg/kg Q2W. Response was assessed every 12 weeks per RECIST v1.1 by independent central review and per immune-related response criteria (irRC) by the investigator. Findings As of the April 18 2014, median follow-up duration for all patients was 18 months (range 12–28). The 360 patients with measurable disease per central review at baseline had objective response/disease control rates per RECIST of 34%/54% (29%/54% in IPI-T patients, 39%/55% in IPI-N patients). By irRC, objective response/disease control rates were 39%/64% (34%/65% in IPI-T patients, 45%/64% in IPI-N patients). 57 patients who had progressive disease by RECIST had non-progressive disease by irRC. Responses were durable, with 81% ongoing at analysis (median response duration not reached; range, 6+ to 98+ weeks). Pembrolizumab showed antitumour benefit at all doses and schedules regardless of ECOG performance status, previous IPI, or LDH levels. Per RECIST, 6-month PFS was 45% (42% for IPI-T, 48% for IPI-N). Median overall survival was 25.9 months, with a 69% 1-year overall survival (65% for IPI-T, 74% for IPI-N). Pembrolizumab was safe and well tolerated, with 14% of all patients experiencing drug-related grade 3/4 adverse events (15% IPI-N, 14% IPI-T) and only 5% discontinuing pembrolizumab because of a drug-related adverse events (6% IPI-N, 5% IPI-T). There were no treatment-related deaths. Interpretation Pembrolizumab provides a favourable benefit-risk profile in both IPI-T and IPI-N patients, suggesting it could be a promising treatment option for all patients with advanced melanoma. [ABSTRACT FROM AUTHOR]

Immunotherapy of metastatic melanoma consists of various approaches leading to specific or non-specific immunomodulation. The use of FDA-approved interleukin (IL)-2 alone, in combination with interferon α, and/or with various chemotherapeutic agents (biochemotherapy) is associated with significant toxicity and poor efficacy that does not improve overall survival of 96% of patients. Many studies with allogeneic and autologous vaccines have demonstrated no clinical benefit, and some randomised trials even showed a detrimental effect in the vaccine arm. The ongoing effort to develop melanoma vaccines based on dendritic cells and peptides is driven by advances in understanding antigen presentation and processing, and by new techniques of vaccine preparation, stabilisation and delivery. Several agents that have shown promising activity in metastatic melanoma including IL-21 and monoclonal antibodies targeting cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4) or CD137 are discussed. Recent advances of intratumour gene transfer technologies and adoptive immunotherapy, which represents a promising although technically challenging direction, are also discussed. [ABSTRACT FROM PUBLISHER]

Biomarkers are tumour- or host-related factors that correlate with tumour biological behaviour and patient prognosis. High-throughput analytical techniques—DNA and RNA microarrays—have identified numerous possible biomarkers, but their relevance to melanoma progression, clinical outcome and the selection of optimal treatment strategies still needs to be established. The review discusses a possible molecular basis for predictive tissue biomarkers such as melanoma thickness, ulceration and mitotic activity, and provides a list of promising new biomarkers identified from tissue microarrays that needs confirmation by independent, prospectively collected clinical data sets. In addition, common predictive serum biomarkers—lactate dehydrogenase, S100B and melanoma-inhibiting activity—as well as selected investigational serum biomarkers such as TA90IC and YKL-40 are also reviewed. A more accurate, therapeutically predictive classification of human melanomas and selection of patient populations that would profit from therapeutic interventions are among the major challenges expected to be addressed in the future. [ABSTRACT FROM PUBLISHER]

The lack of effective drugs in stage IV melanoma has impacted the effectiveness of adjuvant therapies in stage II/III disease. To date, chemotherapy, immunostimulants and vaccines have been used with minimal success. Interferon (IFN) has shown an effect on relapse-free survival (RFS) in several clinical trials; however, without a clinically significant effect on overall survival (OS). A recently conducted meta-analysis demonstrated prolongation of disease-free survival (DFS) in 7% and OS benefit in 3% of IFN-treated patients when compared with observation-only patients. There were no clear differences for the dose and duration of treatment observed. Observation is still an appropriate control arm in adjuvant clinical trials. Regional differences exist in Europe in the adjuvant use of IFN. In Northwest Europe, IFN is infrequently prescribed. In Central and Mediterranean Europe, dermatologists commonly prescribe low-dose IFN therapy for AJCC stage II and III disease. High-dose IFN regimens are not commonly used. The population of patients that may benefit from IFN needs to be further characterised, potentially by finding biomarkers that can predict response. Such studies are ongoing. [ABSTRACT FROM PUBLISHER]