Synovial Fluid Cutibacterium acnes Antigen Is Detected Among Shoulder Samples with High Inflammation and Early Culture Growth.

BACKGROUND: An emerging paradigm suggests that positive Cutibacterium acnes shoulder cultures can result from either true infection or contamination, with true infections demonstrating a host inflammatory response and early culture growth. This clinical retrospective study examines the relationship between C. acnes antigen, C. acnes culture results, and inflammation. METHODS: From January 2021 to July 2023, 1,365 periprosthetic synovial fluid samples from 347 institutions were tested for shoulder infection at a centralized clinical laboratory. A biomarker scoring system based on the 2018 International Consensus Meeting (ICM) definition was utilized to assign each sample an inflammation score. Associations between inflammation, culture results, and C. acnes antigen results were assessed utilizing cluster and correlation analyses. RESULTS: Of 1,365 samples, 1,150 were culture-negative and 215 were culture-positive (94 C. acnes and 121 other organisms). Among the 94 C. acnes culture-positive samples, unsupervised clustering revealed 2 distinct sample clusters (silhouette coefficient, 0.83): a high-inflammation cluster (n = 67) and a low-inflammation cluster (n = 27). C. acnes antigen levels demonstrated moderate-strong positive correlation with inflammation (Spearman ρ, 0.60), with 166-fold higher levels of C. acnes antigen in high-inflammation samples (16.6 signal/cutoff [S/CO]) compared with low-inflammation samples (0.1 S/CO) (p < 0.0001). The days to C. acnes culture positivity demonstrated weak-inverse correlation with inflammation (Spearman ρ = -0.38), with 1.5-fold earlier growth among the 67 high-inflammation samples (6.7 compared with 10.4 days; p < 0.0001). Elevated C. acnes antigen was observed in only 4 (0.38%) of 1,050 low-inflammation culture-negative samples and in only 5 (4.9%) of 103 high-inflammation non-C. acnes-positive cultures. However, 19.0% of high-inflammation, culture-negative samples demonstrated elevated C. acnes antigen. CONCLUSIONS: Synovial fluid C. acnes antigen was detected among shoulder samples with high inflammation and early culture growth, supporting the emerging paradigm that these samples represent true infection. Future research should explore antigen testing to differentiate contamination from infection and to identify culture-negative C. acnes infections. LEVEL OF EVIDENCE: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Achieving High Accuracy in Predicting the Probability of Periprosthetic Joint Infection From Synovial Fluid in Patients Undergoing Hip or Knee Arthroplasty: The Development and Validation of a Multivariable Machine Learning Algorithm.

Background and objective The current periprosthetic joint infection (PJI) diagnostic guidelines require clinicians to interpret and integrate multiple criteria into a complex scoring system. Also, PJI classifications are often inconclusive, failing to provide a clinical diagnosis. Machine learning (ML) models could be leveraged to reduce reliance on these complex systems and thereby reduce diagnostic uncertainty. This study aimed to develop an ML algorithm using synovial fluid (SF) test results to establish a PJI probability score. Methods We used a large clinical laboratory's dataset of SF samples, aspirated from patients with hip or knee arthroplasty as part of a PJI evaluation. Patient age and SF biomarkers [white blood cell count, neutrophil percentage (%PMN), red blood cell count, absorbance at 280 nm wavelength, C-reactive protein (CRP), alpha-defensin (AD), neutrophil elastase, and microbial antigen (MID) tests] were used for model development. Data preprocessing, principal component analysis, and unsupervised clustering (K-means) revealed four clusters of samples that naturally aggregated based on biomarker results. Analysis of the characteristics of each of these four clusters revealed three clusters (n=13,133) with samples having biomarker results typical of a PJI-negative classification and one cluster (n=4,032) with samples having biomarker results typical of a PJI-positive classification. A decision tree model, trained and tested independently of external diagnostic rules, was then developed to match the classification determined by the unsupervised clustering. The performance of the model was assessed versus a modified 2018 International Consensus Meeting (ICM) criteria, in both the test cohort and an independent unlabeled validation set of 5,601 samples. The SHAP (SHapley Additive exPlanations) method was used to explore feature importance. Results The ML model showed an area under the curve of 0.993, with a sensitivity of 98.8%, specificity of 97.3%, positive predictive value (PPV) of 92.9%, and negative predictive value (NPV) of 99.8% in predicting the modified 2018 ICM diagnosis among test set samples. The model maintained its diagnostic accuracy in the validation cohort, yielding 99.1% sensitivity, 97.1% specificity, 91.9% PPV, and 99.9% NPV. The model's inconclusive rate (diagnostic probability between 20-80%) in the validation cohort was only 1.3%, lower than that observed with the modified 2018 ICM PJI classification (7.4%; p<0.001). The SHAP analysis found that AD was the most important feature in the model, exhibiting dominance among >95% of "infected" and "not infected" diagnoses. Other important features were the sum of the MID test panel, %PMN, and SF-CRP. Conclusions Although defined methods and tools for diagnosis of PJI using multiple biomarker criteria are available, they are not consistently applied or widely implemented. There is a need for algorithmic interpretation of these biomarkers to enable consistent interpretation of the results to drive treatment decisions. The new model, using clinical parameters measured from a patient's SF sample, renders a preoperative probability score for PJI which performs well compared to a modified 2018 ICM definition. Taken together with other clinical signs, this model has the potential to increase the accuracy of clinical evaluations and reduce the rate of inconclusive classification, thereby enabling more appropriate and expedited downstream treatment decisions.

Complications of Influenza A or B Virus Infection in Individuals With SCN1A-Positive Dravet Syndrome.

BACKGROUND AND OBJECTIVES: To determine the frequency and spectrum of complications of influenza infection in individuals with SCN1A-positive Dravet syndrome (SCN1A-DS). METHODS: Individuals with SCN1A-DS were identified in neurologists' care at 2 hospitals in Melbourne, Australia, with additional searches of EEG databases, the Victorian PAEDS FluCan influenza database, and the University of Melbourne Epilepsy Genetics Research Program database. Medical records were searched and families questioned to identify individuals who had an influenza infection; reported infections were confirmed by pathology report. For these individuals, we obtained baseline clinical characteristics and clinical details of the influenza infection. RESULTS: Twenty-one of 82 individuals (26%) had 24 documented influenza infections (17 influenza A and 7 influenza B) at age 0.5-25 years (median 4 years). All presented to hospital, 18/24 (75%) for status epilepticus or seizure exacerbations. Recovery was prompt in 18/24 (75%) infections, delayed but complete in 1/24 (4%) and incomplete in 5/24 (21%). One child died from influenza pneumonia, and long-term neurologic sequelae were seen with 4 infections. These individuals were poorly responsive after termination of status epilepticus. Brain imaging in 2 showed cerebral edema and 1 also having imaging features of laminar necrosis. All have ongoing neurologic deficits compared with their baseline, 1 having profound global impairment. DISCUSSION: Our data show that patients with SCN1A-DS are highly susceptible to neurologic complications during and severe sequelae after influenza infection, including moderate to severe persistent neurologic impairments and death. Safe administration of the seasonal influenza vaccine should be prioritized for this population.

Assessment of the inter-rater agreement of corneal cytology and culture findings in canine ulcerative keratitis.

OBJECTIVES: To assess the inter-rater agreement of corneal cytology findings in canine ulcerative keratitis by veterinary surgeons of different training levels and the agreement of corneal cytology with culture. MATERIALS AND METHODS: Dogs with progressive ulcerative keratitis were prospectively recruited for corneal cytology and culture. Corneal cytology slides were reviewed by veterinary surgeons of different training levels (three general practitioners, three ophthalmologists and three pathologists). The inter-rater agreement of cytology findings and agreement of cytology with culture was assessed using the kappa measure of agreement. RESULTS: The study included 145 corneal cytology samples from 143 dogs (145 eyes) with progressive ulcerative keratitis. Positive cultures were obtained from 81 of 145 (56%) eyes. The most commonly isolated pathogens were Streptococcus canis, Pseudomonas aeruginosa and Staphylococcus pseudintermedius. The results demonstrated increased inter-rater agreement of corneal cytology and increased agreement with culture with increased ocular pathology expertise (pathologists > ophthalmologists > general practitioners). CLINICAL SIGNIFICANCE: This study provides important information about the diagnostic value of corneal cytology in canine ulcerative keratitis and the most common pathogens involved in such cases in the UK. Based on the results of this study, cytology findings should be interpreted in conjunction with the expertise of the observer. For maximal pathogen identification, both cytology and culture should be considered.

Multiple paternity in a lek mating system: Females mate multiply when they choose inexperienced sires.

Multiple mating by females is common and often driven by social constraints on female mate choice. However, females mate with multiple males even in systems without these social constraints and rates of multiple mating tend to be highly variable within and between populations. In lek mating systems, females are able to assess multiple males and their choice is unrestricted by pair bonds or the need for biparental care, yet some females mate with multiple males. To better understand the factors affecting variation in multiple mating, we investigated the occurrence of multiple paternity within clutches in a highly polygynous lek mating system. Using long-term data on genetic paternity, survival, social status and individual age from a population of lance-tailed manakins Chiroxiphia lanceolata, a species where males lek in cooperative alpha-beta pairs, we tested five non-exclusive hypotheses about the causes of variation in multiple mating and its benefits in females. We found that inexperienced males, including new alphas and rare beta sires, were disproportionately likely to share paternity when they sired any chicks. In contrast, female age (experience) was unrelated to multiple paternity. Multiple mating did not result in higher reproductive success or reduced variance in success for females, and there were neither consistently promiscuous females nor males that consistently shared paternity. The occurrence of multiple paternity in this lek mating system was best explained by female choice related to male characteristics that change with male experience. Our results support the hypothesis that there is a developmental component to the occurrence of multiple mating, and suggest females choose to mate multiply when their choices are not optimal.

Weight bias internalization in a commercial weight management sample: prevalence and correlates.

OBJECTIVE: Weight bias internalization (WBI) is associated with poor weight-related health. The purpose of this study was to identify the prevalence and correlates of WBI in a large sample of adults in a commercial weight management programme. METHODS: WW (the new Weight Watchers) members participated in an online survey. Participants (N = 18,769) completed the 10-item Weight Bias Internalization Scale - Modified (WBIS-M) and the Weight Self-Stigma Questionnaire (WSSQ). Participants reported details about weight-stigmatizing experiences, including the onset, frequency and distress, and interpersonal sources of weight stigma. Participants self-reported their demographics, weight history, and height and weight (to compute body mass index [BMI]). RESULTS: Weight bias internalization was relatively high compared with the general population (mean WBIS-M score = 4.3 ± 1.4; mean WSSQ total score = 35.2 ± 9.7). WBI was higher among participants who were female, younger and had higher BMIs (p < 0.001) and lower among those who were Black and were widowed or had a romantic partner (p < 0.001). Onset of weight stigma in childhood and young adulthood, and recent distress due to weight stigma, predicted higher WBI. Extended family and school sources of weight stigma had weaker associations with WBI than did other interpersonal sources. CONCLUSIONS: Weight bias was internalized by a significant proportion of adults enrolled in a commercial weight management programme. A phenotype of WBI includes demographic characteristics and the timing and sources of weight stigma.

A randomized controlled trial of lorcaserin and lifestyle counselling for weight loss maintenance: changes in emotion- and stress-related eating, food cravings and appetite.

Anti-obesity medication may help people maintain diet-induced reductions in appetite. The present exploratory analysis assessed the effects of lorcaserin on changes at 24 weeks post-randomization in emotion- and stress-related eating, food cravings and other measures of appetite (i.e. binge eating, cognitive restraint, disinhibition, hunger, preoccupation with eating and fullness). The parent study investigated the efficacy of combined lorcaserin and behavioural treatment in facilitating weight loss maintenance (WLM) in 137 adults (mean age = 46.1 years, 86.1% female, 68.6% black) who had lost ≥5% of initial weight during a 14-week, low-calorie diet (LCD) run-in. Participants were randomly assigned to lorcaserin or placebo and were provided with group WLM counselling sessions. Emotion- and stress-related eating, food cravings and appetite were measured at the start of the LCD (week -14), randomization (0) and week 24. From randomization, lorcaserin-treated participants had significantly greater improvements in emotion- and stress-related eating compared to placebo-treated participants (P = 0.04). However, groups did not differ significantly after randomization in changes in the frequency of food cravings, binge eating or other measures of appetite (Ps > 0.05). Compared to placebo, lorcaserin may improve emotion- and stress-related eating.

Weight bias internalization and health: a systematic review.

A robust literature has documented the negative health effects of being the target of weight bias. Weight bias internalization (WBI) occurs when individuals apply negative weight stereotypes to themselves and self-derogate because of their body weight. Compared with experiences of weight bias, less is known about the relationship between WBI and mental and physical health, although more literature on this topic has emerged in recent years. The current systematic review identified 74 studies assessing the relationship between WBI and health and interventions designed to reduce WBI and improve health. Over half of identified studies were published from 2016 to 2017. Results showed strong, negative relationships between WBI and mental health outcomes. Fewer studies have examined the relationship between WBI and physical health, and results were less consistent. Key directions for future research are highlighted, including the need for prospective and experimental studies with greater sample diversity.

Everyday discrimination in a racially diverse sample of patients with obesity.

Weight discrimination affects a significant proportion of individuals with obesity and contributes to poor mental and physical health. Prior research on weight discrimination has been limited by a lack of racial diversity in samples and has not considered other potential forms of discrimination that individuals with obesity may experience. The current study assessed different reasons for discrimination in a racially diverse sample of treatment-seeking individuals with obesity (N = 122, 66.4% black, mean body mass index = 38.5 ± 6.2 kg/m2 ). Results showed that over half of participants reported experiencing at least one form of repeated discrimination, and 30% reported two or more reasons for discrimination. Race and weight were the most commonly reported reasons for repeated, everyday instances of discrimination. Among participants who reported experiencing weight discrimination (28.7%), over 80% reported experiencing at least one other form of discrimination, with 60% reporting discrimination due to race. These findings indicate that individuals with obesity may face multiple forms of discrimination in their daily lives. Further research is needed to understand how all forms of discrimination contribute to obesity-related health problems.

Adult meerkats modify close call rate in the presence of pups.

In animals, signaling behavior is often context-dependent, with variation in the probability of emitting certain signals dependent on fitness advantages. Senders may adjust signaling rate depending on receiver identity, presence of audiences, or noise masking the signal, all of which can affect the benefits and costs of signal production. In the cooperative breeding meerkat Suricata suricatta, group members emit soft contact calls, termed as "close calls", while foraging in order to maintain group cohesion. Here, we investigated how the close calling rate during foraging was affected by the presence of pups, that produce continuous, noisy begging calls as they follow older group members. Adults decreased their overall close call rate substantially when pups were foraging with the group in comparison to periods when no pups were present. We suggest this decrease was likely due to a masking effect of the loud begging calls, which makes the close call function of maintaining group cohesion partly redundant as the centrally located begging calls can be used instead to maintain cohesion. There was some support that adults use close calls strategically to attract specific pups based on fitness advantages, that is, as the philopatric sex, females should call more than males and more to female pups than male pups. Dominant females called more than dominant males when a pup was in close proximity, while subordinates showed no sex-based differences. The sex of the nearest pup did not affect the calling rate of adults. The study shows that meerkats modify their close call production depending on benefits gained from calling and provides an example of the flexible use of one calling system in the presence of another, here contact calls versus begging calls, within the same species.

Visual portrayals of obesity in health media: promoting exercise without perpetuating weight bias.

Health education campaigns for preventing and reducing obesity often contain weight-stigmatizing visual content, which may have unintended negative health consequences. The goal of the present research was to identify non-stigmatizing visual content for health education materials that can promote exercise among people of diverse weight statuses. An online sample of 483 US women viewed: (i) a woman with obesity portrayed stereotypically; (ii) a woman with obesity exercising; (iii) a woman with obesity portrayed neutrally; or (iv) a lean woman exercising. Race of the models pictured was randomized (White or Black). Participants completed measures of weight bias and exercise behavior and attitudes, and provided information about their weight status. Analysis of covariance revealed that responses to stereotypical and exercise images varied by participant weight status. Across participants, neutral obesity portrayals elicited lower expressions of weight-biased attitudes and higher reports of exercise liking/comfort. Among non-overweight participants, images portraying women with obesity stereotypically or counter-stereotypically produced greater endorsement of negative stereotypes than control, lean images. No effects of model race were found. These findings suggest that the public responds differently to visual portrayals of obesity depending on weight status, and neutral portrayals may be an effective route toward promoting exercise without perpetuating stigma.

Three-dimensional assessment of hand outcome.

INTRODUCTION: Patient reported outcome measures are central to National Health Service quality of care assessments. This study investigated the benefit of elective hand surgery by the simultaneous analysis of pain, function and appearance, using a three-dimensional (3D) graphical model for evaluating and presenting outcome. METHODS: A total of 188 patients scheduled for surgery completed pre- and postoperative questionnaires grading the severity of their pain, dysfunction and deformity of their hand(s). Scores were plotted on a 3D graph to demonstrate the degree of 'normalisation' following surgery. RESULTS: Surgical groups included: nerve compression (n=53), Dupuytren's disease (n=51), trigger finger (n=20), ganglion (n=17) or other lump (n=21), trapeziometacarpal joint osteoarthritis (n=10), rheumatoid disease (n=5) and other pathology (n=13). A significant improvement towards normality was seen after surgery in each group except for patients with rheumatoid disease. CONCLUSIONS: This study provides a simple, visual representation of hand surgery outcome by plotting patient scores for pain, function and appearance simultaneously on a 3D graph.

Implementation of a personnel reliability program as a facilitator of biosafety and biosecurity culture in BSL-3 and BSL-4 laboratories.

In late 2010, the National Biodefense Analysis and Countermeasures Center (NBACC) implemented a Personnel Reliability Program (PRP) with the goal of enabling active participation by its staff to drive and improve the biosafety and biosecurity culture at the organization. A philosophical keystone for accomplishment of NBACC's scientific mission is simultaneous excellence in operations and outreach. Its personnel reliability program builds on this approach to: (1) enable and support a culture of responsibility based on human performance principles, (2) maintain compliance with regulations, and (3) address the risk associated with the insider threat. Recently, the Code of Federal Regulations (CFR) governing use and possession of biological select agents and toxins (BSAT) was amended to require a pre-access suitability assessment and ongoing evaluation for staff accessing Tier 1 BSAT. These 2 new requirements are in addition to the already required Federal Bureau of Investigation (FBI) Security Risk Assessment (SRA). Two years prior to the release of these guidelines, NBACC developed its PRP to supplement the SRA requirement as a means to empower personnel and foster an operational environment where any and all work with BSAT is conducted in a safe, secure, and reliable manner.

Relative effects of juvenile and adult environmental factors on mate attraction and recognition in the cricket, Allonemobius socius.

Finding a mate is a fundamental aspect of sexual reproduction. To this end, specific-mate recognition systems (SMRS) have evolved that facilitate copulation between producers of the mating signal and their opposite-sex responders. Environmental variation, however, may compromise the efficiency with which SMRS operate. In this study, the degree to which seasonal climate experienced during juvenile and adult life-cycle stages affects the SMRS of a cricket, Allonemobius socius (Scudder) (Orthoptera: Gryllidae) was assessed. Results from two-choice behavioral trials suggest that adult ambient temperature, along with population and family origins, mediate variation in male mating call, and to a lesser extent directional response of females for those calls. Restricted maximum-likelihood estimates of heritability for male mating call components and for female response to mating call appeared statistically nonsignificant. However, appreciable "maternal genetic effects" suggest that maternal egg provisioning and other indirect maternal determinants of the embryonic environment significantly contributed to variation in male mating call and female response to mating calls. Thus, environmental factors can generate substantial variation in A. socius mating call, and, more importantly, their marginal effect on female responses to either fast-chirp or long-chirp mating calls suggest negative fitness consequences to males producing alternative types of calls. Future studies of sexual selection and SMRS evolution, particularly those focused on hybrid zone dynamics, should take explicit account of the loose concordance between signal producers and responders suggested by the current findings.

Diversifying the academic public health workforce: strategies to extend the discourse about limited racial and ethnic diversity in the public health academy.

While public health has gained increased attention and placement on the national health agenda, little progress has been made in achieving a critical mass of underrepresented minority (URM) academicians in the public health workforce. In 2008, a telephone-based qualitative assessment was conducted with URM faculty of schools of public health to discuss this issue. As a result, we present successful strategies that institutional leaders can employ to extend the discourse about addressing limited diversity in the public health academy.

Diagnosis of skin lesions by trainee surgeons: experience improves accuracy.

INTRODUCTION: Accurate clinical diagnosis depends on the reliable recognition of signs and symptoms. This expertise comes from experience in seeing patients which has been traditionally gained over a long training period. Shortened specialist training (Modernising Medical Careers) has led to a greater reliance on structured teaching and skills transfer programmes. The accuracy of clinical diagnosis and the rate at which diagnostic skills improve during training is important for the assessment of trainees, and the delivery of care. PATIENTS AND METHODS: This study assessed the accuracy of clinical diagnosis of skin lesions by two junior plastic surgery trainees. They were asked to diagnose 120 consecutive skin lesions seen in a pigmented skin lesion clinic in 2005, with the histological diagnosis being confirmed following subsequent excision. The process was repeated a year later in 2006 to enable the rate of correct diagnosis to be compared. RESULTS: Initially, 53.3% of diagnoses were correct. A year later, this had risen to 65.0%. Twenty-two different skin pathologies were present in excised specimens, and skin cancers comprised 30%. The trainees demonstrated 93.8% sensitivity in their initial diagnosis of malignancy (95% CI, 79.2-99.2) and 97.4% a year later (95% CI, 86.5-99.9). However, specificity was 69.3% (95% CI, 58.6-78.7) in 2005 and 71.6% (95% CI, 60.5-71.4) in 2006. CONCLUSIONS: Accuracy in the diagnosis of the wide range of skin conditions presenting to an out-patient clinic was shown to increase over a 1-year period. We feel that this improvement resulted from regular clinical exposure supported by a structured learning programme. The shortening of the specialist training period may affect the acquisition of diagnostic skills by trainees and impact on the confidence with which they commence consultant practice.

A lifelike patient simulator for teaching robotic colorectal surgery: how to acquire skills for robotic rectal dissection.

BACKGROUND: The use of robotic systems for colorectal resections is well documented, but robotic surgery is not yet established as a substitute for all laparoscopic colorectal procedures. The features of the new-generation robotic system seem to be well suited for proper mesorectal excision, with the identification and preservation of autonomic pelvic nerves. Proper training in the use of robotic skills is essential. METHODS: This report describes the creation of a pelvic model that can be used to teach the complex skills needed for successful completion of robotic rectal dissection. The model was designed to be cost effective, portable, and reusable in multiple teaching programs. Both the setup and size of the trainer were designed to be the same as those for a real patient and to allow for proper simulation of port placement in a true robotic rectal dissection. The operative field was molded directly onto a replica of a human skeleton, and the materials that make up the trainer closely replicate the consistency of a real patient. RESULTS: To date, no adequate artificial pelvic models have been available for rectal dissection. Cadaveric models are expensive, and virtual reality trainers, although offering an attractive alternative for some procedures, currently are not available for complex robotic tasks such as rectal dissection. One major advantage of this trainer is that it allows for the surgeon to develop proficiency in both the areas of robotic setup and console without the assistance of a second surgeon. CONCLUSIONS: The trainer described in this report provides an accurate simulation of true robotic rectal dissection. Its portability makes it easy to use at various hospitals. As robotic surgery becomes more common, this training tool has the potential to help surgeons quickly build the skills necessary for the successful use of robotic surgery in the area of rectal dissection.

Stratification of patients by melanoma cell adhesion molecule (MCAM) expression on the basis of risk: implications for sentinel lymph node biopsy.

BACKGROUND: The usual indication for sentinel lymph node biopsy (SLNB) in melanoma is a primary tumour >1mm thickness but under these criteria less than 20% of SLNBs are positive. Of those patients with a negative sentinel node (SN) over 10% will have disease recurrence within 3 years. A more accurate delineation of candidate patients for SLNB and risk profile for negative SN patients is therefore desirable. Melanoma cell adhesion molecule (MCAM) is a predominant cell adhesion molecule of melanomas and its expression has been implicated in tumour progression and metastasis. AIMS: To compare MCAM expression in primary and metastatic melanoma and to investigate if MCAM expression in patients meeting the criteria for SLNB correlated with patient outcome. METHODS: Tissue arrays of primary (n=78) and metastatic (n=92) melanomas were constructed from archived paraffin embedded tissue and MCAM expression detected by immunohistochemistry. Staining positivity and intensity were assessed by visual scoring and correlated with clinical outcome. RESULTS: In patients meeting the current criteria for SLNB, Cox multivariate analysis showed both MCAM expression positivity and intensity were independently predictive of survival (P=0.007) and development of lymph node disease (P=0.01) in primary melanoma over and above established markers of prognosis, such as Breslow thickness. MCAM-negative patients had a 5-year survival of 92% compared with 40% for MCAM positive. CONCLUSIONS: Measurement of MCAM expression represents a potential method to stratify SLNB patients on the basis of risk. This would have considerable benefits in terms of both cost and patient morbidity.

Ki-67 expression in melanoma. A potential method of risk assessment for the patient with a positive sentinel node.

Melanoma patients with a positive sentinel node biopsy generally proceed to regional lymph node dissection, though ultimately only around 20% have evidence of tumour in their "non-sentinel" nodes. A means to identify patients at high risk of non-sentinel node involvement could potentially spare a large number of patients a procedure with significant morbidity. The proliferation marker Ki-67 has been associated with tumour progression in primary melanoma but has not been extensively studied in metastases. The study aims to investigate Ki-67 in primary melanoma and lymph node metastases and investigate any relationship with disease progression. Tissue Arrays of primary melanoma (n=79) and lymph node metastases (n=92) were constructed from paraffin embedded tissue and Ki-67 expression examined by immunohistochemistry. Staining positivity and intensity were assessed and correlated with standard staging criteria and clinical outcome. High Ki-67 expression was associated with both Breslow thickness (chi(2)=8.54, p=0.035) and presence of ulceration (Fisher's Exact test p=0.003) in primary melanoma. In lymph node metastases high Ki-67 expression correlated with Nodal (N) Stage (chi(2)=8.193, p=0.0 17). High Ki-67 expression is associated with melanoma progression and multiple lymph node involvement. This might potentially form the basis of a risk analysis for patients with positive sentinel nodes.

Weaning from mechanical ventilation.

Weaning covers the entire process of liberating the patient from mechanical support and from the endotracheal tube. Many controversial questions remain concerning the best methods for conducting this process. An International Consensus Conference was held in April 2005 to provide recommendations regarding the management of this process. An 11-member international jury answered five pre-defined questions. 1) What is known about the epidemiology of weaning problems? 2) What is the pathophysiology of weaning failure? 3) What is the usual process of initial weaning from the ventilator? 4) Is there a role for different ventilator modes in more difficult weaning? 5) How should patients with prolonged weaning failure be managed? The main recommendations were as follows. 1) Patients should be categorised into three groups based on the difficulty and duration of the weaning process. 2) Weaning should be considered as early as possible. 3) A spontaneous breathing trial is the major diagnostic test to determine whether patients can be successfully extubated. 4) The initial trial should last 30 min and consist of either T-tube breathing or low levels of pressure support. 5) Pressure support or assist-control ventilation modes should be favoured in patients failing an initial trial/trials. 6) Noninvasive ventilation techniques should be considered in selected patients to shorten the duration of intubation but should not be routinely used as a tool for extubation failure.