Incompletely excised lentigo maligna melanoma is associated with unpredictable residual disease: clinical features and the emerging role of reflectance confocal microscopy.

BACKGROUND: Lentigo maligna/lentigo maligna melanoma (LM/LMM) poses a treatment and surgical challenge given unpredictable subclinical extension resulting in incomplete excision. OBJECTIVES: To describe the demographic, clinical and pathologic characteristics of incompletely excised LM/LMM. To evaluate the potential role of reflectance confocal microscopy (RCM). PATIENTS AND METHODS: A retrospective review of a melanoma database at a tertiary cancer centre for patients referred with 'incompletely excised LM/LMM' or 'incompletely excised melanoma' between October 2006 and July 2017. We recorded clinical and pathological data and surgical margins needed to clear the residual LM/LMM. The second part consisted of a prospective cohort of patients in which RCM was performed when presenting with incompletely excised LM/LMM. RESULTS: We included a total of 67 patients (retrospective + prospective cohort); mean age was 64.9 (standard deviation: 11.3) years and 52.2% were males. For the retrospective cohort (n = 53), the mean scar size was 3.4 cm. The average initial margins excised prior to presentation were 4.8 mm (range 3-7 mm). The average additional margin needed to clear the residual, incompletely excised LM/LMM was 7.8 mm. For the prospective cohort (n = 14), there were no differences in age, gender or size when compared to the retrospective cohort. RCM had a diagnostic accuracy of 78.6%, a sensitivity of 90.9%, a specificity of 33.3% and a positive predictive value of 83.3% for the detection of incompletely excised LM/LMM. CONCLUSIONS: Incompletely excised LM/LMM is a poorly characterized clinical-pathological scenario that may require considerable extra margins for microscopic clearance. RCM may emerge as a valuable tool for the evaluation of patients with incompletely excised LM/LMM.

Reflectance confocal microscopy and dermoscopy aid in evaluating repigmentation within or adjacent to lentigo maligna melanoma surgical scars.

BACKGROUND: Determining whether repigmentation within or adjacent to lentigo maligna or lentigo maligna melanoma (LM/LMM) scars represents recurrence of melanoma is challenging. The use of reflectance confocal microscopy (RCM) and dermoscopy may aid in differentiating true melanoma recurrence from other causes of repigmentation. OBJECTIVES: To describe the characteristics of repigmentation within or adjacent to LM/LMM scars observable on RCM and dermoscopy. METHODS: We retrospectively analysed patients who presented with new pigmentation within or adjacent to scars from surgically treated LM/LMM between January 2014 and December 2018. Clinical and demographic characteristics and time to recurrence were recorded. RCM was used to evaluate areas of pigmentation before biopsy. If available, dermoscopic images were also evaluated. RESULTS: In total, 30 confocal studies in 29 patients were included in the study cohort. Twenty-one patients had biopsy-confirmed recurrent LM/LMM; the remainder had pigmented actinic keratosis (n = 4) or hyperpigmentation/solar lentigo (n = 5). RCM had sensitivity of 95.24% (95% CI, 76.18-99.88%), specificity of 77.7% (95% CI, 39.99-97.19%), positive predictive value of 90.91% (95% CI, 74.58-97.15%) and negative predictive value of 87.5% (95% CI, 50.04-98.0%). The most common dermoscopic feature observed among patients with recurrent LM/LMM was focal homogeneous or structureless areas of light-brown pigmentation (92.8% vs. 37.5% in patients with other diagnoses; P = 0.009). LM-specific dermoscopic criteria were present in only 28.5% of patients with recurrent LM/LMM. CONCLUSIONS: Reflectance confocal microscopy and dermoscopy are valuable tools for the comprehensive evaluation of repigmentation within or adjacent to LM scars.

The effect of acute exercise on the performance of verbal fluency in adolescents and young adults with Down syndrome: a pilot study.

BACKGROUND: The high prevalence of cognitive dysfunction is well documented in individuals with Down syndrome. However, only a few studies have focused on the effect of exercise on cognitive performance in this population. In particular, verbal fluency has been shown to be relevant to the early onset of Alzheimer's disease in individuals with Down syndrome. Thus, this study was aimed at investigating the relationship between acute exercise and verbal fluency in this population. METHODS: It was a pre-post design. Twenty-eight participants (aged 14-31) were assigned to high-intensity exercise (i.e. 70-85% of predicted maximum heart rate) (N = 8), moderate-intensity exercise (i.e. 50-69% of predicted maximum heart rate) (N = 10) or attentional control (N = 10) groups. Two exercise groups walked on a treadmill using an incremental walking protocol, and the attentional control group watched a video for 20 min. Measures of verbal fluency (i.e. semantic fluency and phonetic fluency) were tested pre-intervention and post-intervention. RESULTS: The result showed a quadric trend between semantic fluency and intensity of exercise. The improvement in cognitive performance on semantic fluency test was observed in the moderate-intensity exercise. However, neither a linear trend nor a quadric trend was seen in phonetic fluency. CONCLUSIONS: The result showed an inverted-U relationship between exercise intensity and semantic fluency. A larger sample size, testing time and more reliable psychophysiological measures (e.g. VO2 max and neuroimaging technology), should be considered to explore the underlying mechanisms in this population.

Walking performance in adolescents and young adults with Down syndrome: the role of obesity and sleep problems.

BACKGROUND: High prevalence of obesity and features of obstructive sleep apnea (OSA) are major health issues in individuals with Down syndrome (DS), and both may also affect adversely on their daily activities. Further, lower levels of physical work capacity (PWC) have been reported in this population compared to their peers with intellectual disabilities. However, no study examines the relationships between obesity and sleep problems with PWC in individuals with DS. Thus, this study investigated the influence of body mass index (BMI) and different types of sleep problems on PWC in adolescents and young adults with DS (14-31 years). METHODS: The incremental treadmill walking trial was used to assess PWC. RESULTS: The negative associations were indicated between BMI and walking steps (p = .03) as well as features with OSA and walking steps (p = .04). Thus, BMI and OSA were included in the regression analysis to estimate the walking steps achieved during walking trials. In addition, Bland-Altman plots demonstrated no overestimation and underestimation of variability in the difference between actual and estimated walking steps developed by using BMI and OSA. CONCLUSIONS: Obesity and sleep problem are potentially detrimental to walking performance (i.e., fewer walking steps) in individuals with DS. Thus, individuals with DS may adopt a slow walk speed due to the increased balance deficits and physical fatigue that result from obesity and sleep fragmentation, respectively. Exercise interventions, which have the potential to reduce obesity and OSA, are recommended to improve the accomplishment of PWC in individuals with DS.

Dose-response relationship between intensity of exercise and cognitive performance in individuals with Down syndrome: a preliminary study.

BACKGROUND: Cognitive performance has been shown to be relevant to the early onset of Alzheimer's disease in individuals with Down syndrome. This study was aimed at investigating the dose-response relationship between acute exercise intensity and cognitive performance in this population. METHODS: In the current study, we measured information processing speed and two aspects of executive function (i.e. attention shifting and inhibitory control). Participants were assigned to high-intensity exercise (i.e. 75-85% of predicted maximum heart rate) (N = 6), moderate-intensity exercise (i.e. 50-75% of predicted maximum heart rate) (N = 6) or attentional control (N = 6) groups. Two exercise groups walked on a treadmill using an incremental intensity walking protocol, and the attentional control group watched a video for 20 min. Measures of information processing speed and executive function were tested pre-intervention and post-intervention. RESULTS: Our results indicated that the performance in choice reaction time test was impaired in the high-intensity exercise, whereas improved performance was observed in the moderate-intensity exercise. However, moderate-intensity and high-intensity exercises were beneficial for inhibitory control aspect of executive function. Further, inconsistent with previous studies, a quadric trend was seen in information processing speed, and a liner trend was evident in inhibitory control. CONCLUSIONS: Future research is needed to examine with a larger sample size, and more physiological measures are necessary to explore the underlying mechanisms in the relationship between exercise intensity and cognitive performance in individuals with Down syndrome.

The association between a single bout of moderate physical activity and executive function in young adults with Down syndrome: a preliminary study.

BACKGROUND: This study was aimed at investigating the impact of a single exercise intervention on executive function in young adults with Down syndrome (DS). METHODS: Considering the relations among executive function, physical and mental health and early onset of Alzheimer's disease in this population, we tested three components of executive function (e.g. choice-response time, attention shifting and inhibition) that have been shown to be impaired in previous studies. Ten persons with DS were assigned to an exercise group, who walked on a treadmill for 20 min at moderate intensity and ten additional persons with DS were assigned to an attentional control group, who watched a video. Measures of executive function were tested pre and post interventions. RESULTS: These results showed non-significant improvements in choice-response time (P = 0.32) and attention shifting (P = 0.13) but a statistically significant improvement in inhibition (P = 0.03) after the exercise intervention. CONCLUSIONS: Given the improved inhibition ability, exercise may be an effective intervention, even in a signal session. However, only a few studies have focused on this topic. Based on theoretical models linking exercise to executive function, we proposed that exercise may increase arousal status or enhance neural transmission. Hence, future work is needed to examine the exact mechanism in the relationship between exercise and executive function for individuals with DS.

Assisted cycling exercise improves fine manual dexterity in persons with Down's syndrome.

BACKGROUND: This study was aimed at investigating the impact of assisted cycling therapy (ACT) on fine manual dexterity in adults with Down's syndrome (DS). METHODS: Nine persons with DS completed four different interventions: voluntary exercise (VE), voluntary with music (VEM), assisted exercise (AE) and no exercise (NE). Fine manual dexterity (e.g., Purdue Pegboard) was tested pre and post interventions. RESULTS: The results showed dominant and bimanual hands were improved after AE but no evident in either subtest after VE. The assembly subtest, processed by spatial-temporal ability, was only improved after VEM and NE. CONCLUSIONS: It is speculated that AE stimulated more peripheral sensory input to the motor cortex and neurotransmitters than the other interventions. In addition, the involvement of music may enhance spatial intelligence during VEM. Even though the exact mechanisms are still unknown, the implication of our results showed that AE and VEM can improve fine manual dexterity in persons with DS.

Treadmill walking effects on grip strength in young men with Down syndrome.

This study was aimed at investigating the relation between grip strength and anthropometric factors and the impact of an aerobic exercise on grip strength in young men with Down syndrome (DS). This study was a pre-post design. Twelve males with DS were assigned to an exercise group, who walked using an incremental protocol on a treadmill for 20 min at aerobic levels. Eight additional persons with DS were assigned to an attentional control group, who watched a video. Measure of grip strength was tested pre- and post-interventions. The results showed positively significant relationship among grip strength and age (r=.74, p<.01), weight (r=.52, p=.02), body mass index (r=.61, p=.01) and waist circumference (r=.54, p=.02). In addition, Grip strength was slightly improved after exercise (p=.03) but decreased after control condition. The results showed that anthropometric factors, such as age, weight, body mass index and waist circumference, were positively correlated with grip strength in young men with DS. Further, improvement in grip strength can be found even after a single exercise session. This finding emphasizes the importance of maintaining an active lifestyle in persons with DS for performing activities of daily living.

The impact of sleep disruption on executive function in Down syndrome.

The high prevalence of sleep disorders, particularly obstructive sleep apnea, is well established in children with Down syndrome. However, only a few studies have focused on older children and young adults in this population. Given the presence of sleep disorders and the early emergence of Alzheimer's disease, more work is needed to examine the relationship between sleep and cognition in Down syndrome. Twenty-nine adolescents and young adults with Down syndrome participated in the present study. Parents reported on their sleep difficulties using a well-validated measure of sleep problems in intellectual disabilities. Based on theoretical models linking obstructive sleep apnea to prefrontal cortex dysfunction, we tested components of executive functions that have been shown to be impaired in previous studies of Down syndrome. First, results indicate that participants with Down syndrome with higher body mass index also had increased caregiver reports of sleep apnea symptoms. Individuals with high ratings of sleep disruption also showed greater difficulties with executive function. These results suggest that sleep disruption may place this set of functions at risk in young adults. Future work should examine if this risk may result in earlier onset of dementia or steeper decline with Alzheimer's disease. Further, additional studies are needed to investigate the effect of exercise interventions and weight reduction on sleep disorders in this population.