Treatment outcomes in mild traumatic brain injury: a systematic review of randomized controlled trials.

OBJECTIVES: Mild traumatic brain injury (mTBI) is a controversial and under-researched area, despite most traumatic brain injuries being classed as mild. Our objective was to review the evidence underpinning these approaches to treat mTBI including educational, psychological, rehabilitative and pharmacological approaches and discuss their efficacy. METHODS: A systematic review of literature was carried out using Web of science, Scopus, Medline, Pubmed, Cinahl, and PsychInfo databases. Randomized Controlled Trials (RCTs) looking at treatment outcome in mTBI for adults were included, published between 1980 and 2019. Methodological quality of the studies was reviewed using the Scottish Intercollegiate Guideline Network (SIGN) checklist for RCTs. RESULTS: Searches identified 3993 studies, of which 25 met inclusion criteria, and a total number of participants of 3213. Mean age was 35, and 59% male. Ten studies had <100 participants, 15 studies 100-395. Studies were grouped into education and early intervention, rehabilitation (8), psychological interventions (4), and pharmacotherapy (4). Inconsistency of definitions and outcome measures used precluded meta-analysis. CONCLUSIONS: Traditional education and reassurance can no longer be recommended as having the best evidence base for efficacy as compared to psychological and rehabilitative approaches, and guidelines should begin to reflect this.

A spray containing extracts of oat plantlets and Uncaria tomentosa relieves pain associated with chronic inflammatory skin diseases and dermatological procedures.

BACKGROUND: Inflammation from skin conditions such as psoriasis, eczema-like atopic dermatitis (AD) and hand eczema (HE) and following dermatological procedures (post-acts) can result in intense itching and cutaneous pain. Dermo-cosmetics containing plant extracts have been shown to reduce or alleviate these symptoms. OBJECTIVES: Assessment of the tolerability and efficacy of a spray containing Rhealba\xAE Oat plantlets and Uncaria tomentosa extracts in adults and children with inflammatory skin diseases and after dermatological procedures. METHODS: Data from five open label studies were analysed (Study 1: adults with AD; Study 2: children with AD; Study 3: adults with psoriasis; Study 4: adults with HE; Study 5: adults who had undergone a dermatological procedure: laser, intense pulsed light, glycolic acid peeling, photodynamic therapy or cryotherapy procedure). In all studies, subjects could use the test product up to six times per day for symptom relief. Physical and functional signs of inflammation, treatment-emergent adverse events (TEAEs), soothing effect, changes in quality of life, cutaneous pain and cosmetic acceptability were compared pre- and postapplication. RESULTS: A total of 176 subjects were enrolled across the five studies. Overall, investigators judged the dermatological tolerance of the test product containing Rhealba\xAE Oat plantlets extract and Uncaria tomentosa as good to excellent. All studies showed significant improvements in physical signs, reduction in itching and feeling of pain (P < 0.05). The soothing effect was evident after the first application. TEAEs were mostly mild, transient and occurred within the first few days of treatment. The majority of subjects reported improved QoL across the studies. CONCLUSIONS: The dermo-cosmetic spray containing Rhealba\xAE Oat plantlets extract and U. tomentosa was well tolerated and efficacious in providing relief of symptoms associated with cutaneous pain from inflammatory skin diseases and following dermatological procedures; however, further studies are needed to rule out alternative explanations of symptom reduction such as natural history and response biases.

Dermoscopy vs. reflectance confocal microscopy for the diagnosis of lentigo maligna.

BACKGROUND: Several dermoscopic and in vivo reflectance confocal microscopy (RCM) diagnostic criteria of lentigo maligna (LM)/lentigo maligna melanoma (LMM) have been identified. However, no study compared the diagnostic accuracy of these techniques. OBJECTIVE: We evaluated the diagnostic accuracy of dermoscopy and RCM for LM/LMM using a holistic assessment of the images. METHODS: A total of 223 facial lesions were evaluated by 21 experts. Diagnostic accuracy of the clinical, dermoscopic and RCM examination was compared. Interinvestigator variability and confidence level in the diagnosis were also evaluated. RESULTS: Overall diagnostic accuracy of the two imaging techniques was good (area under the curve of the sROC function: 0.89). RCM was more sensitive (80%, vs. 61%) and less specific (81% vs. 92%) than dermoscopy for LM/LMM. In particular, RCM showed a higher sensitivity for hypomelanotic and recurrent LM/LMM. RCM had a higher interinvestigator agreement and a higher confidence level in the diagnosis than dermoscopy. CONCLUSION: Reflectance confocal microscopy and dermoscopy are both useful techniques for the diagnosis of facial lesions and in particular LM/LMM. RCM is particularly suitable for the identification of hypomelanotic and recurrent LM/LMM.

NF-kB2 induces senescence bypass in melanoma via a direct transcriptional activation of EZH2.

Enhancer of Zeste homologue 2 (EZH2) belongs to the polycomb repressive complex 2 and catalyzes the methylation of histone H3 lysine 27. These pivotal epigenetic marks are altered in many cancers, including melanoma, as a result of EZH2 overexpression. Here, we show that the non-canonical-NF-kB pathway accounts for most of the NF-kB activity in melanoma cells, in contrast to non-cancer cells. We identify the non-canonical-NF-kB pathway as a key regulator of EZH2 expression in melanoma. We show a striking correlation between NF-kB2 and EZH2 expression in human melanoma metastases. We demonstrate that inhibition of the non-canonical NF-kB pathway by targeting NF-kB2/p52 or the upstream kinase NIK restores the senescence program in melanoma cells through the decrease of EZH2. On the contrary, the overexpression of NF-kB2/p52 in normal human melanocytes prevents stress- and oncogene-induced senescence. Finally, we show in mouse models that the inhibition of the non-canonical NF-kB pathway restores senescence and induces a dramatic reduction in tumor growth compared with controls, thus providing potential drug targets for the re-induction of senescence in melanoma and other cancers where EZH2 is overexpressed.

Reflectance confocal microscopy for the diagnosis of vulvar naevi: six cases.

BACKGROUND AND OBJECTIVES: The differential diagnosis between vulvar naevi and melanoma is challenging. In vivo reflectance-mode confocal microscopy (RCM) is an emerging technique that allows non-invasive high-resolution imaging of the skin and mucosa. It has recently been used for the study of vulvar melanosis and melanoma, but it has not been so far employed for the diagnosis of genital naevi. The objective of this study is to evaluate RCM features of vulvar naevi and to compare them with dermoscopical and histopathological aspects. METHODS: Clinical, dermoscopical, in vivo RCM and histological features of six vulvar naevi were evaluated. RESULTS: The clinical and/or dermoscopical aspects were suspicious in all six cases. RCM showed a blue naevus, an atypical genital naevus, a junctional naevus and three compound naevi that were later confirmed by histological examination. In one compound naevus, RCM showed focal cytological atypia and architectural irregularity without clear features of malignancy, confirmed by histological examination. CONCLUSIONS: Reflectance-mode confocal microscopy can play a role in non-invasive diagnosis of vulvar naevi, but further broader studies are required to validate our observations.

Reflectance confocal microscopy features of acral lentiginous melanoma: a comparative study with acral nevi.

BACKGROUND: Acral lentiginous melanoma (ALM) can be difficult to differentiate from acral nevus. Reflectance confocal microscopy (RCM) is widely used for the diagnosis of melanocytic tumours, but the RCM features of ALM and acral nevus have not been described yet. OBJECTIVE: To determine the RCM features of ALM and acral nevus, and their correlation with clinical and histological characteristics. METHODS: Retrospective study of 17 cases of ALM and 26 acral nevi. RESULTS: Pagetoid cells were present in all ALMs with a visible epidermis and in three nevi. A proliferation of atypical melanocytes at the dermal-epidermal junction (DEJ) and/or in the dermis was visible in nine ALMs but not in nevi. The histopathological examination of initial skin biopsies was unable to diagnose ALM in four cases, differing from RCM that could identify malignant tumour cells by exploring the whole lesions. CONCLUSION: Reflectance confocal microscopy can help in the differentiation of ALM and acral nevus, and to guide the biopsy.