Improving the early diagnosis of early nodular melanoma: can we do better?

Introduction: Cutaneous melanoma is the sixth most common malignant cancer in the USA. Among different subtypes of melanoma, nodular melanoma (NM) accounts about 14% of all cases but is responsible for more than 40% of melanoma deaths. Early diagnosis is the best method to improve melanoma prognosis. Unfortunately, early diagnosis of NM is particularly challenging given that patients often lack identifiable risk factors such as many moles or freckles. Moreover, early NM may mimic a range of benign skin lesions that are not routinely excised or biopsied in every day practice. For this reason, specific clinical and skin imaging clues have been proposed to improve early detection of NM.Areas covered: The review discusses about the noninvasive tools to diagnose thin melanoma, particularly NM. Expert commentary: Currently, dermatologists present a wide opportunity of diagnostic tools. Current data suggest that the early diagnosis of NM is a major challenge as the majority of early NM are symmetric, roundish, and lack specific pattern. Another promising strategy is based on recent data suggesting that artificial intelligence based on deep convolutional neural networking is able to outperform average dermatologist. Further research is necessary to validate the performance of this method in the real world and in the clinical setting

High dose gonadotropin stimulation increases endometrial thickness but this gonadotropin induced thickening does not have an effect on implantation.

INTRODUCTION Endometrial thickness <8mm is related with lower pregnancy rates. This raises the question if endometrial thickness can be increased by gonadotropin stimulation to increase estradiol (E2) concentration and if such an artificial thickening of the endometrium has an effect on implantation. A model to address this question is the comparison of endometrial thickness and outcome parameters in conventional gonadotropin stimulated IVF (cIVF) compared to unstimulated natural cycle IVF (NC-IVF). MATERIAL AND METHODS Retrospective study including 235 cIVF and 616 NC-IVF cycles without embryo selection and with fresh transfer on day 2 and 3 from 2015 to 2019. Endometrial and E2 measurements were included and analysed between day -4 and -2 (0 = day of aspiration). The effects of E2 on endometrial thickness, endometrial growth and the effect of endometrial thickness on implantation rates and live births were analysed. RESULTS Endometrial thickness was found to be higher in cIVF compared to NC-IVF (p < 0.001). On day -2, the day when ovulation was triggered, mean endometrial thickness was 9.75 ± 2.05mm and 8.12 ± 1.66mm, respectively. The increase in endometrial thickness slowed down with increasing E2 concentrations (time x estradiol concentration: -0.19, p = 0.010). Implantation rates were not significantly different in cIVF and NC-IVF cycles (clinical pregnancy rate: 19.1% vs. 15.4% p = 0.2; live birth rate: 12.8% vs. 11.7%, p = 0.8). CONCLUSIONS Endometrial growth dynamic is different and endometrium is thicker in cIVF compared to NC-IVF. Pregnancy and live birth rates are not different. Gonadotropin induced thickening of the endometrium does not appear to improve implantation

Optimal Timing of Ovulation Triggering to Achieve Highest Success Rates in Natural Cycles-An Analysis Based on Follicle Size and Oestradiol Concentration in Natural Cycle IVF.

Introduction Timing of ovulation triggering is essential in infertility treatments including treatments based on natural menstrual cycles. However, data on follicle size and oestradiol (E2) concentration are limited. Therefore, the model of natural cycle IVF (NC-IVF) was applied to provide more detailed information on these parameters to better schedule the optimal time for triggering ovulation. Materials and Methods A retrospective cross-sectional analysis of 606 monofollicular NC-IVF cycles was performed at a university-based IVF centre from 2016 to 2019. Follicle size and E2 and LH serum concentrations were evaluated on day -5 to 0 (day 0 = day of oocyte retrieval). Ovulation was triggered if follicle size was 14-22 mm. Patients with irregular cycles, endometriosis >II°, cycles with azoospermia or cryptozoospermia and cycles with inconsistent data were excluded. All parameters were analysed inter- and intraindividually, and associations of the parameters were evaluated. Associations were adjusted for age, cause of infertility and number of previous transfers. Results The mean age of women undergoing NC-IVF was 35.8 ± 4.0 years. Follicle size increased by 1.04 ± 0.03 mm, and E2 concentration by 167 ± 11.0 pmol/l per day.Based on a multivariate adjusted mixed model with follicle size, E2 and their interaction, the number of retrieved oocytes was associated with E2 concentration (aOR 1.91, 95% CI: 1.03-3.56; p = 0.040). Maturity of oocytes was associated not only with E2 concentration (aOR 2.01, 95% CI: 1.17-3.45; p = 0.011) but also with follicle size (aOR 1.27, 95% CI: 1.01-1.60; p = 0.039), as was the interaction of both parameters (aOR 0.96, 95% CI: 0.93-0.99; p = 0.017).LH surge was calculated to start in 25% of cases at an E2 level of 637 pmol/l, in 50% of cases at 911 pmol/l and in 75% of cases at an E2 level of 1,480 pmol/l.The live birth rate per follicle aspiration cycle was (non-significantly) higher in cycles with follicles sizes at the time of oocyte retrieval of 18-22 mm (7.7%-12.5%) versus in cycles with follicles sizes of 14-17 mm (1.6%-4.3%). Conclusion The study contributes to an optimization of infertility treatments involving natural cycles. The study gives guidance about the number of days required after follicle monitoring to schedule the optimal time for triggering ovulation

Integrating the concept of field cancerization in the classification and risk assessment of cutaneous squamous cell carcinoma: proposal for a new classification and terminology of keratinocyte skin cancer.

The term keratinocyte skin cancer (KC) stands as an umbrella for different stages within the progression of cutaneous squamous cell carcinoma (cSCC). 1\u20102 Its earliest form is named actinic keratosis (AK), while for the in\u2010situ form different synonyms, namely intraepidermal carcinoma (IEC), Bowen's Diseases (BD) and cutaneous squamous cell carcinoma in situ [cSCC(Tis)] or intraepithelial squamous cell carcinoma (iSCC) are used.3 Instead, cSCC is histopathologically classified into well, moderately and poorly differentiated subtypes

Oocyte maturity, oocyte fertilization and cleavage-stage embryo morphology are better in natural compared with high-dose gonadotrophin stimulated IVF cycles.

RESEARCH QUESTION Does high-dose gonadotrophin stimulation have an effect on oocyte and early-stage embryo development? DESIGN This was a retrospective study including 616 natural cycle IVF (NC-IVF) and 167 conventional IVF (cIVF) cycles. In total, 2110 oocytes were retrieved and analysed in fresh cycles. In NC-IVF, only human chorionic gonadotrophin was applied to trigger ovulation. In cIVF, antagonist protocols with daily 150-300 IU of human menopausal gonadotrophins were performed. The effect of gonadotrophins on oocyte and early-stage embryo development was analysed. Primary outcomes were the occurrence of mature (metaphase II) oocytes, zygotes and embryos with good morphology at the cleavage stage 2 days after oocyte retrieval. RESULTS The mature oocyte rate (number of mature oocytes/number of retrieved oocytes) was higher in NC-IVF than cIVF cycles (89% versus 82%, adjusted odds ratio [aOR] 1.79, P = 0.001), as was the zygote rate per oocyte retrieved (70% versus 58%, aOR 1.76, P = 0.001) and the zygote rate per mature oocyte (79% versus 71%, aOR 1.62, P = 0.001). The percentage of zygotes that developed into cleavage-stage embryos was no different. For the transferred embryos, the probability of having a good embryo morphology with four blastomeres and a fragmentation of <10% (score 0) in cleavage-stage embryos was found to be higher in NC-IVF (proportional aOR for four blastomeres 2.00, P < 0.001; aOR 1.87 for a fragmentation score of 0, P = 0.003). CONCLUSIONS Oocyte maturity, oocyte fertilization and morphology of the cleavage-stage embryo are affected by high-dose gonadotrophin stimulation in fresh IVF cycles

Efeitos maternos e perinatais com utilização de floral no trabalho de parto: ensaio clínico randomizado

Objetivo: Avaliar os efeitos clínicos, obstétricos maternos e perinatais com o uso de essências florais no trabalho de parto, frente a fatores que o potencializam.Método: Ensaio clínico, randomizado, controlado, em 164 parturientes divididas em dois grupos, essências florais e placebo, respectivamente, avaliadas pré e pós intervenção. Realizado em centro de parto normal, na cidade de São Paulo, de maio a outubro de 2018. Os dados foram analisados por estatística descritiva, teste t de Student hipótese bilateral, t crítico observado negativo e positivo, Qui-quadrado de Pearson, Exato de Fisher.Resultados: Observou-se no Grupo Experimental, moderada elevação da pressão arterial sistólica (p=0,046) da frequência (p=0,055) e intensidade das contrações (p=0,031), assim como, redução do tempo ao nascimento (194 minutos), maior número de partos vaginais (p=0,038) e melhor padrão de vitalidade fetal.Conclusão: Evidenciou-se ação positiva da Essência Floral perante os fatores potencializadores do trabalho de parto, sendo efetiva nas repercussões clínicas e obstétricas maternas, bem como perinatais. Palavras-chave: Trabalho de parto. Terapias complementares. Essências florais. Ensaio clínico

Breast Cancer-Related Neoplastic Alopecia: A Case Report and Review of the Literature

Neoplastic alopecia (NA) is defined as an organized hair loss in single or multiple areas of the scalp caused by a primary tumor that has metastasized to the skin of the scalp. Due to its localization and clinical appearance, NA should be placed in differential diagnosis with alopecia areata or other entities. To date, pathognomonic dermoscopic criteria of NA have not yet been described: the absence of classical criteria of other scalp diseases in addition to a major neovascularization with on-focus arborizing vessels and erosions or ulcerations may help the clinician to suspect a diagnosis of secondary alopecia. Dermatologists should pay more attention to these rare forms of secondarism because in exceptional cases, a simple alopecia of the scalp can hide a new, relapsing or metastatic neoplasia

Pattern of response of unresectable and metastatic cutaneous squamous cell carcinoma to programmed death-1 inhibitors: A review of the literature

Cutaneous squamous cell carcinoma (cSCC) is the second most frequent nonmelanoma skin cancer (NMSC). The majority of in situ cSCC [cSCC (Tis)] can be cured surgically, while local advanced and metastatic ones require other treatments, but there are no therapies approved by U.S. Food and Drug Administration (FDA). Available treatments for these stages included radiotherapy, chemotherapy as cisplatin, but responses to these treatments are usually of short duration. Programmed death-1 (PD-1) inhibitors (pembrolizumab, nivolumab, and cemiplimab) are an innovative immunologic treatment that now has been shown to be useful for the treatment of advanced cSCC. Nowadays, data about the response rate with the use of PD-1 inhibitors in cSCC are still few and, especially, the duration of the response after the start of treatment is short. Moreover, the number of cases is too small to express the beneficial effects of these treatments, although most data reported in the literature show quite good response rates. This review focused on some of the studies and associated results through an interesting research on search engines of all the cases about these systemic drugs, analyzing effects and side effects, and the research has been conducted considering published cases since March 2016 to October 2019

Tissue Necrosis in Equine Associated with use of Phenylbutazone

Background: Wounds that occur with tissue necrosis and that result from the application of medications through the most diverse accesses are described as drug skin medical embolism or Nicholas syndrome in human medicine, with wide description. In veterinary medicine, this subject has not yet been described extensively and specifically in veterinary medicine, especially regarding to wounds that occurred after the application of non-intravenous medications in horses, even though these lesions are recurrent in the clinical routine.  This report aims to describe a case of skin necrosis in a horse, due to phenylbutazone infection. Case: A 7 year-old Mangalarga Marchador horse, weighing 400 kg, was admitted to the Veterinary Hospital for Large Animals of the Universiade Federal Rural do Rio de Janeiro (UFRRJ), with a history of phenylbutazone injection to the left side of the neck. The animal had an extensive wound on the neck and face on the left side and was characterized by the presence of cold and devitalized skin, with a hardened and parched appearance and that easily detached.  During the anamnesis, a single administration of 10 mL of a non-steroidal anti-inflammatory drug based on phenylbutazone was reported intramuscularly for about 10 days to control the pain resulting from the claudication present for 14 days. The medication was administered in the region of the lateral border of the neck, on the left side. After drug administration, the animal presented an increase in volume at the application site. After 24 h, the lesion spread from the inoculation region, extending to the head and chest of the animal. During debridement, it was found that the lesion did not reach the underlying muscle tissue. In addition to the wound, the animal had upper eyelid palsy, lower lip, and auricular ptosis. Treatment with surgical debridement of devitalized tissue, topical application of ozonated sunflower oil, ketanserin, and a free skin graft was instituted. During hospitalization, the animal had a corneal ulcer in the left eye with an unfavorable prognosis due to paralysis of the upper eyelid, with enucleation of the affected eyeball. The animal was under veterinary care for 180 days and was discharged when his wound was already in an advanced stage of healing. Discussion: The history of the application of phenylbutazone intramuscularly and the location and characteristics of the lesion presented by the patient in the present report suggest that this animal presented aseptic tissue necrosis resulting from the administration of non-steroidal anti-inflammatory drugs, phenylbutazone. Although aseptic tissue necrosis, better known as Nicolau's syndrome or drug embolism cutis, is widely characterized and described in this species, there are studies in the literature that reproduce the syndrome in pigs and rabbits. Phenylbutazone was able to cause arterial damage, mainly in the tunica intima of the artery in which the medication was administered, with perivascular inflammatory infiltrate and subsequent skin necrosis at the site of administration. In addition to the skin lesion, the animal started to show signs compatible with the left facial nerve lesion, evidenced by the immobility of the upper eyelid and labial and ear ptosis. This resulted in corneal ulceration and subsequent enucleation. The animal also developed chewing difficulty in the first months of hospitalization. This dysfunction may be due to a lesion of the mandibular nerve, responsible for innervating the masticatory muscles and the oral mucosa. However, the animal showed improvement in this aspect, no longer showing this condition after 90 days of hospitalization.  The treatment used was successful in healing the wound. Keywords: wound, tissue necrosis, iatrogenic injury, Nicolau Syndrome, treatment, horse. Título: Necrose tissular em equino associada ao uso de fenilbutazona. Descritores: ferida, necrose tecidual, iatrogenia medicamentosa, síndrome de Nicolau, tratamento, cavalo