Nodular type but not vitamin D levels increases the risk of second primary cancers in melanoma patients: An observational study of 663 patients / El melanoma de tipo nodular pero no los niveles de vitamina D aumenta el riesgo de desarrollar una segunda neoplasia no cutánea en pacientes con un melanoma: estudio observacional de 663 pacientes

Background Vitamin D deficiency associates with the risk of developing many diseases, including cancer. At the molecular level, vitamin D appears to have an antineoplastic effect. However, the role of vitamin D deficiency in cancer pathogenesis remains unelucidated and numerous studies have resulted in discordant results. This study aimed to determine whether vitamin D deficiency during melanoma diagnosis increases the risk of developing non-cutaneous second primary cancers (SPC). Materials and methods A retrospective study on 663 patients diagnosed with melanoma between 1 January 2011 and 31 October 2022. The effect of each variable on the development of a subsequent non-cutaneous cancer was performed using Kaplan–Meier curves and differences were assessed by log-rank tests. Cox proportional hazard univariate and multivariate models were used to quantify the effect of each variable in the time to develop a non-cutaneous neoplasia. Results Out of 663 patients, 34 developed a non-cutaneous SPC. There was no statistically significant association between vitamin D levels and non-cutaneous SPC development (log-rank, p=0.761). Age>60 years, stage III/IV, and nodular melanoma subtype were significantly associated with the development of a SPC. After multivariate analysis, only age>60 years (HR 3.4; HR CI 95%: 1.5–7.6) and nodular melanoma subtype (HR 2.2; HR CI 95%: 1.0–4.8) were included in the final model. Conclusions Our results suggest that vitamin D deficiency is not associated with an increased risk of developing non-cutaneous SPC in melanoma patients. However, age over 60 years and nodular melanoma subtype increase the risk for non-cutaneous SPC development (AU)

Antecedentes El déficit de vitamina D se asocia con un mayor riesgo de padecer varias enfermedades, incluido el cáncer. Molecularmente, esta parece tener un efecto antineoplásico. Sin embargo, el papel que juega en la patogénesis del cáncer no está bien esclarecido y hay resultados dispares en los estudios publicados. El objetivo del presente fue determinar si unos niveles de vitamina D deficientes en el momento del diagnóstico del melanoma aumentaba el riesgo de desarrollar un cáncer no cutáneo (CNC). Material y método Se diseñó un estudio retrospectivo de 663 pacientes diagnosticados de melanoma entre el 1 de enero de 2011 y el 31 de octubre de 2022. El efecto de cada una de las variables seleccionadas en el desarrollo de un CNC durante el seguimiento tras el diagnóstico del melanoma se realizó mediante el estudio de supervivencia con el método de Kaplan-Meier y las diferencias se evaluaron con la prueba de los rangos logarítmicos. Se elaboraron modelos uni y multivariados de riesgos proporcionales de Cox para cuantificar el efecto de cada valor de las variables de estudio en el tiempo para desarrollar un CNC. Resultados De los 663 pacientes, 34 desarrollaron un CNC tras el melanoma. No hubo diferencias estadísticamente significativas entre los grupos definidos por los niveles de vitamina D (log-rank, p = 0,761). Sin embargo, una edad > 60, el estadio III/IV, y el tipo nodular se asociaron significativamente al desarrollo de un CNC. Tras el análisis multivariado, solo la edad > 60 (hazard ratio [HR] 3,4; intervalo de confianza [IC] 95% HR:1,5-7,6) y el subtipo nodular de melanoma (HR 2,2; IC 95% HR:1,0-4,8) se mantuvieron en el modelo predictivo final. Conclusiones Nuestros resultados sugieren que unos niveles de vitamina D deficientes en el diagnóstico de melanoma no se asocian a un mayor riesgo de desarrollar un CNC. Sin embargo, en una edad > 60 y el subtipo nodular sí que aumentan el riesgo de desarrollar un CNC (AU)

[Artículo traducido] El melanoma de tipo nodular pero no los niveles de vitamina D aumenta el riesgo de desarrollar una segunda neoplasia no cutánea en pacientes con un melanoma: estudio observacional de 663 pacientes / Nodular Type but Not Vitamin D Levels Increases the Risk of Second Primary Cancers in Melanoma Patients: An Observational Study of 663 Patients

Antecedentes El déficit de vitamina D se asocia con un mayor riesgo de padecer varias enfermedades, incluido el cáncer. Molecularmente, esta parece tener un efecto antineoplásico. Sin embargo, el papel que juega en la patogénesis del cáncer no está bien esclarecido y hay resultados dispares en los estudios publicados. El objetivo del presente fue determinar si unos niveles de vitamina D deficientes en el momento del diagnóstico del melanoma aumentaba el riesgo de desarrollar un cáncer no cutáneo (CNC). Material y método Se diseñó un estudio retrospectivo de 663 pacientes diagnosticados de melanoma entre el 1 de enero de 2011 y el 31 de octubre de 2022. El efecto de cada una de las variables seleccionadas en el desarrollo de un CNC durante el seguimiento tras el diagnóstico del melanoma se realizó mediante el estudio de supervivencia con el método de Kaplan-Meier y las diferencias se evaluaron con la prueba de los rangos logarítmicos. Se elaboraron modelos uni y multivariados de riesgos proporcionales de Cox para cuantificar el efecto de cada valor de las variables de estudio en el tiempo para desarrollar un CNC. Resultados De los 663 pacientes, 34 desarrollaron un CNC tras el melanoma. No hubo diferencias estadísticamente significativas entre los grupos definidos por los niveles de vitamina D (log-rank, p = 0,761). Sin embargo, una edad > 60, el estadio III/IV, y el tipo nodular se asociaron significativamente al desarrollo de un CNC. Tras el análisis multivariado, solo la edad > 60 (hazard ratio [HR] 3,4; intervalo de confianza [IC] 95% HR:1,5-7,6) y el subtipo nodular de melanoma (HR 2,2; IC 95% HR:1,0-4,8) se mantuvieron en el modelo predictivo final. Conclusiones Nuestros resultados sugieren que unos niveles de vitamina D deficientes en el diagnóstico de melanoma no se asocian a un mayor riesgo de desarrollar un CNC. Sin embargo, en una edad > 60 y el subtipo nodular sí que aumentan el riesgo de desarrollar un CNC (AU)

Background Vitamin D deficiency associates with the risk of developing many diseases, including cancer. At the molecular level, vitamin D appears to have an antineoplastic effect. However, the role of vitamin D deficiency in cancer pathogenesis remains unelucidated and numerous studies have resulted in discordant results. This study aimed to determine whether vitamin D deficiency during melanoma diagnosis increases the risk of developing non-cutaneous second primary cancers (SPC). Materials and methods A retrospective study on 663 patients diagnosed with melanoma between 1 January 2011 and 31 October 2022. The effect of each variable on the development of a subsequent non-cutaneous cancer was performed using Kaplan–Meier curves and differences were assessed by log-rank tests. Cox proportional hazard univariate and multivariate models were used to quantify the effect of each variable in the time to develop a non-cutaneous neoplasia. Results Out of 663 patients, 34 developed a non-cutaneous SPC. There was no statistically significant association between vitamin D levels and non-cutaneous SPC development (log-rank, p=0.761). Age>60 years, stage III/IV, and nodular melanoma subtype were significantly associated with the development of a SPC. After multivariate analysis, only age>60 years (HR 3.4; HR CI 95%: 1.5–7.6) and nodular melanoma subtype (HR 2.2; HR CI 95%: 1.0–4.8) were included in the final model. Conclusions Our results suggest that vitamin D deficiency is not associated with an increased risk of developing non-cutaneous SPC in melanoma patients. However, age over 60 years and nodular melanoma subtype increase the risk for non-cutaneous SPC development (AU)

Apparent Variation in Measurement Size of Colorectal Cancer Metastases to the Liver on Dual Contrast MRI.

PURPOSE: The aim of this study was to formally investigate the apparent variation in lesion size of hepatic metastatic lesions from colorectal cancer on hepatobiliary phase (HBP) and dual contrast images of magnetic resonance imaging performed with both hepatobiliary and extracellular contrast agents. METHODS: Patients with known colorectal carcinoma who had undergone dual contrast liver magnetic resonance imaging were identified in our institutional database. Metastatic lesions were measured semiautomatically on both HBP and dual contrast images with a custom software tool that automatically identifies the lesion edge and thereby the lesion diameter. Lesion measurements from both sets of images were compared with a Student t test and Bland-Altman analysis. Lesions were also measured on both HBP and dual contrast images by 2 fellowship-trained abdominal radiologists. Measurements from the software and radiologists were compared with a Student t test and Bland-Altman analysis; interreader agreement was evaluated with the intraclass correlation coefficient. RESULTS: A total of 70 liver lesions in 39 patients was identified. Software-based measurements were significantly larger on HBP than dual contrast images ( P < 0.001), with a mean lesion size of 10.9 ± 4.2 mm for HBP and 10.5 ± 4.2 mm for dual contrast measurements. Radiologist-based measurements showed a similar trend, with HBP measurements being significantly larger than dual contrast measurements ( P < 0.001). Bland-Altman analysis indicated a mean bias ± 2 SD of +0.4 ± 1.6 mm for software-based measurements and +0.9 ± 2.9 mm and +0.7 ± 2.1 mm for readers 1 and 2, respectively. The intraclass correlation coefficient for interreader agreement was 0.9. CONCLUSIONS: Both software-based and radiologist-based measurements of colorectal cancer liver metastases are significantly larger on HBP than dual contrast images. Based on these findings, we recommend that longitudinal assessment be performed consistently on either HBP or dual contrast phases to avoid introduction of avoidable variability.

Nodular Type but Not Vitamin D Levels Increases the Risk of Second Primary Cancers in Melanoma Patients: An Observational Study of 663 Patients. / [Artículo traducido] El melanoma de tipo nodular pero no los niveles de vitamina D aumenta el riesgo de desarrollar una segunda neoplasia no cutánea en pacientes con un melanoma: estudio observacional de 663 pacientes.

BACKGROUND: Vitamin D deficiency associates with the risk of developing many diseases, including cancer. At the molecular level, vitamin D appears to have an antineoplastic effect. However, the role of vitamin D deficiency in cancer pathogenesis remains unelucidated and numerous studies have resulted in discordant results. This study aimed to determine whether vitamin D deficiency during melanoma diagnosis increases the risk of developing non-cutaneous second primary cancers (SPC). MATERIALS AND METHODS: A retrospective study on 663 patients diagnosed with melanoma between 1 January 2011 and 31 October 2022. The effect of each variable on the development of a subsequent non-cutaneous cancer was performed using Kaplan-Meier curves and differences were assessed by log-rank tests. Cox proportional hazard univariate and multivariate models were used to quantify the effect of each variable in the time to develop a non-cutaneous neoplasia. RESULTS: Out of 663 patients, 34 developed a non-cutaneous SPC. There was no statistically significant association between vitamin D levels and non-cutaneous SPC development (log-rank, p=0.761). Age>60 years, stage III/IV, and nodular melanoma subtype were significantly associated with the development of a SPC. After multivariate analysis, only age>60 years (HR 3.4; HR CI 95%: 1.5-7.6) and nodular melanoma subtype (HR 2.2; HR CI 95%: 1.0-4.8) were included in the final model. CONCLUSIONS: Our results suggest that vitamin D deficiency is not associated with an increased risk of developing non-cutaneous SPC in melanoma patients. However, age over 60 years and nodular melanoma subtype increase the risk for non-cutaneous SPC development.

Nodular type but not vitamin D levels increases the risk of second primary cancers in melanoma patients: An observational study of 663 patients.

BACKGROUND: Vitamin D deficiency associates with the risk of developing many diseases, including cancer. At the molecular level, vitamin D appears to have an antineoplastic effect. However, the role of vitamin D deficiency in cancer pathogenesis remains unelucidated and numerous studies have resulted in discordant results. This study aimed to determine whether vitamin D deficiency during melanoma diagnosis increases the risk of developing non-cutaneous second primary cancers (SPC). MATERIALS AND METHODS: A retrospective study on 663 patients diagnosed with melanoma between 1 January 2011 and 31 October 2022. The effect of each variable on the development of a subsequent non-cutaneous cancer was performed using Kaplan-Meier curves and differences were assessed by log-rank tests. Cox proportional hazard univariate and multivariate models were used to quantify the effect of each variable in the time to develop a non-cutaneous neoplasia. RESULTS: Out of 663 patients, 34 developed a non-cutaneous SPC. There was no statistically significant association between vitamin D levels and non-cutaneous SPC development (log-rank, p=0.761). Age>60 years, stage III/IV, and nodular melanoma subtype were significantly associated with the development of a SPC. After multivariate analysis, only age>60 years (HR 3.4; HR CI 95%: 1.5-7.6) and nodular melanoma subtype (HR 2.2; HR CI 95%: 1.0-4.8) were included in the final model. CONCLUSIONS: Our results suggest that vitamin D deficiency is not associated with an increased risk of developing non-cutaneous SPC in melanoma patients. However, age over 60 years and nodular melanoma subtype increase the risk for non-cutaneous SPC development.

PD-1 receptor outside the main paradigm: tumour-intrinsic role and clinical implications for checkpoint blockade.

Blocking the inhibitory receptor PD-1 on antitumour T lymphocytes is the main rationale underlying the clinical successes of cancer immunotherapies with checkpoint inhibitor (CI) antibodies (Abs). Besides this main paradigm, there is recent evidence of unconventional and "ectopic" signalling pathways of PD-1, found to be expressed not only by lymphocytes but also by peculiar subsets of cancer cells. Several groups reported on the tumour-intrinsic role of PD-1 in multiple settings, including melanoma, hepatocellular, thyroid, lung, pancreatic and colorectal cancer. Its functional activity appears intriguing but is not yet conclusively clarified. The initial studies are, in fact, supporting either a pro-tumourigenic role involved in chemoresistance and disease relapse or, oppositely, tumour-suppressive functions. The implications connected to the therapeutic administration of PD-1 blocking Abs are, of course, potentially relevant, respectively inferring an anti-tumour activity contrasting PD-1+ tumourigenic cells or a pro-tumoural effect by tackling PD-1 tumour suppressive signalling. The progressive exploration and consideration of this new paradigm of tumour-intrinsic PD-1 signalling may improve the interpretation of the observed clinical effects by anti-PD-1 Abs, likely resulting from multiple cumulative activities, and might provide important bases for dedicated clinical studies that take into account such composite roles of PD-1.

Differentiation of benign from malignant solid renal lesions with MRI-based radiomics and machine learning.

BACKGROUND: Solid renal masses are often indeterminate for benignity versus malignancy on magnetic resonance imaging. Such masses are typically evaluated with either percutaneous biopsy or surgical resection. Percutaneous biopsy can be non-diagnostic and some surgically resected lesions are inadvertently benign. PURPOSE: To assess the performance of ten machine learning (ML) algorithms trained with MRI-based radiomics features in distinguishing benign from malignant solid renal masses. METHODS: Patients with solid renal masses identified on pre-intervention MRI were curated from our institutional database. Masses with a definitive diagnosis via imaging (for angiomyolipomas) or via biopsy or surgical resection (for oncocytomas or renal cell carcinomas) were selected. Each mass was segmented for both T2- and post-contrast T1-weighted images. Radiomics features were derived from the segmented masses for each imaging sequence. Ten ML algorithms were trained with the radiomics features gleaned from each MR sequence, as well as the combination of MR sequences. RESULTS: In total, 182 renal masses in 160 patients were included in the study. The support vector machine algorithm trained on radiomics features from T2-weighted images performed superiorly, with an accuracy of 0.80 and an area under the curve (AUC) of 0.79. Linear discriminant analysis (accuracy = 0.84 and AUC = 0.77) and logistic regression (accuracy = 0.78 and AUC = 0.78) algorithms trained on T2-based radiomics features performed similarly. ML algorithms trained on radiomics features from post-contrast T1-weighted images or the combination of radiomics features from T2- and post-contrast T1-weighted images yielded lower performance. CONCLUSION: Machine learning models trained with radiomics features derived from T2-weighted images can provide high accuracy for distinguishing benign from malignant solid renal masses. CLINICAL IMPACT: Machine learning models derived from MRI-based radiomics features may improve the clinical management of solid renal masses and have the potential to reduce the frequency with which benign solid renal masses are biopsied or surgically resected.

Pancreatic cancer prognosis is predicted by an ATAC-array technology for assessing chromatin accessibility.

Unlike other malignancies, therapeutic options in pancreatic ductal adenocarcinoma (PDAC) are largely limited to cytotoxic chemotherapy without the benefit of molecular markers predicting response. Here we report tumor-cell-intrinsic chromatin accessibility patterns of treatment-naïve surgically resected PDAC tumors that were subsequently treated with (Gem)/Abraxane adjuvant chemotherapy. By ATAC-seq analyses of EpCAM+ PDAC malignant epithelial cells sorted from 54 freshly resected human tumors, we show here the discovery of a signature of 1092 chromatin loci displaying differential accessibility between patients with disease free survival (DFS) < 1 year and patients with DFS > 1 year. Analyzing transcription factor (TF) binding motifs within these loci, we identify two TFs (ZKSCAN1 and HNF1b) displaying differential nuclear localization between patients with short vs. long DFS. We further develop a chromatin accessibility microarray methodology termed "ATAC-array", an easy-to-use platform obviating the time and cost of next generation sequencing. Applying this methodology to the original ATAC-seq libraries as well as independent libraries generated from patient-derived organoids, we validate ATAC-array technology in both the original ATAC-seq cohort as well as in an independent validation cohort. We conclude that PDAC prognosis can be predicted by ATAC-array, which represents a low-cost, clinically feasible technology for assessing chromatin accessibility profiles.

Accessory Tragus: A Rare Congenital Anomaly in a Dog.

Accessory tragus is a congenital malformation of part of the external ear, commonly reported in humans. Clinically, it is a benign, cutaneous mass located anywhere between the tragus of the ear and the angle of the mouth, along the migratory path of the first branchial arch. An accessory tragus was diagnosed in an otherwise healthy six-month-old male castrated American pit bull terrier that had a haired, pedunculated cutaneous mass on the left maxillary region from birth. Histologically, the mass was a polypoid extension of histologically normal haired skin with a central core of subcutaneous adipose tissue and well-differentiated elastic cartilage. To the authors' knowledge, this is the first report of this lesion in a non-human species. Retrospective examination of records from 2008 to 2018 at the Washington Animal Disease Diagnostic Laboratory failed to identify any other case. As accessory tragus in humans is commonly linked with other congenital anomalies and syndromes, recognition of this lesion in animals may aid in early discovery of other congenital defects and inform adequate excision of the lesion to prevent chondrodermatitis.

Retrospective Data Analysis and Literature Review for a Development of Enhanced Recovery after Surgery Pathway for Anterior Cervical Discectomy and Fusion.

Objective While enhanced recovery after surgery (ERAS) protocols are associated with shorter length of stay and improved outcomes in multiple surgical specialties, its application to spine surgery has been limited. Anterior cervical discectomy and fusion (ACDF) is a common spinal procedure with a relative efficacy and safety profile that makes it suitable for the application of ERAS principles. Reviewing our outcomes and practice and incorporating evidence-based clinical studies, we propose the development of an ERAS pathway for ACDF. Methods This is a retrospective review of ACDF cases performed at a single institution by a single surgeon from 2014 to 2017. Primary outcome measures included length of stay, complications, and 30-day readmission rates. The 1- and 2-level and the 3- and 4-level groups were also each consolidated into a single cohort for comparison. A comprehensive review of evidence-based literature pertaining to ACDF was then performed. Best-practice recommendations derived from the literature were incorporated into the proposed ERAS protocol. Results In this series of 75 1-level, 77 2-level, 44 3-level and 20 4-level ACDF procedures, the average surgical time (minutes) was 68, 90, 118 and 141; length of stay (days) was 1, 1, 1.4, and 1.7; drain usage (%) was 1.3, 2.6, 13.6 and 10; and 30-day readmission rates (%) were 2.7, 3.9, 4.5, and 15, respectively. Combining the 1- and 2-level as a single group and 3- and 4-level as another cohort, the 3- and 4-level cohort had a significantly higher rate of drain usage and estimated blood loss (EBL) but there was not a difference in length-of-stay, complications or 30-day readmission rates. Conclusions Given the relative equivalent safety profile between 1- and 2-level as compared to 3- and 4-level ACDF, the proposed ERAS pathway can be applied to all patients, and not just restricted to 1-level or 2-level ACDF. Taking into account feasibility parameters as deduced from a review of institutional outcomes, this pathway can streamline same-day discharge and improve the patient experience. Its success will be predicated on an iterative improvement process deriving from optimal prospective outcome measurements.

Mononeuropathy due to Entrapment of Dorsal Cutaneous Peroneal Nerve: Clinical, Electrophysiological, and Imaging Findings.

Peroneal neuropathy is the most common mononeuropathy encountered in the lower extremities. Isolated injuries to the dorsal cutaneous peroneal nerve (DCPN) are uncommon, and most of the reported cases are due to trauma or iatrogenic causes. We report a case of a middle-aged woman who presented with a nine-month history of tingling sensation over the dorsum of her left foot with normal electromyography (EMG) findings and was subsequently diagnosed with entrapment of the DCPN at the ankle by ultrasonographic examination.

Low and high body mass index in hidradenitis suppurativa patients-different subtypes?

INTRODUCTION: Overweight is a well-established risk factor for hidradenitis suppurativa (HS). In this cross-sectional study, we compare HS patients with a high body mass index (BMI) with HS patients with a low BMI to investigate differences in disease characteristics. MATERIALS AND METHOD: Patients were recruited from 17 dermatological centres from four continents. A total of 246 patients with a BMI below 25 were compared to 205 patients with a BMI of above 35. RESULTS: Patients with a high BMI suffered more severe disease (Hurley, physician global assessment, number of areas affected and patient-reported severity (PRS), P < 0.001 for all). There was no difference in smoking (P = 0.783) nor in family history (P = 0.088). In both low and high BMI patients, early onset of HS was a predictor of positive family history (P < 0.001, for each). For low BMI patients, an increase in BMI significantly increased PRS (P < 0.001). For patients with a high BMI, number of pack-years significantly increased PRS (P = 0.001). Cluster analysis of eruption patterns was location specific for low BMI patients but severity specific for high BMI patients. DISCUSSION: Patients with a low and high BMI could represent two clinically different subtypes. We suggest a non-linear relationship between BMI and impact of HS. As patients go from a low BMI patient to a high BMI patient (or from high to low), eruption patterns and risk factors may change.

The effect of extracellular acidosis on the behaviour of mesenchymal stem cells in vitro.

The stem cell fraction of a cell population is finely tuned by stimuli from the external microenvironment. Among these stimuli, a decrease of extracellular pH (pHe) may occur in a variety of physiological and pathological conditions, including hypoxia and inflammation. In this study, by using bone marrow stem cells and dental pulp stem cells, we provided evidence that extracellular acidosis endows the maintenance of stemness in mesenchymal cells. Indeed, continuous exposure for 21 d to low pHe (6.5-6.8) conditions impaired the osteogenic differentiation of both cell types. Moreover, the exposure to low pHe, for 1 and up to 7 d, induced the expression of stemness-related genes and proteins, drove cells to reside in the quiescent G0 alert state and enhanced their ability to form floating spheres. The pre-conditioning with extracellular acidosis for 7 d did not affect the differentiation potential of dental pulp stem cells since, when the cells were cultured again at physiological pHe, their multilineage potential was almost unmodified. Our data provided evidence of the role of extracellular acidosis as a modulator of the stemness of mesenchymal cells. This condition is commonly found both in systemic and local bone conditions, hence underlining the relevance of this phenomenon for a better comprehension of bone healing and regeneration.

Association between markers of bone loss and urinary lithogenic risk factors in osteopenic postmenopausal women.

In this study, we explored if urinary lithogenic risk parameters could have some application for monitoring bone health status. We recruited 20 women with postmenopausal osteopenia and a negative medical history for nephrolithiasis. Markers of lithogenic risk were evaluated on 24-h urine and fastingmorning urine. Serum levels of bone turnover markers (BTM) were measured in fasting-blood samples. We found that cross-linked telopeptide of type I collagen (CTX) was significantly correlated with 24-h calcium excretion. N-terminal propeptide of type I procollagen (PINP) correlated with 24-h excretion of potassium, calcium and citrate. CTX had considerably increased in patients with pH less than 5.5. Low citrate levels (less than 3.3 mmol/24 h) were associated with lower levels of CTX and PINP. Our findings suggest that a low-grade acidosis and some lithogenic risk factors are detectable in a proportion of patients with postmenopausal osteopenia. Further studies are necessary to confirm that this evaluation could be clinically relevant.

A consensus-based practical and daily guide for the treatment of acne patients.

BACKGROUND: Many current guidelines provide detailed evidence-based recommendations for acne treatment. OBJECTIVE: To create consensus-based, simple, easy-to-use algorithms for clinical acne treatment in daily office-based practice and to provide checklists to assist in determining why a patient may not have responded to treatment and what action to take. METHODS: Existing treatment guidelines and consensus papers were reviewed. The information in them was extracted and simplified according to daily clinical practice needs using a consensus-based approach and based on the authors' clinical expertise. RESULTS: As outcomes, separate simple algorithms are presented for the treatment of predominant comedonal, predominant papulopustular and nodular/conglobate acne. Patients with predominant comedonal acne should initially be treated with a topical retinoid, azelaic acid or salicylic acid. Fixed combination topicals are recommended for patients with predominant papulopustular acne with treatment tailored according to the severity of disease. Treatment recommendations for nodular/conglobate acne include oral isotretinoin or fixed combinations plus oral antibiotics in men, and these options may be supplemented with oral anti-androgenic hormonal therapy in women. Further decisions regarding treatment responses should be evaluated 8 weeks after treatment initiation in patients with predominant comedonal or papulopustular acne and 12 weeks after in those with nodular/conglobate acne. Maintenance therapy with a topical retinoid or azelaic acid should be commenced once a patient is clear or almost clear of their acne to prevent the disease from recurring. The principal explanations for lack of treatment response fall into 5 main categories: disease progression, non-drug-related reasons, drug-related reasons, poor adherence, and adverse events. CONCLUSION: This practical guide provides dermatologists with treatment algorithms adapted to different clinical features of acne which are simple and easy to use in daily clinical practice. The checklists to establish the causes for a lack of treatment response and subsequent action to take will facilitate successful acne management.

Reproductive and population parameters of spiny dogfish Squalus acanthias in the south-western Atlantic Ocean.

The objective of this study was to estimate reproductive and population parameters of the spiny dogfish Squalus acanthias for the south-western Atlantic Ocean. In total, 2714 specimens (1616 males and 1098 females) were collected from surveys carried out using research vessels. Males ranged from 225 to 861 mm total length (LT ) and females from 235 to 925 mm LT . The size at maturity of females (651 mm) was significantly greater than that of males (565 mm). The maximum proportion of mature individuals (Pmax ) of the gestation ogive was <1, which indicates that a proportion of mature females was not in gestation. This inactivity may be explained by the occurrence of resting periods between cycles or by the asynchrony of the reproductive cycle. The estimated Pmax for the maternity ogive suggested that about one third of mature females were in the maternity stage (i.e. with embryos >156 mm). The temporal and spatial co-occurrence of non-gravid adult females at different stages of ovarian development, as well as gravid females at all embryonic development stages would indicate that the female reproductive cycle in the south-western Atlantic Ocean is asynchronous. The results indicate that S. acanthias is susceptible to fishing pressure on account of its length at maturity, extended reproductive cycles and low fecundity.

Trophic ecology of yellownose skate Zearaja chilensis, a top predator in the south-western Atlantic Ocean.

The diet and trophic level (TL ) of the yellownose skate Zearaja chilensis in the south-western Atlantic Ocean (35°-54° S), and how these varied in relation to body size, sex, maturity stage, depth and region were determined by analysis of stomach contents. From 776 specimens analysed, 671 (86·5%) ranging from 180 to 1190 mm total length (LT ) had prey in their stomachs. The diet was dominated by fishes, mainly the notothenioid Patagonotothen ramsayi and the Argentine hake Merluccius hubbsi. The consumption of fishes and crabs increased with increasing predator size, and these preys were more important in the north than in the south. Isopods and other crustaceans were consumed more in the south and their consumption decreased as the size of Z. chilensis increased. The TL of Z. chilensis increased with LT from 4·29 to 4·59 (mean 4·53), confirming their ecological role as a top predator. The small and large size classes exhibited a low diet overlap and the highest spatial segregation, whereas medium and large specimens had higher co-occurrence and dietary overlap indices. A clear distinction in tooth shape was noted between sexes in adult specimens, with males having longer cusps. This sexual heterodonty may be related to reproductive behaviour, increasing the grasping ability of males during courtship, because there were no differences in diet between the sexes.