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Melanocytic lesions are instable tumors, the genome of which and its changes determinate their morphology and biological properties. Intermediate lesions share histomorphological features of both, nevi and melanoma. Melanocytomas represent a group of them separated on the basis of recent molecular-biological studies. The article summarizes benign, intermediate, malignant and combined melanocytic skin lesions and offers practical recommendations for diagnosis.

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Spitz tumors represent a heterogeneous group of challenging melanocytic neoplasms, displaying a range of biological behaviors, spanning from benign lesions, Spitz nevi (SN) to Spitz melanomas (SM), with intermediate lesions in between known as atypical Spitz tumors (AST). They are histologically characterized by large epithelioid and/or spindled melanocytes arranged in fascicles or nests, often associated with characteristic epidermal hyperplasia and fibrovascular stromal changes. In the last decade, the detection of mutually exclusive structural rearrangements involving receptor tyrosine kinases ROS1, ALK, NTRK1, NTRK2, NTRK3, RET, MET, serine threonine kinases BRAF and MAP3K8, or HRAS mutation, led to a clinical, morphological and molecular based classification of Spitz tumors. The recognition of some reproducible histological features can help dermatopathologist in assessing these lesions and can provide clues to predict the underlying molecular driver. In this review, we will focus on clinical and morphological findings in molecular Spitz tumor subgroups.

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OBJECTIVE: Time-varying treatments are common in observational studies. However, when assessing treatment effects, the methodological framework has not been systematically established for handling time-varying treatments. This study aimed to examine the current methods for dealing with time-varying treatments in observational studies and developed practical recommendations. METHODS: We searched PubMed from 2000 to 2021 for methodological articles about time-varying treatments, and qualitatively summarized the current methods for handling time-varying treatments. Subsequently, we developed practical recommendations through interactive internal group discussions and consensus by a panel of external experts. RESULTS: Of the 36 eligible reports (22 methodological reviews, 10 original studies, 2 tutorials and 2 commentaries), most examined statistical methods for time-varying treatments, and only a few discussed the overarching methodological process. Generally, there were three methodological components to handle time-varying treatments. These included the specification of treatment which may be categorized as three scenarios (i.e., time-independent treatment, static treatment regime, or dynamic treatment regime); definition of treatment status which could involve three approaches (i.e., intention-to-treat, per-protocol, or as-treated approach); and selection of analytic methods. Based on the review results, a methodological workflow and a set of practical recommendations were proposed through two consensus meetings. CONCLUSIONS: There is no consensus process for assessing treatment effects in observational studies with time-varying treatments. Previous efforts were dedicated to developing statistical methods. Our study proposed a stepwise workflow with practical recommendations to assist the practice.

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Physical literacy (PL) has been readily accepted and integrated globally, including organizations affording services to individuals experiencing disability. Despite its uptake, recent research has illustrated that understandings of PL reflect the normative standards of those who do not experience disability, leading to practices that diminish the unique and embodied capability of others while simultaneously validating ableism. While a shift towards recognizing and valuing the heterogeneity associated with PL has recently occurred, the ableist narrative persists. As a result, the operationalization of PL directly contradicts its conceptualization, fostering a physical activity climate that continues to marginalize individuals experiencing disability. With this in mind, this paper critically unpacks PL, challenging the existing ableist narrative and offering suggestions to heighten the level of inclusivity that underscores PL. Pathways, where physical activity professionals contribute to reproducing ableism, will be discussed.

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BACKGROUND: Precise prognostication is the key to optimum and effective treatment planning for early-stage hormone receptor (HR) positive, HER2/neu negative breast cancer patients. Differences in the breast cancer incidence and tumor anatomical features at diagnosis, pharmacogenomics data between Western and Indian women along with the vast diversity in the economic status and differences in insurance policies of these regions; suggest recommendations put forward for Western women might not be applicable to Indian/Asian women. Opinions from oncologists through a voting survey on various prognostic factors/tools to be considered for planning adjuvant therapy are consolidated in this report for the benefit of oncologists of the sub-continent, SAARC and Asia's LMIC (low and middle-income countries). METHODS: A three-phase DELPHI survey was conducted to collect opinions on prognostic factors considered for planning adjuvant therapy in early-stage HR+/HER2/neu negative breast cancer patients. A panel of 25 oncologists with expertise in breast cancer participated in the survey conducted in 2021. The experts provided opinions as 'agree' or disagree' or 'not sure' in phases-1 and 2 which were conducted virtually; in the final phase-3, all the panel experts met in person and concluded the survey. RESULTS: Opinions on 41 statements related to prognostic factors/tools and their implications in planning adjuvant endocrine/chemotherapy were collected. All the statements were supported by the latest data from the clinical trials (prospective/retrospective). The statements with opinions of consensus less than 66% were disseminated in phase-2, and later in phase-3 with supporting literature. In phase-3, all the opinions from panelists were consolidated and guidelines were framed. CONCLUSIONS: This consensus guideline will assist oncologists of India, SAARC and LMIC countries in informed clinical decision-making on adjuvant treatment in early HR+/HER2/neu negative breast cancer patients.

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Based on the growing evidence of the therapeutic role of high-fat ketogenic dietary therapies (KDTs) for neurological diseases and on the protective effect of the Mediterranean diet (MD), it could be important to delineate a Mediterranean version of KDTs in order to maintain a high ketogenic ratio, and thus avoid side effects, especially in patients requiring long-term treatment. This narrative review aims to explore the existing literature on this topic and to elaborate recommendations for a Mediterranean version of the KDTs. It presents practical suggestions based on MD principles, which consist of key elements for the selection of foods (both from quantitative and qualitative prospective), and indications of the relative proportions and consumption frequency of the main food groups that constitute the Mediterranean version of the KDTs. We suggest the adoption of a Mediterranean version of ketogenic diets in order to benefit from the multiple protective effects of the MD. This translates to: (i) a preferential use of olive oil and vegetable fat sources in general; (ii) the limitation of foods rich in saturated fatty acids; (iii) the encouragement of high biological value protein sources; (iv) inserting fruit and vegetables at every meal possible, varying their choices according to seasonality.

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Malnutrition is a frequent problem in cancer patients, which leads to prolonged and repeated hospitalizations, increased treatment-related toxicity, reduced response to cancer treatment, impaired quality of life, a worse overall prognosis and the avoidable waste of health care resources. Despite being perceived as a limiting factor in oncologic treatments by both oncologists and patients, there is still a considerable gap between need and actual delivery of nutrition care, and attitudes still vary considerably among health care professionals. In the last 5 years, the Italian Intersociety Working Group for Nutritional Support in Cancer Patients (WG), has repeatedly revisited this issue and has concluded that some improvement in nutritional care in Italy has occurred, at least with regard to awareness and institutional activities. In the same period, new international guidelines for the management of malnutrition and cachexia have been released. Despite these valuable initiatives, effective structural strategies and concrete actions aimed at facing the challenging issues of nutritional care in oncology are still needed, requiring the active participation of scientific societies and health authorities. As a continuation of the WG's work, we have reviewed available data present in the literature from January 2016 to September 2021, together with the most recent guidelines issued by scientific societies and health authorities, thus providing an update of the 2016 WG practical recommendations, with suggestions for new areas/issues for possible improvement and implementation.

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BACKGROUND: Cryoglobulins are immunoglobulins that precipitate at low temperature. Strict preanalytical and analytical conditions are critical for the detection of cryoglobulins. CONTENT: This review will focus on practical recommendations for detection and characterization of cryoglobulins and the technical problems that may be encountered. A laboratory report format is proposed for presentation of these results that includes the parameters necessary for an optimal interpretation by clinicians. The first step of detection of cryoglobulins can be performed in any laboratory that has a 37 °C incubator and temperature-controlled centrifuge. The second step is the characterization of cryoglobulins, and this often must be performed in more specialized laboratories. Characterization includes immunoglobulin typing, for the classification of cryoglobulins and potential underlying disease(s); quantification of immunoglobulins and rheumatoid factor in the cryoprecipitate to define the pathogenicity; and quantification of serum complement, which is useful for diagnosis. SUMMARY: These practical recommendations will be useful for the accurate detection of cryoglobulins, an essential step for the diagnosis of cryoglobulinemic vasculitis, a rare but severe clinical manifestation of cryoglobulins.

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Medical cannabis access has been legalized in more than 30 countries worldwide and popularity among patients is increasing rapidly. Cannabinoid-based treatments have been shown to be beneficial for several symptoms such as chemotherapy-induced nausea and vomiting, spasticity, chronic pain, intractable seizures and insomnia, yet high-quality clinical trials are still limited. As millions of patients now have legal access to medical cannabis, little information is available about the development of best clinical practices and an effective medical cannabis clinic model. A medical cannabis clinic is an innovative and emergent practice model that may be necessary to bridge the gap between patient and healthcare provider interest and existing barriers to the prescription of medical cannabis treatments, such as limited medical education, lack of high-quality clinical research and challenging or evolving regulatory frameworks. In this paper, we describe the model of care and organization of a dedicated medical cannabis clinic operating in Quebec, Canada since 2014. We share the principles of medical cannabis practice, including the structure of its medical and support team, clinic organisation and procedure guidelines. Key clinic statistics and patient demographics are shared with year by year comparison. Operating since 2014, the clinic has endured a rapidly changing regulatory landscape in Canada, overcoming numerous challenges including medical and social stigma, limited funding, resources and institutional support combined with a high demand for services. To support medical cannabis leaders globally, an important knowledge-sharing is required. The clinic has expanded to a network of four clinic sites across Quebec and offers continuing education and preceptorships to health care providers and trainees as well as research services to both academic and industry partners. The description of the clinic offers guidance on medical cannabis treatment and care and discusses possible solutions to associated challenges. The clinic model of care can be adapted to different healthcare settings and regulatory frameworks; it may assist physicians and health care providers in the development of medical cannabis clinics or the implementation of best practices as medical cannabis access continues to evolve.

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The current COVID-19 pandemic requires revisiting our current approach to major blood disorders, including ITP (Immune Thrombocytopenia), stirring up the production of several disease-specific practical guidelines. This report describes an updated version of consensus-based practical guidelines on the management of ITP, adapted to the Italian health system and social context. It highlights the role of the hematologist in offering guidance for choosing differentiated approaches in relation to specific circumstances and is intended to provide them with a useful tool for sharing the decision-making process with their patients. Probably, the greatest risk to avoid for a patient with suspected, ongoing or relapsed ITP - that is not severe enough to place him or her at risk for major bleeding - is to be infected in non-hospital and hospital healthcare settings. This risk must be carefully considered when adapting the diagnostic and therapeutic approach. More in detail, the document first addresses the appropriate management for COVID-19 negative patients with newly diagnosed ITP or who experience a relapse of previous ITP, according to first and second lines of treatment and then the management of COVID-19 positive patients according to their severity, from paucisymptomatic to those requiring admission to Intensive Cure Units (ICU). The pros and cons of the different treatments required to correct platelet count are discussed, as are some specific situations, including chronic ITP, splenectomy, thromboembolic complication and anti COVID-19 vaccination.

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BACKGROUND AND AIMS: The objective of this update of the EAU-ESPU guidelines recommendations for nocturnal enuresis was to review the recent published literature of studies, reviews, guidelines regarding the etiology, diagnosis and treatment options of nocturnal enuresis and transform the information into a practical recommendation strategy for the general practitioner, pediatrician, pediatric urologist and urologist. MATERIAL AND METHODS: Since 2012 a monthly literature search using Scopus® was performed and the relevant literature was reviewed and prospectively registered on the European Urology bedwetting enuresis resource center (http://bedwetting.europeanurology.com/). In addition, guideline papers and statements of the European Society for Paediatric Urology (ESPU), the European Association of Urology (EAU), the National Institute for Health and Care Excellence (NICE) and the International Children Continence Society (ICCS) were used to update the knowledge and evidence resulting in this practical recommendation strategy. Recommendations have been discussed and agreed within the working group of the EAU-ESPU guidelines committee members. RESULTS: The recommendations focus to place the child and his family in a control position. Pragmatic analysis is made of the bedwetting problem by collecting voiding and drinking habits during the day, measuring nighttime urine production and identification of possible risk factors such as high-volume evening drinking, nighttime overactive bladder, behavioral or psychological problems or sleep disordered breathing. A questionnaire will help to identify those risk factors. CONCLUSION: Motivation of the child is important for success. Continuous involvement of the child and the family in the treatment will improve treatment compliance, success and patient satisfaction.

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OBJECTIVES: People with a history of injecting drugs have high prevalence of hepatitis C virus (HCV) infection, and many have opioid use disorder (OUD). Modern HCV therapies with improved efficacy and tolerability are available, but access is often limited for this group, who may be underserved for health care and face social inequity. This work develops practical steps to improve HCV care in this population. METHODS: Practical steps to improve HCV care in OUD populations were developed based on clinical experience from Spain, structured assessment of published evidence. RESULTS: Options for improving care at engagement/screening stages include patient education programs, strong provider-patient relationship, peer support, and adoption of rapid effective screening tools. To facilitate work up/treatment, start options include simplified work up process, integration of HCV and OUD care, and continuous psychosocial support prior, during, and after HCV treatment. CONCLUSION: It is important to plan on local basis to set up a joint integrated approach between specific drug treatment services and local points of HCV care. The elements for a specific integrated program should be chosen from options identified, including education services, peer input, organization to make HCV screening and treatment easier by co-location of services, and wider access to prescribing direct-acting antiviral (DAA) therapy.

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Hypercholesterolaemia is amongst the most common conditions encountered in the medical profession. It remains one of the key modifiable cardiovascular risk factors and there have been recent advances in the risk stratification methods and treatment options available. In this review, we provide a background into hypercholesterolaemia for non-specialists and consider the merits of the different risk assessment tools available. We also provide detailed considerations as to: i) when to start treatment, ii) what targets to aim for and iii) the role of low density lipoprotein cholesterol.

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Alemtuzumab (Lemtrada®) is a humanized monoclonal antibody indicated for the treatment of adult patients with relapsing-remitting multiple sclerosis with active disease defined by clinical or imaging features. Alemtuzumab demonstrated superior efficacy over active comparator in both treatment naive patients and those with inadequate response to prior therapy. Alemtuzumab is associated with a consistent and manageable safety and tolerability profile. Treatment with alemtuzumab for multiple sclerosis increases the risk for autoimmune adverse events including immune thrombocytopenia (ITP). Complete blood counts with differential should be obtained prior to initiation of treatment and at monthly intervals thereafter for 48 months after the last infusion. After this period of time, testing should be performed based on clinical findings suggestive of ITP. If ITP onset is confirmed, appropriate medical intervention should be promptly initiated, including immediate referral to a specialist. This paper presents the consensus of Belgian multiple sclerosis specialists and hematologists to guide the treating physician with practical recommendations.

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Basal insulin remains the mainstay of treatment of type 2 diabetes when diet changes and exercise in combination with oral drugs and other injectable agents are not sufficient to control hyperglycemia. Insulin therapy should be individualized, and several factors influence the choice of basal insulin; these include pharmacological properties, patient preferences, and lifestyle, as well as health insurance plan formularies. The recent availability of basal insulin formulations with longer durations of action has provided further dosing flexibility; however, patients may need to switch agents throughout therapy for a variety of personal, clinical, or economic reasons. Although a unit-to-unit switching approach is usually recommended, this conversion strategy may not be appropriate for all patients and types of insulin. Glycemic control and risk of hypoglycemia must be closely monitored by health care providers during the switching process. In addition, individual changes in care and formulary coverage need to be adequately addressed in order to enable a smooth transition with optimal outcomes.

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The qualitative-quantitative study investigates the co-existence of barriers and levers to FOBT screening in 5894 individuals reluctant to be screened, identifying operational motivational patterns that may increase screening compliance. Co-occurrence analysis was performed according to three motivational conditions (barriers, levers, or both).Cluster analysis then identified motivational predictors of effective screening. One quarter of the individuals who had refused screening nevertheless expressed at least one motivation towards FOBT. As such, co-existence of barriers and levers within the same individual demonstrates ambivalence tendencies. Intrinsic motivations appear to be the most likely to increase FOBT compliance. This study finds that certain factors well-known to improve CRC screening compliance generally, may not have much impact on reluctant individuals due to ambivalence and contextual nuances. Several practical recommendations to encourage screening participation are offered, such as focusing on levers rather barriers, providing tailored education to improve awareness and readiness, and fostering intrinsic motivation with relevant approaches.

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Abstract: Atherogenic dyslipidemia (DA) is a poorly recognized entity in the current clinical practice guidelines. Due to the frequent lipid alterations associated with this metabolic abnormality in Latin America (LA), we organized a group of experts that has adopted the name of Latin American Association for the study of Lipids (ALALIP), to generate a document for analyzing in LA the prevalence of the lipid profile related to this condition, and to offer practical recommendations for its optimal diagnosis and treatment. Methodology: It was is selected a group of regional experts and, using a modified Delphi methodology, we conducted a comprehensive literature review, with emphasis on studies or reviews that had implications for LA. Subsequently developed a series of key questions about the epidemiology, pathophysiology, diagnosis, and treatment of the AD to be discussed by the group of experts. As a convention those recommendations that had 100% acceptance was consider unanimous; those with at least 80% as for consensus, and of disagreement, those with less than 80%. Results: Although there is no a global study on risk factors that has been made on the basis of a representative sample of the entire population of LA, the systematic analysis of the national health surveys and regional cohort studies based on local population sampling shows a consistent evidence of the high prevalence of the lipid abnormalities that define the AD. The prevalence of low levels of high density lipoprotein cholesterol (HDL-C) ranges from 34.1% (CESCAS I study) to 53.3% (LASO study), with different frequencies between men and women and the selected cut-off point. The prevalence of elevated triglycerides (TRG) varies from 25.5% (LASO study) to 31.2% (National Health Survey of Chile) being always more prevalent in men than in women. Only two studies report the prevalence of AD in LA: the National Health Survey of Mexico 2006 with an 18.3%, and a Venezuelan study that estimates the weighted prevalence of AD in 24.7%. There are multiple causes for these findings: an inadequate nutrition-characterized for high consumption of foods with a high caloric density and a high intake of cholesterol and trans fats-, a sedentary lifestyle, a high prevalence of obesity in the region, and possibly epigenetic changes that make our population more susceptible for having this abnormal lipid profile. Conclusions: Lipid abnormalities that define AD have a high prevalence in LA; the interaction between the style of living, the inheritance, and epigenetic changes possibly are its cause. Since they are considered as an important cause of residual cardiovascular risk, they must be diagnosed and treated actively as a secondary target after reaching the goal for low density lipoprotein-cholesterol (LDL-C). It is important to design a global study of risk factors in our region to let us know the true prevalence of AD and its causes, and to help us in the design of public policies adapted to our reality in a population and individual scale.

Resumen: La dislipidemia aterogénica (DA) es una entidad poco reconocida en las guías de práctica clínica actuales. Debido a las frecuentes alteraciones lipídicas asociadas a esta anomalía metabólica en América Latina (AL), hemos organizado un grupo de expertos que ha adoptado el nombre de Asociación Latinoamericana para el Estudio de Lípidos (ALALIP), para generar un documento en el que se analice la prevalencia en AL del perfil lipídico relacionado con esta afección y ofrecer recomendaciones prácticas para su óptimo diagnóstico y tratamiento. Metodología: Se seleccionó un grupo de expertos regionales y, utilizando una metodología Delphi modificada, se realizó una revisión bibliográfica exhaustiva, con énfasis en estudios o revisiones que tuvieran implicaciones para AL. Posteriormente se desarrolló una serie de preguntas clave sobre la epidemiología, la fisiopatología, el diagnóstico y el tratamiento de la DA, que fueron discutidas por el grupo de expertos. Como convención, las recomendaciones que tuvieron un 100% de aceptación fueron consideradas unánimes; aquellas con al menos el 80% como para el consenso, y de desacuerdo, aquellas con menos del 80%. Resultados: Aunque no existe un estudio global sobre los factores de riesgo que se haya realizado sobre la base de una muestra representativa de toda la población de AL, el análisis sistemático de las encuestas nacionales de salud y los estudios de cohortes regionales evidencian la alta prevalencia de las anormalidades lipídicas que definen la DA. La prevalencia de niveles bajos de colesterol de lipoproteínas de alta densidad (HDL-C) oscila entre el 34.1% (estudio CESCAS I) y el 53.3% (estudio LASO), con diferentes frecuencias entre hombres y mujeres y el punto de corte seleccionado. La prevalencia de triglicéridos elevados (TRG) varía de 25.5% (estudio LASO) a 31.2% (Encuesta Nacional de Salud de Chile) siendo siempre más prevalente en hombres que en mujeres. Sólo dos estudios informan la prevalencia de DA en AL: la Encuesta Nacional de Salud de México 2006 con un 18.3%, y un estudio venezolano que estima la prevalencia ponderada de la DA en 24.7%. Existen múltiples causas para estos hallazgos: una nutrición inadecuada -caracterizada por el alto consumo de alimentos con alta densidad calórica y un alto consumo de colesterol y grasas trans- un estilo de vida sedentario, una alta prevalencia de obesidad en la región y posiblemente cambios epigenéticos que hacen que nuestra población sea más susceptible a tener este perfil lipídico anormal. Conclusiones: Las anomalías lipídicas que definen la DA tienen una alta prevalencia en AL; la interacción entre el estilo de vida, la herencia, y los cambios epigenéticos posiblemente son su causa. Debido a que se consideran una causa importante de riesgo cardiovascular residual, deben ser diagnosticados y tratados activamente como un objetivo secundario después de alcanzar la meta para el colesterol de lipoproteína de baja densidad (LDL-C). Es importante diseñar un estudio global de los factores de riesgo en nuestra región para hacernos conocer la verdadera prevalencia de la DA y sus causas y ayudarnos en el diseño de políticas públicas adaptadas a nuestra realidad en una escala poblacional e individual.

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Myelodysplastic syndromes (mdss) constitute a heterogeneous group of malignant hematologic disorders characterized by marrow dysplasia, ineffective hematopoiesis, peripheral blood cytopenias, and pronounced risk of progression to acute myeloid leukemia. Azacitidine has emerged as an important treatment option and is recommended by the Canadian Consortium on Evidence-Based Care in mds as a first-line therapy for intermediate-2 and high-risk patients not eligible for allogeneic stem cell transplant; however, practical guidance on how to manage patients through treatment is limited. This best practice guideline provides recommendations by a panel of experts from Canadian centres of excellence on the selection and clinical management of mds patients with azacitidine. Familiarity with the referral process, treatment protocols, dose scheduling, treatment expectations, response monitoring, management of treatment breaks and adverse events, and multidisciplinary strategies for patient support will improve the opportunity for optimizing treatment outcomes with azacitidine.