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The summarized guidelines update the 2014 recommendations for the management of AD with phototherapy and systemic therapies. A multidisciplinary workgroup conducted a systematic review and applied the GRADE approach for assessing the certainty of the evidence and formulating and grading recommendations. The workgroup developed 11 recommendations on the management of AD in adults with phototherapy and systemic therapies, including biologics, oral Janus Kinase inhibitors, and other immunomodulatory medications. The evidence supported strong recommendations for the use of dupilumab, tralokinumab, abrocitinib, baricitinib, and upadacitinib and conditional recommendations in favor of using phototherapy, azathioprine, cyclosporine, methotrexate, and mycophenolate, and against the use of systemic corticosteroids. [ABSTRACT FROM AUTHOR]

For people with atopic dermatitis (AD) refractory to topical therapies, treatment with phototherapy and systemic therapies can be considered. Multiple biologic therapies and Janus kinase (JAK)inhibitors have been approved since 2014 to treat AD. These guidelines update the 2014 recommendations for management of AD with phototherapy and systemic therapies. To provide evidence-based recommendations on the use of phototherapy and systemic therapies for AD in adults. A multidisciplinary workgroup conducted a systematic review and applied the GRADE approach for assessing the certainty of evidence and formulating and grading recommendations. The workgroup developed 11 recommendations on the management of AD in adults with phototherapy and systemic agents, including biologics, oral JAK inhibitors, and other immunomodulatory medications. Most randomized controlled trials of phototherapy and systemic therapies for AD are of short duration with subsequent extension studies, limiting comparative long-term efficacy and safety conclusions. We make strong recommendations for the use of dupilumab, tralokinumab, abrocitinib, baricitinib, and upadacitinib. We make conditional recommendations in favor of using phototherapy, azathioprine, cyclosporine, methotrexate, and mycophenolate, and against the use of systemic corticosteroids. [ABSTRACT FROM AUTHOR]

New evidence has emerged since the 2014 guidelines that further informs the management of atopic dermatitis (AD) with topical therapies. These guidelines update the 2014 recommendations for management of AD with topical therapies. To provide evidence-based recommendations related to management of AD in adults using topical treatments. A multidisciplinary workgroup conducted a systematic review and applied the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) approach for assessing the certainty of evidence and formulating and grading recommendations. The workgroup developed 12 recommendations on the management of AD in adults with topical therapies, including nonprescription agents and prescription topical corticosteroids (TCS), calcineurin inhibitors (TCIs), Janus kinase (JAK) inhibitors, phosphodiesterase-4 inhibitors (PDE-4), antimicrobials, and antihistamines. The pragmatic decision to limit the literature review to English-language randomized trials may have excluded data published in other languages and relevant long-term follow-up data. Strong recommendations are made for the use of moisturizers, TCIs, TCS, and topical PDE-4 and JAK inhibitors. Conditional recommendations are made for the use of bathing and wet wrap therapy and against the use of topical antimicrobials, antiseptics, and antihistamines. [ABSTRACT FROM AUTHOR]

The prevalence of anticoagulation treatment is increasing as an aging global population faces a high burden of cardiovascular comorbidities. Direct oral anticoagulants, including factor Xa inhibitors (FXai), are replacing vitamin K antagonists as the most commonly prescribed treatment for reducing risk of thrombotic events. While the risk of FXai-associated spontaneous bleeds is established, less is understood about their management and the effect of treatment on clinical and patient-reported outcomes. The primary objectives of the REVERXaL study are to describe patient characteristics, health care interventions during the acute-care phase, in-hospital outcomes, and associations between timing of reversal/replacement agent administration and in-hospital outcomes. Secondary/exploratory objectives focus on clinical assessments and patient-reported outcome measures (PROMs) at 30 and 90 days. REVERXaL is a multinational, observational study of hospitalized patients with FXai-associated major bleeds in Germany, Japan, the United Kingdom, and the United States. The study includes 2 cohorts of approximately 2000 patients each. Cohort A is a historic cohort for whom medical chart data will be collected from hospitalization to discharge for patients admitted for major bleeds during FXai use within 2 years prior to enrollment of Cohort B. Cohort B will prospectively enroll patients administered any reversal/replacement agent during hospitalization to manage FXai-associated major bleeds and will include the collection of clinical outcomes and PROMs data over 3 months. REVERXaL will generate insights on patient characteristics, treatment approaches, and associated outcomes in patients hospitalized with FXai-associated major bleeds. These data may inform clinical practice and streamline treatment pathways in this population. URL: https://www.clinicaltrials.gov ; unique identifier: NCT06147830. [Display omitted] • Data on patients with FXai-associated bleeds in clinical practice are limited. • REVERXaL is an observational study of patients with FXai-associated major bleeds. • Data will include patient characteristics and treatments across multiple countries. • Clinical and patient-reported outcomes data will be collected for up to 90 days. [ABSTRACT FROM AUTHOR]

Background: Hidradenitis suppurativa (HS) is associated with comorbidities that contribute to poor health, impaired life quality, and mortality risk.Objective: To provide evidence-based screening recommendations for comorbidities linked to HS.Methods: Systematic reviews were performed to summarize evidence on the prevalence and incidence of 30 comorbidities in patients with HS relative to the general population. The screening recommendation for each comorbidity was informed by the consistency and quality of existing studies, disease prevalence, and magnitude of association, as well as benefits, harms, and feasibility of screening. The level of evidence and strength of corresponding screening recommendation were graded by using the Strength of Recommendation Taxonomy (SORT) criteria.Results: Screening is recommended for the following comorbidities: acne, dissecting cellulitis of the scalp, pilonidal disease, pyoderma gangrenosum, depression, generalized anxiety disorder, suicide, smoking, substance use disorder, polycystic ovary syndrome, obesity, dyslipidemia, diabetes mellitus, metabolic syndrome, hypertension, cardiovascular disease, inflammatory bowel disease, spondyloarthritis, and sexual dysfunction. It is also recommended to screen patients with Down syndrome for HS. The decision to screen for specific comorbidities may vary with patient risk factors. The role of the dermatologist in screening varies according to comorbidity.Limitations: Screening recommendations represent one component of a comprehensive care strategy.Conclusions: Dermatologists should support screening efforts to identify comorbid conditions in HS. [ABSTRACT FROM AUTHOR]

• S. oralis, A. naeslundii, A. actinomycetemcomitans demonstrated early colonization. • Secondary colonizers (V. parvula, F. nucleatum) gradually overtook early colonizers. • P. gingivalis dominated in mixed culture after elevated amounts of F. nucleatum. • Multispecies oral biofilm growth is alike on surface-treated titanium and zirconia. Oral bacterial adhesion on dental implant materials has been extensively studied using in vitro systems but has yielded results restricted to in vitro growth patterns due to limitations in species selection, sustained fastidious anaerobe growth, and mixed culture longevity. The aim of this study was to develop an oral bacterial biofilm model consisting of colonizers representative of the oral microbiome exhibiting temporal shifts characteristic of plaque development and maturation in vivo. Streptococcus oralis , Actinomyces naeslundii , Aggregatibacter actinomycetemcomitans , Veillonella parvula , Fusobacterium nucleatum , and Porphyromonas gingivalis were grown in monoculture prior to combination in mixed culture. Commercially pure titanium (cpTi) and yttria-stabilized zirconia (ZrO 2) disks with polished, acid-etched, or sandblasted surfaces were prepared to evaluate oral bacterial adhesion. After 6 h, 1, 3, 7, 14 and 21 days, genomic DNA from planktonic and adherent bacteria was isolated. Quantitative polymerase chain reaction (qPCR) was used to enumerate the amount and proportion of each species. Early-colonizing S. oralis and A. actinomycetemcomitans , dominated after 6 h prior to secondary colonization by F. nucleatum and V. parvula in planktonic (1 day) and sessile (3 days) form. A. naeslundii maintained relatively low but stable bacterial counts throughout testing. After 14 days, late-colonizing P. gingivalis became established in mixed culture and persisted, becoming the dominant species after 21 days. The composition of adherent bacteria across all substrates was statistically similar at all timepoints with notable exceptions including lower S. oralis bacterial counts on polished cpTi (3 days). Within the present model's limitations, multispecies oral bacterial attachment is similar on surface-treated cpTi and ZrO 2. [ABSTRACT FROM AUTHOR]

These guidelines update the 2014 recommendations for management of atopic dermatitis in adults with topical therapies. A multidisciplinary workgroup employed best practices for guideline development, including a systematic review of the evidence and application of the Grading of Recommendations, Assessment, Development, and Evaluation approach for assessing the certainty of the evidence and formulating and grading recommendations. The evidence on atopic dermatitis treatment supported strong recommendations for the use of nonprescription moisturizers, topical calcineurin inhibitors, topical corticosteroids, and topical PDE-4 and JAK inhibitors. Conditional recommendations are made for the use of bathing and wet wrap therapy and against the use of topical antimicrobials, antiseptics, and antihistamines. [ABSTRACT FROM AUTHOR]

Hidradenitis suppurativa is a severe and debilitating dermatologic disease. Clinical management is challenging and consists of both medical and surgical approaches, which must often be combined for best outcomes. Therapeutic approaches have evolved rapidly in the last decade and include the use of topical therapies, systemic antibiotics, hormonal therapies, and a wide range of immunomodulating medications. An evidence-based guideline is presented to support health care practitioners as they select optimal medical management strategies and is reviewed in this second part of the management guidelines. A therapeutic algorithm informed by the evidence available at the time of the review is provided. [ABSTRACT FROM AUTHOR]

Hidradenitis suppurativa is a chronic inflammatory disorder affecting hair follicles, with profoundly negative impact on patient quality of life. Evidence informing ideal evaluation and management of patients with hidradenitis suppurativa is still sparse in many areas, but it has grown substantially in the last decade. Part I of this evidence-based guideline is presented to support health care practitioners as they select optimal management strategies, including diagnostic testing, comorbidity screening, and both complementary and procedural treatment options. Recommendations and evidence grading based on the evidence available at the time of the review are provided. [ABSTRACT FROM AUTHOR]

Second-generation antihistamines are considered first-line agents in the treatment of chronic urticaria because of their safety and efficacy profile. Some patients require higher doses of H1 antihistamines alone or in combination with other classes of medications, including H2 antihistamines, leukotriene receptor antagonists, or first-generation H1 antihistamines. One major therapeutic advance has been omalizumab, a humanized monoclonal anti-immunoglobulin E that was recently approved by the US Food and Drug Administration for the treatment of chronic urticaria that is unresponsive to H1 antagonists. In addition, the second article in this continuing medical education series outlines several evidence-based alternative treatments for urticaria and the differences in recommendations between 2 major consensus groups (the European Academy of Allergy and Clinical Immunology/World Allergy Organization and the American Academy of Allergy, Asthma and Immunology/American College of Allergy, Asthma and Immunology Joint Task Force). [ABSTRACT FROM AUTHOR]

Urticaria is a common clinical condition presenting with wheals (hives), angioedema, or both. Urticaria has a complex pathogenesis, along with a high disease burden, a significant impact on quality of life, and high health care costs. The first article in this continuing medical education series covers the definition, classification, epidemiology, diagnosis, and work-up of urticaria, taking into account the recent literature and the best available evidence. [ABSTRACT FROM AUTHOR]

Background The genetic cause of primary immunodeficiency disease (PID) carries prognostic information. Objective We conducted a whole-genome sequencing study assessing a large proportion of the NIHR BioResource–Rare Diseases cohort. Methods In the predominantly European study population of principally sporadic unrelated PID cases (n = 846), a novel Bayesian method identified nuclear factor κB subunit 1 (NFKB1) as one of the genes most strongly associated with PID, and the association was explained by 16 novel heterozygous truncating, missense, and gene deletion variants. This accounted for 4% of common variable immunodeficiency (CVID) cases (n = 390) in the cohort. Amino acid substitutions predicted to be pathogenic were assessed by means of analysis of structural protein data. Immunophenotyping, immunoblotting, and ex vivo stimulation of lymphocytes determined the functional effects of these variants. Detailed clinical and pedigree information was collected for genotype-phenotype cosegregation analyses. Results Both sporadic and familial cases demonstrated evidence of the noninfective complications of CVID, including massive lymphadenopathy (24%), unexplained splenomegaly (48%), and autoimmune disease (48%), features prior studies correlated with worse clinical prognosis. Although partial penetrance of clinical symptoms was noted in certain pedigrees, all carriers have a deficiency in B-lymphocyte differentiation. Detailed assessment of B-lymphocyte numbers, phenotype, and function identifies the presence of an increased CD21low B-cell population. Combined with identification of the disease-causing variant, this distinguishes between healthy subjects, asymptomatic carriers, and clinically affected cases. Conclusion We show that heterozygous loss-of-function variants in NFKB1 are the most common known monogenic cause of CVID, which results in a temporally progressive defect in the formation of immunoglobulin-producing B cells. Graphical abstract [ABSTRACT FROM AUTHOR]

Multi-country outbreaks of foodborne bacterial disease present challenges in their detection, tracking, and notification. As food is increasingly distributed across borders, such outbreaks are becoming more common. This increases the need for high-resolution, accessible, and replicable isolate typing schemes. Here we evaluate a core genome multilocus typing (cgMLST) scheme for the high-resolution reproducible typing of Salmonella enterica ( S. enterica ) isolates, by its application to a large European outbreak of S. enterica serovar Enteritidis. This outbreak had been extensively characterised using single nucleotide polymorphism (SNP)-based approaches. The cgMLST analysis was congruent with the original SNP-based analysis, the epidemiological data, and whole genome MLST (wgMLST) analysis. Combination of the cgMLST and epidemiological data confirmed that the genetic diversity among the isolates predated the outbreak, and was likely present at the infection source. There was consequently no link between country of isolation and genetic diversity, but the cgMLST clusters were congruent with date of isolation. Furthermore, comparison with publicly available Enteritidis isolate data demonstrated that the cgMLST scheme presented is highly scalable, enabling outbreaks to be contextualised within the Salmonella genus. The cgMLST scheme is therefore shown to be a standardised and scalable typing method, which allows Salmonella outbreaks to be analysed and compared across laboratories and jurisdictions. [ABSTRACT FROM AUTHOR]

• In this manuscript, the SACNN-SOA is proposed for CKD-IoT-CC. • IoT devices, like wearable and sensors perform data acquisition process. • For CKD diagnostic model, the SACNN is applied. • SOA is used to optimize the self-attention convolutional neural network. • The proposed approach is implemented in python language its performance is analyzed. Nowadays, Internet of Things (IoT) and cloud platforms are broadly employed in numerous healthcare applications. Instead of using the limited storage and processing power found in mobile devices, the vast amount of data generated by internet of things devices in healthcare sector can be evaluated on a cloud platform. In this article, the Self-Attention Convolutional Neural Network optimized with Season Optimization Algorithm is proposed for Chronic Kidney Disease Diagnosis using IoT and cloud computing in Smart Medical Big Data health care system (SACNN-SOA-CKD-IoT-CC). IoT devices, like wearable and sensors perform data acquisition process. For chronic kidney disease (CKD) diagnostic model, the self-Attention convolutional neural network (SACNN) is applied. But, the SACNN not divulge any optimization systems adoption to calculate the optimal parameters and to make sure the exact categorization of Chronic Kidney Disease (CKD). Therefore, the season optimization algorithm (SOA) is used to optimize SACNN. The proposed approach is implemented in python language its performance is analyzed with performance metrices, like sensitivity, accuracy, recall, f-measure, specificity, network latency, scalability, response time, delay, and accuracy. The proposed SACNN-SOA-CKD-IoT-CC method achieves higher accuracy in CKD dataset of 15.66 %, 21.65 % and 9.64 %, lower error rate of 11.27 %, 8.35 %, and 21.06 % compared to the existing methods, like intelligent internet of things with cloud centric clinical decision support scheme for the prediction of CKD (LR-AME-CKD-IoT-CC), diagnostic prediction method for CKD in internet of things (MLP-SVM-CKD-IoT-CC) and ensemble of deep learning based clinical decision support system for CKD detection in medical internet of things environment (EDL-CDSS-CKD-IoT-CC). [ABSTRACT FROM AUTHOR]

The endometrium exhibits a unique physiology in its ability to cyclically respond to steroid hormones, resulting in morphologic changes that allow the pathologist's interpretation of proper endometrial function. Distinctive changes are also observed during times of physiologic hormonal changes, such as in pregnancy, or in pathologic and iatrogenic hormonal imbalances, as in certain functioning ovarian tumours and hormone therapy, respectively. The ubiquity of these states, in particular the widespread use of oral contraception, hormone replacement therapy, hormonal intrauterine devices, and nowadays frequent use of progestin as treatment for endometrial hyperplasia and carcinoma, requires that the pathologist be familiar with both the patient history as well as the histologic patterns specific to each entity in order to render an accurate, practical diagnosis for the clinician. Notably, some changes may mimic more worrisome lesions, and vigilance of these similarities and differential diagnosis is necessary in the evaluation of endometrial samples. [ABSTRACT FROM AUTHOR]

Although classic viral exanthems of childhood are well described, they are rarely differentiated in adults. Laboratory techniques for viral identification have advanced without substantial literature to suggest how a dermatologist ought to conduct a cost-effective and diagnostic viral panel. Certain clinical features such as petechiae, vesicles, and dusky macular or morbilliform exanthems point strongly toward a viral exanthem. Differentiation of drug and viral causes of morbilliform eruptions has proven difficult. It is possible that with further diagnostic refinement that unnecessary and fruitless workups of an exanthem and unneeded discontinuation of drugs can be avoided. We review viral exanthems based on clinical features and discuss the available and optimal laboratory techniques to assist the dermatologist in a targeted workup. [ABSTRACT FROM AUTHOR]

Vitiligo is a common skin disorder that results in depigmentation. With the appropriate management, many patients can minimize disease progression, attain repigmentation, and achieve cosmetically pleasing results. There are numerous medical and surgical treatments aimed at repigmentation; therapies for depigmentation are available for patients with recalcitrant or advanced disease. The use of cosmetics at all stages of treatment may be vital to the patient's quality of life. Understanding all the available options helps choose the appropriate treatment plan and tailor it to your patient. Part II of this two-part series on vitiligo discusses the indications for, evidence behind, and adverse effects associated with many of the therapies used for vitiligo. Both conventional medical and surgical options are discussed in addition to several alternative and promising new therapies. [ABSTRACT FROM AUTHOR]

Vitiligo is an acquired pigmentary disorder of unknown etiology that is clinically characterized by the development of white macules related to the selective loss of melanocytes. The prevalence of the disease is around 1% in the United States and in Europe, but ranges from less than 0.1% to greater than 8% worldwide. A recorded predominance of women may reflect their greater willingness to express concern about cosmetically relevant issues. Half of all patients develop the disease before 20 years of age. Onset at an advanced age occurs but is unusual, and should raise concerns about associated diseases, such as thyroid dysfunction, rheumatoid arthritis, diabetes mellitus, and alopecia areata. Generalized vitiligo is the most common clinical presentation and often involves the face and acral regions. The course of the disease is unpredictable and the response to treatment varies. Depigmentation may be the source of severe psychological distress, diminished quality of life, and increased risk of psychiatric morbidity. Part I of this two-part series describes the clinical presentation, histopathologic findings, and various hypotheses for the pathogenesis of vitiligo based on past and current research. [ABSTRACT FROM AUTHOR]

Background We set out to validate the accuracy of gravimetric quantification of blood loss during simulated major postpartum haemorrhage and to evaluate the technique in a consecutive cohort of women experiencing major postpartum haemorrhage. The study took part in a large UK delivery suite over a one-year period. All women who experienced major postpartum haemorrhage were eligible for inclusion. Methods For the validation exercise, in a simulated postpartum haemorrhage scenario using known volumes of artificial blood, the accuracy of gravimetric measurement was compared with visual estimation made by delivery suite staff. In the clinical observation study, the blood volume lost during postpartum haemorrhage was measured gravimetrically according to our routine institutional protocol and was correlated with fall in haemoglobin. The main outcome measure was the accuracy of gravimetric measurement of blood loss. Results Validation exercise: the mean percentage error of gravimetrically measured blood volume was 4.0 ± 2.7% compared to visually estimated blood volume with a mean percentage error of 34.7 ± 32.1%. Clinical observation study: 356 out of 6187 deliveries were identified as having major postpartum haemorrhage. The correlation coefficient between measured blood loss and corrected fall in haemoglobin for all patients was 0.77; correlation was stronger (0.80) for postpartum haemorrhage >1500 mL, and similar during routine and out-of-hours working. Conclusion The accuracy of the gravimetric method was confirmed in simulated postpartum haemorrhage. The clinical study shows that gravimetric measurement of blood loss is correlated with the fall in haemoglobin in postpartum haemorrhage where blood loss exceeds 1500 mL. The method is simple to perform, requires only basic equipment, and can be taught and used by all maternity services during major postpartum haemorrhage. [ABSTRACT FROM AUTHOR]

Background Although patients with medullary thyroid cancer are known to present with paraneoplastic hormone production, this is much less common with papillary thyroid cancer. Methods We present a patient with the cribriform morular variant of papillary thyroid cancer in association with familial adenomatous polyposis who developed a positive pregnancy test in the absence of known pregnancy. The patient had developed vaginal bleeding, and her laboratory testing was characterized by elevated serum human chorionic gonadotropin (β-hCG) concentrations, but negative qualitative urine results. After a thorough gynecological evaluation to exclude unexpected normal, ectopic, or molar pregnancy, we pursued an evaluation for other sources of β-hCG production. Results We showed that the elevated serum β-hCG concentrations were not the result of heterophile antibody interferences, and ultimately we proved that her recurrent tumor produced the ectopic β-hCG. This is the first report of β-hCG production by papillary thyroid cancer. Thus, the possibility of ectopic production of β-hCG by papillary thyroid cancer needs to be included in the differential diagnosis of elevated hCG concentration in the absence of pregnancy. Conclusions This study of an unusual paraneoplastic syndrome highlights the importance of investigating discrepancies in the clinical laboratory. [ABSTRACT FROM AUTHOR]

Background: Studies found associations between atopic dermatitis (AD) and various comorbidities.Objective: To appraise evidence of the association between AD and comorbidities among adults.Methods: Our multidisciplinary work group conducted a systematic review of the association between AD and selected comorbidities. We applied the Grading of Recommendations, Assessment, Development, and Evaluation for prognosis approach for assessing the certainty of the evidence, providing statements of association based on the available evidence.Results: Analysis of the evidence resulted in 32 statements. Clear evidence of the association of AD in adults and select allergic, atopic, immune-mediated mental health and bone health conditions and skin infections was identified. There is some evidence supporting an association between AD and substance use, attention deficit hyperactivity disorder, and elements of metabolic syndrome. Evidence suggests a small association with various cardiovascular conditions. The association between AD in adults and autism spectrum disorders, myocardial infarction, stroke, and metabolic syndrome is inconclusive.Limitations: This analysis is based on the best available evidence at the time it was conducted. This guideline does not make recommendations for screening or management of comorbidities in adults with AD.Conclusions: Clinicians should be aware of comorbidities associated with AD. Further research is needed to determine whether screening or management of comorbidities is beneficial for adults with AD. [ABSTRACT FROM AUTHOR]

Introduction Kaposi sarcoma (KS) is a rare disease that presents as 1 of 4 distinct clinicopathologic subtypes; however, it may present in populations outside those normally encountered. In such cases, it will be important to consider KS in the differential diagnosis, as it may mimic other neoplastic and non-neoplastic entities. Materials and methods We describe 2 cases of KS, 1 in a patient not clinically fitting any of the 4 subtypes and the other in a patient with atypical presentation in human immunodeficiency virus (HIV)-associated disease. The first is an 81-year-old African American (AA) woman with a history of KS of the leg, who presented with groin lymphadenopathy and the second is a 42-year-old AA man with a known history of HIV infection, no skin lesions, and new axillary lymphadenopathy. Results Fine-needle aspiration of the groin and axillary lymph node, respectively, showed atypical spindle cells in a lymphoplasmacytic background. The spindle cells were positive for human herpesvirus-8 on the cell block and subsequent lymph node excision. In patients with HIV infection, in addition to reactive and lymphoproliferative processes, KS should be considered. In the former case, the demographic of an elderly AA woman without immunosuppression would not cause concern for systemic KS, but for a metastatic tumor or lymphoma. Conclusions Cytology is a helpful tool in narrowing the differential diagnosis for spindle cell lesions. With a diagnosis of KS, clinicians would be able to query the clinical history for a possible etiology, such as HIV, and exclude the possibility of metastatic disease. [ABSTRACT FROM AUTHOR]

Abstract: The most challenging aspect for any clinician assessing a child presenting with bruising or bleeding and possible maltreatment is in deciphering whether the clinical signs are consistent with the stated mechanism. A thorough structured history from the child and relatives including a focused bleeding history is essential so that timely and appropriate investigations may be instigated. First stage investigations should include a full blood count and morphological examination of the blood film, a prothrombin time, activated partial thromboplastin time (aPTT), thrombin time and fibrinogen. First line investigations should include factor VIII and IX assays and a von Willebrand screen, as mild deficiencies may be masked by a normal aPTT. If these are normal or there is a clinical suspicion of a bleeding disorder further second-line tests should include additional factor assays, including factor XIII. If the von Willebrand screen is abnormal, further testing may be needed to further characterize to disease sub-type. The results of PFA-100 testing cannot be relied on to rule out von Willebrand disease or platelet function disorders. Platelet function should be assessed with platelet aggregation and nucleotide release studies in preference to PFA-100. Results must be interpreted in the context of the child's age and by a clinician experienced in paediatric haematology. [Copyright &y& Elsevier]

Abstract: The endometrium displays a unique physiology characterized by its cyclical response to steroid hormones, which results in morphological changes that contribute to a pathologist's interpretation of proper endometrial function. Distinctive changes are also observed during times of physiological hormonal shifts (such as during pregnancy), pathological hormonal imbalances (such as certain functioning ovarian tumours) and iatrogenic hormonal imbalances (such as hormone therapy). The ubiquity of these states, particularly in conjunction with the widespread use of oral contraceptives, hormone replacement therapy, and intrauterine devices, requires that the pathologist be familiar with both the complete patient history and the histologic patterns specific to each entity in order to obtain an accurate and practical diagnosis for the clinician. Furthermore, some endometrial changes may mimic more worrisome lesions, and vigilance is necessary to accurately distinguish among these histologic patterns when evaluating endometrial samples. [Copyright &y& Elsevier]

Background: Patients with multiple clinically dysplastic nevi are at increased risk for development of melanoma. However, the risk of melanoma arising in a histologically dysplastic nevus (HDN) is unknown.Objective: We sought to determine the rate of melanoma development in patients with HDNs that approached a microscopic border but were not re-excised.Methods: We performed a retrospective study of patients evaluated in our dermatology department from January 1, 1980, to December 31, 1989, who had a HDN that extended to within 0.2 mm of a microscopic punch, shave, or excision border and was not re-excised.Results: The average follow-up in our cohort of 115 patients was 17.4 years (range: 0.0-29.9): 82 patients (71.3%) were followed up for longer than 10 years, 78 (67.8%) longer than 15 years, and 73 (63.4%) had more than 20 years of follow-up; 66 of 115 nevi were mildly dysplastic, 42 moderately dysplastic, and 7 had severe dysplasia. No patient developed metastatic melanoma or melanoma at the site of removal of a HDN.Limitations: This was a retrospective study performed at 1 large academic medical center.Conclusion: During a long-term follow-up period, no patient developed melanoma at the site of an incompletely or narrowly removed HDN, providing evidence that routine re-excision of mildly or moderately dysplastic nevi may not be necessary. [ABSTRACT FROM AUTHOR]

There are no population-based incidence studies of hidradenitis suppurativa (HS). Using the medical record linkage system of the Rochester Epidemiology Project, we sought to determine the incidence of the disease, as well as other associations and characteristics, among HS patients diagnosed in Olmsted County, Minnesota, between 1968 and 2008. Incidence was estimated using the decennial census data for the county. Logistic regression models were fit to evaluate associations between patient characteristics and disease severity. A total of 268 incident cases were identified, with an overall annual age- and sex-adjusted incidence of 6.0 per 100,000. Age-adjusted incidence was significantly higher in women compared with men (8.2 (95% confidence interval (CI), 7.0-9.3) vs. 3.8 (95% CI, 3.0-4.7). The highest incidence was among young women aged 20-29 years (18.4 per 100,000). The incidence has risen over the past four decades, particularly among women. Women were more likely to have axillary and upper anterior torso involvement, whereas men were more likely to have perineal or perianal disease. In addition, 54.9% (140/255) patients were obese; 70.2% were current or former smokers; 42.9% carried a diagnosis of depression; 36.2% carried a diagnosis of acne; and 6% had pilonidal disease. Smoking and gender were significantly associated with more severe disease. [ABSTRACT FROM AUTHOR]

Abstract: The use of drug samples in a dermatology clinic is controversial. Drug samples are associated with influencing physician prescribing patterns often toward costlier drugs, increasing health care costs, increasing waste, inducing potential conflicts of interest, and decreasing the quality of patient education. On the other hand, they have the potential to help those in financial need, to improve adherence and convenience, and to expose patients to better drugs. Although some academic centers have banned drug samples altogether, many academic and private practices continue to distribute drug samples. Given the controversy of the topic, physicians who wish to distribute drug samples must do so in an ethical manner. We believe, when handled properly, drug sampling can be used in an ethical manner. [Copyright &y& Elsevier]

Abstract: Diseases of the periocular hair range from localized disease to systemic processes and may present challenging diagnostic questions. We present a comprehensive clinical guide to the evaluation and diagnosis of these disorders. Deficiencies in growth, excess production, changes in pigmentation, aberrant position, or abnormalities in form may affect this region’s hair. These range from benign to sight-, and even life-, threatening pathologies. [Copyright &y& Elsevier]

Background: The use of drug samples is a controversial issue in medicine. Objective: We sought to determine the pros and cons of drug sampling, and how drug sampling in general medicine differs from dermatology. Methods: Literature searches were conducted on PubMed, Google, and Yahoo!. Articles were found pertaining to drug sampling in general, and for dermatology specifically. Results: Numerous pros and cons for drug sampling were found in the literature search. We divided these by cost-related issues, such as the industry-wide cost of sampling and the use of sampling to assist the underinsured and poor, and quality of care issues, such as adherence, patient education, and safety considerations. Articles also suggested that dermatology may differ from general medicine as topical treatments have fewer side effects, are more complicated to use, and come in different vehicles. Limitations: We identified few studies specifically focused on issues relevant to sampling in dermatology. Conclusion: There are strong arguments for and against drug sampling involving both cost and quality of care issues. Dermatology-specific medications clearly differ from oral medications in several regards. We ultimately conclude that the benefits of drug sampling outweigh the risks, but give recommendations on how drug sampling can be done ethically and effectively, including limiting personal use, not selling samples, properly documenting sample release, teaching patients about proper use, teaching students and residents ethical use of samples, working with pharmaceutical representatives in an ethical manner, prescribing the drug that is best for the patient, and securing samples appropriately to prevent theft and misuse. [Copyright &y& Elsevier]

Abstract: Topical therapy is highly desirable in treating nail disorders due to its localized effects, which results in minimal adverse systemic events and possibly improved adherence. However, the effectiveness of topical therapies is limited by minimal drug permeability through the nail plate. Current research on nail permeation that focuses on altering the nail plate barrier by means of chemical treatments, penetration enhancers as well as physical and mechanical methods is reviewed. A new method of nail sampling is examined. Finally limitations of current ungual drug permeability studies are briefly discussed. [Copyright &y& Elsevier]

Background: Dermatophytes are responsible for a number of superficial fungal infections that affect millions worldwide. During microscopic observation a potassium hydroxide (KOH) fungal smear, various filamentous materials such as common textile fibers from socks can obfuscate proper discernment of dermatophytes. Objective: To differentiate dermatophytes from 9 common sock fibers. Methods: Nine different textile fiber samples were microscopically analyzed by using a KOH direct smear test; their defining structural features were compared and contrasted with those of dermatophytes. Results: Although there are several similarities, sock fibers tend to have a non-septate, uniform structure which differentiates them from dermatophytes. Sock fibers are also significantly larger than dermatophytes and can be viewed better at lower magnifications. Limitations: There is a lack of sock samples with 100% textile fiber composition. Also, fibers were examined in a clean setting, without the detritus that normally accompanies dermatophytes in a clinical setting. Conclusion: While textile fibers may be present in KOH preparations, their general appearance typically differs from that of dermatophytes; an observer who is familiar with these distinctions will be able to differentiate between the two. [Copyright &y& Elsevier]

Hidradenitis suppurativa, also known as acne inversa, is a chronic, often debilitating disease primarily affecting the axillae, perineum, and inframammary regions. Prevalence rates of up to 4% have been estimated. Our understanding of the disease has changed over time. It is now considered a disease of follicular occlusion rather than an inflammatory or infectious process of the apocrine glands. Clinically, the disease often presents with tender subcutaneous nodules beginning around puberty. The nodules may spontaneously rupture or coalesce, forming painful, deep dermal abscesses. Eventually, fibrosis and the formation of extensive sinus tracts may result. The location of the lesions may lead to social embarrassment and the failure to seek medical treatment. Therapies in the past have consisted of long-term antibiotics, antiandrogens, and surgery. New treatments like tumor necrosis factor–alfa inhibitors have given clinicians more options against this difficult disease. Learning objectives: After completing this learning activity, participants should be able to describe the clinical presentation, demographics, and prevalence of hidradenitis suppurativa, be familiar with current controversies regarding the pathogenesis of this complex, and be able to discuss potential treatments and their outcomes. [Copyright &y& Elsevier]

The concentration dependent (2.5–10% of dry weight/wet weight) protective effect of squid protein hydrolysate (SPH), extracted from Japanese flying squid and swordtip squid by protease treatment, on the state of water and denaturation of frozen lizardfish (Saurida wanieso) myofibrillar protein (Mf) were assessed on the basis of the amount of unfrozen water in Mf by differential scanning calorimetry and Mf Ca-ATPase inactivation during freezing at −25 °C for 90 days; the effects were compared with those of sodium glutamate. The Mf showed a higher amount of unfrozen water upon addition of SPH, regardless of level of addition and species differences, resulting in a markedly decreased inactivation of Mf Ca-ATPase throughout the freezing period. The Ca-ATPase activity in the Mf without SPH (control) dropped drastically from the beginning of the freezing. These findings suggest that the functional side chains of the peptides of SPH produce bound water in the Mf structure, which provides a structural alteration of the hydrate water that has a capacity to suppress the freeze-induced denaturation of Mf. An addition of 5.0–7.5% concentration of SPH is found to be suitable to increase the amount of unfrozen water and to prevent the freeze-induced denaturation of Mf. [Copyright &y& Elsevier]