/pdf/nccn-clinical-practice-guidelines-in-oncology-hepatobiliary-1kpacqqvi8.pdf

NCCN clinical practice guidelines in oncology: hepatobiliary cancers.

Severe trauma continues to represent a global public health issue and mortality and morbidity in trauma patients remains substantial. A number of initiatives have aimed to provide guidance on the management of trauma patients. This document focuses on the management of major bleeding and coagulopathy following trauma and encourages adaptation of the guiding principles to each local situation and implementation within each institution. The pan-European, multidisciplinary Task Force for Advanced Bleeding Care in Trauma was founded in 2004 and included representatives of six relevant European professional societies. The group used a structured, evidence-based consensus approach to address scientific queries that served as the basis for each recommendation and supporting rationale. Expert opinion and current clinical practice were also considered, particularly in areas in which randomised clinical trials have not or cannot be performed. Existing recommendations were reconsidered and revised based on new scientific evidence and observed shifts in clinical practice; new recommendations were formulated to reflect current clinical concerns and areas in which new research data have been generated. This guideline represents the fourth edition of a document first published in 2007 and updated in 2010 and 2013. The guideline now recommends that patients be transferred directly to an appropriate trauma treatment centre and encourages use of a restricted volume replacement strategy during initial resuscitation. Best-practice use of blood products during further resuscitation continues to evolve and should be guided by a goal-directed strategy. The identification and management of patients pre-treated with anticoagulant agents continues to pose a real challenge, despite accumulating experience and awareness. The present guideline should be viewed as an educational aid to improve and standardise the care of the bleeding trauma patients across Europe and beyond. This document may also serve as a basis for local implementation. Furthermore, local quality and safety management systems need to be established to specifically assess key measures of bleeding control and outcome. A multidisciplinary approach and adherence to evidence-based guidance are key to improving patient outcomes. The implementation of locally adapted treatment algorithms should strive to achieve measureable improvements in patient outcome.

/pdf/the-european-guideline-on-management-of-major-bleeding-and-50g3zxrre8.pdf

The European guideline on management of major bleeding and coagulopathy following trauma: fourth edition

Introduction: Evidence-based recommendations are needed to guide the acute management of the bleeding trauma patient. When these recommendations are implemented patient outcomes may be improved. Methods: The multidisciplinary Task Force for Advanced Bleeding Care in Trauma was formed in 2005 with the aim of developing a guideline for the management of bleeding following severe injury. This document represents an updated version of the guideline published by the group in 2007 and updated in 2010. Recommendations were formulated using a nominal group process, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence and based on a systematic review of published literature. Results: Key changes encompassed in this version of the guideline include new recommendations on the appropriate use of vasopressors and inotropic agents, and reflect an awareness of the growing number of patients in the population at large treated with antiplatelet agents and/or oral anticoagulants. The current guideline also includes recommendations and a discussion of thromboprophylactic strategies for all patients following traumatic injury. The most significant addition is a new section that discusses the need for every institution to develop, implement and adhere to an evidence-based clinical protocol to manage traumatically injured patients. The remaining recommendations have been re-evaluated and graded based on literature published since the last edition of the guideline. Consideration was also given to changes in clinical practice that have taken place during this time period as a result of both new evidence and changes in the general availability of relevant agents and technologies. Conclusions: A comprehensive, multidisciplinary approach to trauma care and mechanisms with which to ensure that established protocols are consistently implemented will ensure a uniform and high standard of care across Europe and beyond.

/pdf/management-of-bleeding-and-coagulopathy-following-major-127uh3smia.pdf

Management of bleeding and coagulopathy following major trauma: an updated European guideline

IntroductionEvidence-based recommendations are needed to guide the acute management of the bleeding trauma patient. When these recommendations are implemented patient outcomes may be improved.MethodsThe multidisciplinary Task Force for Advanced Bleeding Care in Trauma was formed in 2005 with the aim of developing a guideline for the management of bleeding following severe injury. This document represents an updated version of the guideline published by the group in 2007 and updated in 2010. Recommendations were formulated using a nominal group process, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence and based on a systematic review of published literature.ResultsKey changes encompassed in this version of the guideline include new recommendations on the appropriate use of vasopressors and inotropic agents, and reflect an awareness of the growing number of patients in the population at large treated with antiplatelet agents and/or oral anticoagulants. The current guideline also includes recommendations and a discussion of thromboprophylactic strategies for all patients following traumatic injury. The most significant addition is a new section that discusses the need for every institution to develop, implement and adhere to an evidence-based clinical protocol to manage traumatically injured patients. The remaining recommendations have been re-evaluated and graded based on literature published since the last edition of the guideline. Consideration was also given to changes in clinical practice that have taken place during this time period as a result of both new evidence and changes in the general availability of relevant agents and technologies.ConclusionsA comprehensive, multidisciplinary approach to trauma care and mechanisms with which to ensure that established protocols are consistently implemented will ensure a uniform and high standard of care across Europe and beyond.http://ccforum.com/content/17/4/442

This Provisional PDF corresponds to the article as it appeared upon acceptance. Copyedited and fully formatted PDF and full text (HTML) versions will be made available soon. Management of bleeding and coagulopathy following major trauma: an updated European guideline

Introduction: Evidence-based recommendations are needed to guide the acute management of the bleeding trauma patient, which when implemented may improve patient outcomes. Methods: The multidisciplinary Task Force for Advanced Bleeding Care in Trauma was formed in 2005 with the aim of developing a guideline for the management of bleeding following severe injury. This document presents an updated version of the guideline published by the group in 2007. Recommendations were formulated using a nominal group process, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence and based on a systematic review of published literature. Results: Key changes encompassed in this version of the guideline include new recommendations on coagulation support and monitoring and the appropriate use of local haemostatic measures, tourniquets, calcium and desmopressin in the bleeding trauma patient. The remaining recommendations have been reevaluated and graded based on literature published since the last edition of the guideline. Consideration was also given to changes in clinical practice that have taken place during this time period as a result of both new evidence and changes in the general availability of relevant agents and technologies. Conclusions: This guideline provides an evidence-based multidisciplinary approach to the management of critically injured bleeding trauma patients.

/pdf/management-of-bleeding-following-major-trauma-an-updated-59vf8dn6w1.pdf

Management of bleeding following major trauma: an updated European guideline

Background: Cutaneous disease is common in patients infected with HIV-1. Objective: The aim of our study was to identify cutaneous markers associated with HIV-1 infection and disease progression as measured by Walter Reed (WR) stage. Methods: For 42 months we have observed 912 HIV-1-positive patients in all WR stages. All patients had an extensive past and present medical history taken as well as a complete physical examination, periodic visits, and appropriate diagnostic procedures. Results: Increasing dryness of the skin and seborrheic dermatitis are early findings in a large percentage of patients in WR stage 1; the occurrence and severity of both conditions increase with disease progression. Tinea infections, condylomata acuminata, and Verrucae are seen early, but with disease progression, although there is no clear increase in occurrence, these infections become more diffuse and resistant to treatment. Flares in acne vulgaris and folliculitis show a peak occurrence in early and mid-stage disease with a decreased occurrence in late-stage disease. Herpes simplex infections, oral candidiasis, molluscum contagiosum, Staphylococcus aureus infections, and oral hairy leukoplakia show a marked increase in occurrence with advanced disease. Conditions that have a statistically significant association with disease progression as measured by a change in stage include drug eruptions, seborrheic dermatitis, oral candidiasis, oral hairy leukoplakia, molluscum contagiosum, herpes zoster, and hyperpigmentation (nail, oral, skin). Conclusion: The most frequent and persistent cutaneous disorders were asteatosis (with or without asteatotic eczema) and seborrheic dermatitis. Conditions that were associated with a change in WR stage include drug eruptions, seborrheic dermatitis, oral candidiasis, oral hairy leukoplakia, molluscum contagiosum, herpes zoster, and hyperpigmentation. In addition to Kaposi's sarcoma, patients with HIV-1 disease have an increased potential for the development of both cutaneous epithelial and probably melanocytic malignancies. Epithelial tumors were seen in patients in all stages of disease.

Cutaneous findings in HIV-1-positive patients: A 42-month prospective study

Background: Desmoplastic malignant melanoma (DMM) is an uncommon variant of malignant melanoma and often is difficult to diagnose. Because of the relative rarity of this tumor, it has not been well studied and controversy remains concerning its biologic potential. Objective: We compared survival rates of DMM with those of other malignant melanomas and determined what clinical and/or histologic features, if any, correlated with survival. Methods: The files of the Armed Forces Institute of Pathology were searched for cases of DMM or related tumors with adequate material for further histologic and immunohistochemical evaluation. Follow-up on each patient was requested from the pathologist, clinician, and/or the patient. The follow-up was correlated with the histologic findings in each case. The relationship of histologic features to disease-free survival was evaluated. Results: Adequate material for evaluation was available in 128 cases. The overall histologic features were similar to those previously reported. Immunohistochemical studies showed that all lesions were negative for HMB-45, a marker for premelanosomes. Factors that correlated with survival included tumor location, sex, tumor depth, and the presence of stromal mucin. The 5-year disease-free survival rate was 68% for all cases and 61% for lesions more than 4 mm deep. Conclusion: With a 5-year disease-free survival rate of 61%, DMM has a significantly better prognosis than other melanomas that have a 5-year disease-free survival rates of 40% to 41%. This may be related to neural differentiation of these tumors.

Desmoplastic malignant melanoma

Majocchi's granuloma (nodular granulomatous perifolliculitis) is a well recognized but uncommon infection of dermal and subcutaneous tissue by fungal organisms (dermatophytes) usually limited to the superficial epidermis. The organism usually associated with Majocchi's granuloma is Trichophyton rubrum; however, other dermatophytes including T. mentagrophytes (variety granulosum), T. epilans, T. violaceum, M. audouinii, M. gypseum, M. ferrugineum, and M. canis may be the causative agent. A review of 17 cases revealed not only the variety of possible organisms but also a marked variation from the usual hyphal forms. The morphologic variations including yeast forms, bizarre hyphae, mucinous coatings, and the Splendore-Hoeppeli phenomenon may be factors which allow the dermatophytes to persist and grow in an abnormal location. Also, there is evidence that Majocchi's granuloma may occur in two distinct groups of patients.

Majocchi's granuloma.

N-methyl-2,2'-dichlorodiethylamine (HN2)is a topical chemotherapeutic agent used as therapy for cutaneous T-cell lymphomas (CTCL). Di(2-chloroethyl)sulfide (SM), and less often HN2, have been used as chemical weapons, with the skin being a principle target. The mechanisms by which these chemicals produce their therapeutic and toxic effects in skin, however, are not clearly defined. We exposed human skin explants to two doses of HN2 and SM. At 18 hours after exposure, histopathologic features were compared. In addition, immunohistochemical markers to basement membrane proteins were used to evaluate the effects of both chemicals on the basement membrane zone. Gross vesication was not seen. Pyknotic nuclei with or without dyskeratotic changes within epidermal keratinocytes were present at both doses. These changes varied more between skin specimens than they did between doses. Ballooning degeneration was more marked after SM exposures. Diffuse dermal-epidermal separation was present only at high-dose exposures and did not appear to correlate with the degree of changes locally in the overlying epidermis. Antibodies to laminin-5 showed decreased immunoreactivity after exposure to HN2 and SM. Immunoreactivity for laminin- was decreased to a lesser extent, and immunoreactivity for collagen IV and VII was unchanged. HN2 and SM produce similar histopathologic and immunohistochemical features after cutaneous exposure. These features suggest that part of mechanism of action of HN2 and SM is a direct effect on the basement membrane zone. Understanding the effects of HN2 and SM separate from their effect on DNA may be important in designing therapies and in advancing our understanding of the pathophysiologic changes induced by these chemicals when delivered topically.

Histopathologic and immunohistochemical features in human skin after exposure to nitrogen and sulfur mustard.

Drug reactions are common in HIV-1 disease, with the incidence having been reported to increase with increasing stage and with CD4+ T-cell counts below 200/microliters. However, there have been numerous reports of patients in which rechallenge, dosing changes or continued therapy have resulted in no recurrence or else clearing of the eruption. We followed 974 HIV-1-positive patients for 46 months as a part of a military study of HIV-1 disease. Within this group there were a total of 283 drug eruptions, with cutaneous manifestations in 201 patients in which clinical characteristics were noted and 86 patients in which cutaneous biopsies were performed. Serological evidence of reactivation or acute Epstein-Barr virus (EBV) or cytomegalovirus (CMV) infections were also noted, as well as peripheral eosinophilia. The incidence of drug eruptions significantly increased with increasing Walter Reed stage and decreasing CD4 counts and CD4/CD8 ratio, as well as with increasing age and in patients with increased numbers of other dermatological diagnoses. In addition, white patients had significantly more drug eruptions than did black. Serological or culture evidence of acute or reactivated EBV or CMV was significantly increased in patients with drug eruptions. The majority of the eruptions were maculopapular or morbilliform with a predominantly perivascular mononuclear cell infiltrate. HIV-1 positive patients have an increased incidence of drug reactions, the incidence having been reported to increase in patients with less than 200 CD4+ T cells/microliter. However, at very low T4 counts, especially those less than 25/microliter, and at a CD4/CD8 ratio of less than 0.10, the probability of reactions to trimethoprim-sulphamethoxazole (TMP-SMZ) is decreased in late-stage HIV-1 patients. Maculopapular or morbilliform eruptions are the most common clinical presentations, often accompanied by one or more of the following: fever, arthralgias, eosinophilia, and serum transaminase elevation. Histologically the majority of these eruptions show a perivascular mononuclear cell infiltrate, sometimes with focal interface changes and apoptotic, necrotic cells within the epidermis. Acute hypersensitivity reactions and toxic epidermal necrolysis (TEN) or Stevens-Johnson's syndrome (SJS) with diffuse epidermal apoptosis and necrosis have also been less commonly described. In a study of cutaneous manifestations in an HIV-1 positive military population, drug reactions were evaluated in terms of clinical features, histopathology, demographic features and laboratory findings.

Kathleen J. Smith

Papers

Cutaneous findings in HIV-1-positive patients: A 42-month prospective study

Desmoplastic malignant melanoma

Majocchi's granuloma.

Histopathologic and immunohistochemical features in human skin after exposure to nitrogen and sulfur mustard.

Increased drug reactions in HIV-1-positive patients : a possible explanation based on patterns of immune dysregulation seen in HIV-1 disease