By E. Ramirez. Coleman College.

    In a study of 382 febrile HIV+ patients in San Francisco apcalis sx 20mg otc, Bartonella was found to be the causative organism in 18% (Koehler 2003) apcalis sx 20 mg for sale. Bacillary angiomatosis remains a significant differential diagnosis in all cases with skin lesions of unknown etiology. The pseudoneoplastic, vascular skin proliferation is quite often clinically and histologically mistaken for Kaposi’s sarcoma or heman- gioma. The vascular nodules or tumors may be isolated, but are usually multiple and reminiscent of fresh Kaposi’s sarcoma, with cherry red or purple nodules. One quarter of the cases may have bone involvement with painful osteolytic foci (AP elevation). Here, the skin lesions sometimes resemble dry hyperkeratotic changes such as those seen in psoriasis. In a collection of 21 cases, 19 patients had skin, 5 bone and 4 liver involvement (Plettenberg 2000). Mani- festations in lymph nodes, muscle, CNS, eye, gingiva and gastrointestinal tract have also been reported. The gram-negative bacteria are only visible on biopsy samples stained with Warthin-Starry silver stain. If this stain method is not applied, then bacillary angiomatosis will not be found. Moreover, pathologists should be informed of the suspected diagnosis, as the Warthin-Starry silver stain is not routinely performed. Reference labs should be contacted for further diagnostic details. Treatment of bacillary angiomatosis is with erythromycin (at least four weeks with 500 mg QID) or clarithromycin. Relapses are common, which is why some physi- cians favor therapy for at least three months. Supposedly effective, doxycyclin is the 404 AIDS therapy of choice for CNS involvement. Since transmission is generally via cats, US guidelines recommend not having cats as pets. Preferably, cats should be healthy and older than one year; and scratches should be avoided. Bacillary angiomatosis: a newly characterized, pseudoneoplastic, infectious, cutaneous vascular disorder. Molecular epidemiology of bartonella infections in patients with bacil- lary angiomatosis-peliosis. Prevalence of Bartonella infection among hiv-infected patients with fever. LeBoit PE, Berger TG, Egbert BM, Beckstead JH, Yen TSB, Stoler MH. Bacillary angiomatosis: the histopathology and differential diagnosis of a pseudoneoplastic infection in patients with HIV disease. Komplett im Plettenberg A, Lorenzen T, Burtsche BT, et al. Bacillary angiomatosis in HIV-infected patients—an epidemiologi- cal and clinical study. Stoler MH, Bonfiglio TA, Steigbigel RB, et al: An atypical subcutaneous infection associated with AIDS. Histoplasmosis Histoplasma capsulatum is a dimorphic mold, found largely in moist soil and without a capsule despite its name. The Southern and Midwestern of regions of the US as well as Central America and Africa are endemic areas. Even in the HAART era, morbidity and mortality due to histoplasmosis remains a public heatlh problem in low-income and high-income countries (Review: Adenis 2014). In HIV patients with impaired immunity (85% have less than 100 CD4 T cells/µl), infection leads to an acute, life- threatening disease with dry cough, fever, dyspnea and malaise (Gutierrez 2005, Mora 2008). Miliary TB and PCP are important differential diagnoses. Disseminated courses of disease may also occur, in which the fungus can be detected in bone marrow or by liver biopsy (Albrecht 1994). Skin ulcerations, oropharynx or CNS involvement may also occur (Scheinfeld 2003, Wheat 2005, Antonello 2011).

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    Developing macrophages as a biomarker Further studies are required to establish IHC for macrophages as a Macrophages and outcomes in specific populations biomarker that can be used prospectively to risk-stratify patients The population used by Steidl et al15 to establish the relationship (Figure 2) discount apcalis sx 20mg online. Specifically discount 20 mg apcalis sx with amex, an assay needs to be defined including a between macrophages and outcomes was dominated by the NS suitable antibody, staining methods, scoring methodologies, and subtype, with only 7% of the cases being the MC subtype. In total, thresholds that identify groups at different risk. Ultimately, to 16% of the cases were EBV (Christian Steidl, BC Cancer Agency, demonstrate the robustness and portability of the assay, it then needs Vancouver, Canada, April 2014, personal communication of unpub- to be externally validated in another laboratory in cohorts of patients lished data). The subsequent IHC studies have also treated CHL as a independently from those in which the assay was trained. Although the prognostic significance of Antibody characteristics. The IHC studies published to date used macrophages in adult patients with the NS subtype is well sup- a variety of different antibodies to stain for macrophages and, in ported, the relationship between macrophages and outcomes in doing so, have identified their performance characteristics. In the GEP study by Chetaille et al,6 the visual estimation method—a finding confirmed by Klein et al. Accordingly, antibodies against with EBV HRS cells from those that were EBV. In all studies that CD68 are known to recognize not only macrophages, but also other have examined the relationship, EBV cases have a significantly cells potentially found in the TME, such as myeloid cells, fibro- higher number of CD68 20,25,31 and CD163 20,25 cells in the TME. Interobserver agreement is improved using antibodies to larger cohort of EBV cases, including limited and advanced stage, CD163,29,32 which are more specific for macrophages than either the neither CD68 nor CD163 was associated with outcomes. Given the strong association to CD163 reportedly staining alternatively activated (M2) macro- between EBV and the MC subtype, it is not surprising that biopsies phages, whereas antibodies to CD68 stain all macrophage popula- of the MC subtype consistently show higher numbers of macro- tions. When antibodies to CD68 and CD163 have both been used, phages, a finding dating back to Ree and Kadin’s study and some studies have noted discrepancies between their associations confirmed using antibodies to both CD68 and CD163. Sanchez-Espiridion et al24 observed an association that the MC subtype is not, in and of itself, associated with poor between increased CD68 (KP1 clone)-stained cells and DSS in a outcome, this raises doubt as to whether macrophages have prognos- Spanish cohort, but no association was seen using an antibody to tic power in this subtype. In contrast, Zaki et al21 and Klein et al29 only saw an association between CD163 and outcome. Two studies, by Barros et al38 and Gupta et al,39 have investigated the relationship between macrophages and out- Scoring methods and thresholds. Beyond the visual estimation come in pediatric CHL, in 100 and 96 patients, respectively. Neither method, several scoring methodologies have been used, ranging study found any significant relationship between CD68 IHC and from cell counting19,21,34 to computer-assisted methods of point outcomes, although Barros et al38 found that CD163 IHC was counting20,24 and computer-assisted image analysis. Gupta et al39 did not observe an association between CD163 tory agreement, this improvement comes at the expense of either and outcomes, but did not determine the EBV status of the HRS being labor intensive or requiring specialized equipment. Steidl et al15 reported that having very wide range of suggested thresholds for separating patients into 5% CD68 cells in the diagnostic biopsy was associated with low- and high-risk populations, ranging from 0. Only one study, Casulo et al,40 has examined the stage CHL patients uniformly treated with ABVD enriched for prognostic significance of macrophages in the biopsy obtained at treatment failure. A weighted analysis approach was used to correct relapse in CHL. In a cohort of 81 patients with relapsed or refractory for the enrichment, allowing unbiased estimates of the model’s CHL undergoing salvage treatment before ASCT, increased CD68 performance. The assay identified a high-risk group with signifi- macrophages were associated with inferior OS in a univariate cantly worse FFS and OS in the validation cohort independently of analysis. When they considered the 70 patients who received ASCT, the International Prognostic Factors Project score, age 45 years, those that had 30% CD68 macrophages had inferior event-free and CD68 IHC. The relatively low numbers of patients with the MC survival and OS. A fundamentally different approach from that pursued with the macrophage studies is seen with the development of prognostic Concluding remarks gene expression-based models. In these studies, the investigators In the years since the discovery of the relationship between used the combined prognostic power of individual genes and tumor-associated macrophages and outcomes after upfront ABVD, signatures with the express purpose of producing multigene biomark- a body of literature has accumulated validating and giving texture to ers for risk stratification. This requires the transition of gene this biological relationship. The precise biology underlying the expression signatures derived from previous studies to technology association remains unclear and forthcoming studies are anticipated platforms suitable for the reliable quantitation of gene expression in to determine whether macrophages represent direct participants in the highly fragmented RNA extracted from routinely produced the chemoresistant phenotype or if they are a surrogate for genetic formalin-fixed paraffin-embedded tissue (FFPET) (Figure 2).

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