Immune activation is the driving force behind the occurrence of AIDS and non-AIDS events, and is only partially reduced by antiretroviral therapy (ART). Soon after HIV infection, intestinal CD4+ T cells are depleted leading to epithelial gut damage and subsequent translocation of microbes and/or their products into systemic circulation. Bacteria and fungi are the two most abundant populations of the gut microbiome. Circulating lipopolysaccharide (LPS) and (1→3)-β-D-Glucan (βDG), major components of bacterial and fungal cell walls respectively, are measured as markers of microbial translocation in the context of compromised gut barriers. While LPS is a well-known inducer of innate immune activation, βDG is emerging as a significant source of monocyte and NK cell activation that contributes to immune dysfunction. Herein, we critically evaluated recent literature to untangle the respective roles of LPS and βDG in HIV-associated immune dysfunction. Furthermore, we appraised the relevance of LPS and βDG as biomarkers of disease progression and immune activation on ART. Understanding the consequences of elevated LPS and βDG on immune activation will provide insight into novel therapeutic strategies against the occurrence of AIDS and non-AIDS events.
Primary effusion lymphoma (pel) is a rare human herpesvirus 8 (hhv8)–related large B cell lymphoma with plasmablastic, immunoblastic, or anaplastic features that often carries a poor prognosis. This lymphoma occurs mainly in patients with hiv infection, most often with Epstein–Barr virus (ebv) co-infection, and usually presents as body cavity effusions or, less commonly, as extracavitary lesions without effusion (ec-pel). Chemotherapeutic treatment options are limited and require concurrent antiretroviral therapy (art).Here, we report the case of an adult patient with hiv infection and chronic hepatitis E virus (hev) co-infection who had low CD4 T cell recovery after years of art. The patient then developed a cutaneous ec-pel which rapidly regressed after 1 cycle of liposomal doxorubicin (ld) for his Kaposi sarcoma (ks) before treatment with chop chemotherapy. He had previously received numerous cycles of ld for cutaneous ks over 2 years.Because of the patient’s low CD4 T cell count, hev co-infection, and earlier unexpected remission of ec-pel before chop, the patient opted for a single trial of ld before other options. Surprisingly, he experienced a complete remission lasting 18 months. Subsequently, his ec-pel relapsed twice at 31 and at 41 months after the initial diagnosis. Upon recurrence, a similar single cycle of ld was given, which again induced remission. The patient today is in complete remission after a total of 4 ld infusions over 54 months.This patient represents a unique case of hiv-with-hhv8–related, ebv-negative ec-pel with chronic hev coinfection, in which rapid remission was achieved after a single cycle of ld, suggesting an antiviral response in addition to the chemotherapeutic effect.
Objectives The aim was to determine the effectiveness of the serum cryptococcal antigen (CrAg) test in the diagnosis of concurrent cryptococcal meningitis (CM) and as a predictor of mortality in HIV‐infected patients. Methods In this retrospective study, all HIV‐infected patients admitted to Shanghai Public Health Clinical Center from 1 January 2014 to 31 August 2016 were screened for serum CrAg using the latex agglutination test. Serum CrAg‐positive patients underwent lumbar puncture to confirm CM prior to the initiation of appropriate antifungal therapy and were followed up for at least 6 months. Results One hundred and four (7.1%) of the total of 1474 HIV‐infected patients screened were serum CrAg‐positive. CM was diagnosed in the majority of serum CrAg‐positive patients (71.3%; 67 of 94) and was confirmed in all (46 of 46) of the patients with headache or coma and in 43.8% (21 of 48) of patients without neurological symptoms. CrAg titres ≥ 1:1024 showed a sensitivity of 82.5% and a specificity of 86.7% for the diagnosis of concurrent CM (P < 0.001). The positive predictive value for CM in this population was 94.3%. A total of 13 serum CrAg‐positive patients [13.8%; 95% confidence interval (CI) 7.5–22.4%] died (11 as a result of CM and two others as a result of bacterial pneumonia) despite early antifungal treatment initiation. Serum CrAg titres ≥ 1:1024 predicted all‐cause mortality (hazard ratio 3.69; P = 0.03). Conclusions Serum CrAg titres ≥ 1:1024 not only were associated with concurrent CM but also predicted mortality. HIV‐infected patients with a positive serum CrAg test during screening should receive lumbar punctures regardless of symptoms to rule out CM and patients with serum CrAg titres ≥ 1:1024 should be offered immediate care.
Postsurgical adhesions are a common complication of surgical procedures that can lead to postoperative pain, bowel obstruction, infertility, as well as complications with future procedures. Several agents have been developed to prevent adhesion formation, such as barriers, anti‐inflammatory and fibrinolytic agents. The Food and Drug Administration (FDA) has approved the use of physical barrier agents, but they have been associated with conflicting clinical studies and controversy in the clinical utilization of anti‐adhesion barriers. In this review, we summarize the human anatomy of the peritoneum, the pathophysiology of adhesion formation, the current prevention agents, as well as the current research progress on adhesion prevention. The early cellular events starting with injured mesothelial cells and incorporating macrophage response have recently been found to be associated with adhesion formation. This may provide the key component for developing future adhesion prevention methods. The current use of physical barriers to separate tissues, such as Seprafilm®, composed of hyaluronic acid and carboxymethylcellulose, can only reduce the risk of adhesion formation at the end stage. Other anti‐inflammatory or fibrinolytic agents for preventing adhesions have only been studied within the context of current research models, which is limited by the lack of in‐vitro model systems as well as in‐depth study of in‐vivo models to evaluate the efficiency of anti‐adhesion agents. In addition, we explore emerging therapies, such as gene therapy and stem cell‐based approaches, that may offer new strategies for preventing adhesion formation. In conclusion, anti‐adhesion agents represent a promising approach for reducing the burden of adhesion‐related complications in surgical patients. Further research is needed to optimize their use and develop new therapies for this challenging clinical problem.
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