Severe ischemic cytomegalovirus proctocolitis with multipleperforation

AbstractCytomegalovirus (CMV) typically causes gastrointestinal infections in immunocompetent patients. Colonic perforationssecondary to CMV are exceeding rare. We describe a 88-year-old male presenting with a week-long history of intractableabdominal discomfort, bloating, nausea and diarrhea. Flexible sigmoidoscopy revealed significant ulceration with yellowishslough. Emergency surgery was performed subsequently in view of multiple perforations in the rectosigmoid junction. CMVgastrointestinal infections demonstrated an ischemic process secondary to vasculitis, which accelerated the pathway to colonicperforation. CMV gastrointestinal infection should be considered as a differential diagnosis in patients with colonoscopyfindings similar to ischemic colitis and Clostridium difficile infections

Continuing education for pathology laboratory technologists: a needs analysis in a Singapore teaching hospital

10.1136/jcp.2006.045195Journal of Clinical Pathology60111273-1276JCPA

Multiphoton Microscopic Study of the Renal Cell Carcinoma Pseudocapsule: Implications for Tumour Enucleation

10.1016/j.urology.2020.06.064UROLOGY144249-25

Multiple Myeloma-Associated Light Chain Amyloidosis and a Proposed Approach to Monoclonal Immunoglobulin-Associated Renal Disease

10.1159/000508785Case Reports in Nephrology and Dialysis10395-10

Multi-photon microscopy for the evaluation of interstitial fibrosis in extended criteria donor kidneys: A proof-of-concept study

10.1111/ctr.14717CLINICAL TRANSPLANTATIO

Tocilizumab Induces IL-10-Mediated Immune Tolerance in Invasive Candidiasis

The existence of a hyperinflammatory state has been observed in patients with invasive fungal infections (IFI). It is being postulated whether morbidity from IFI may, in part, be a consequence of an unnecessarily prolonged or exaggerated proinflammatory immune response including interleukin 6 (IL-6) post-infection, in a host with dysregulated or compromised immunity. This, in turn, induces collateral host injury at the tissue and organ level, leading to adverse outcomes. Tocilizumab has become widely used as an immunomodulator in the treatment of inflammatory conditions. Here, we evaluated the use of tocilizumab to curb post-infective inflammatory flare in the setting of an in-vivo mouse model for invasive candidiasis. Following Candida infection, the tocilizumab-treated mice showed improved short-term survival compared with the saline-treated control mice. There was a reduced inflammatory response mounted by the host, coupled with reduced IL-6 but increased IL-10 levels. TNF-α and IFN-γ responses were not affected. Tocilizumab facilitated immune tolerance by selectively inducing IL-10, producing CD8α+ conventional dendritic cells (DCs) and peripheral T-regulatory cells, over CD11b+ conventional DCs and plasmacytoid DCs. We demonstrate here the sequelae from immunomodulatory manipulation and the basis whereby the use of monoclonal antibodies may be further explored in IFI

TLR7 protein expression in mild and severe lupus-prone models is regulated in a leukocyte, genetic, and IRAK4 dependent manner

The global increase in autoimmunity, together with the emerging autoimmune-related side effects of cancer immunotherapy, have furthered a need for understanding of immune tolerance and activation. Systemic lupus erythematosus (SLE) is the archetypical autoimmune disease, affecting multiple organs, and tissues. Studying SLE creates knowledge relevant not just for autoimmunity, but the immune system in general. Murine models and patient studies have provided increasing evidence for the innate immune toll like receptor-7 (TLR7) in disease initiation and progression. Here, we demonstrated that the kinase activity of the TLR7-downstream signaling molecule, interleukin-1 receptor associated kinase 4 (IRAK4), is essential for mild and severe autoimmune traits of the Sle1 and Sle1-TLR7 transgenic (Sle1Tg7) murine models, respectively. Elimination of IRAK4 signaling prevented all pathological traits associated with murine lupus, including splenomegaly with leukocyte expansion, detectable circulating antinuclear antibodies and glomerulonephritis, in both Sle1 and Sle1Tg7 mice. The expansion of germinal center B cells and increased effector memory T cell phenotypes that are typical of lupus-prone strains, were also prevented with IRAK4 kinase elimination. Analysis of renal leukocyte infiltrates confirmed our earlier findings of an expanded conventional dendritic cell (cDC) within the kidneys of nephritic mice, and this was prevented with IRAK4 kinase elimination. Analysis of TLR7 at the protein level revealed that the expression in immune cells is dependent on the TLR7-transgene itself and/or autoimmune disease factors in a cell-specific manner. Increased TLR7 protein expression in renal macrophages and cDCs correlated with disease parameters such as blood urea nitrogen (BUN) levels and the frequency of leukocytes infiltrating the kidney. These findings suggest that controlling the level of TLR7 or downstream signaling within myeloid populations may prevent chronic inflammation and severe nephritis.ASTAR (Agency for Sci., Tech. and Research, S’pore)Published versio

Predictive value of p53 and pRb expression in superficial bladder cancer patients treated with BCG and interferon-alpha

10.1002/cncr.22503Cancer10961097-110