Epidemiological link between obesity,type 2 diabetes mellitus and cancer

There exists a complex interaction between obesity, type 2 diabetes mellitus (T2DM) and cancer, and an increase in the incidence of cancer is expected with the growing obesity-diabetes pandemic. The association of cancer with diabetes mellitus and obesity appears to be site-specific, the highest risk being for post-menopausal breast cancer, endometrial cancer, and colorectal cancer. Moreover, there is worsening of hyperglycaemia with the onset of cancer, evidencing a bi-directional link between cancer and diabetes mellitus and the need for monitoring for diabetes in cancer survivors. In this review, we look at the epidemiological evidence from observational studies and Mendelian randomization studies linking obesity, diabetes, and cancer, as well as the complex pathophysiological mechanisms involved, including insulin resistance with associated hyperinsulinaemia, the effect of chronic low-grade inflammation, and the effect of various adipokines that are associated with obesity and T2DM. Additionally, we describe the novel therapeutic strategies, based on their role on the discrete pathophysiological mechanisms involved in the tumourigenesis.     

Enolase 1 of Candida albicans binds human CD4+ T cells and modulates naïve and memory responses

To obtain a better understanding of the biology behind life-threatening fungal infections caused by Candida albicans, we recently conducted an in silico screening for fungal and host protein interaction partners. We report here that the extracellular domain of human CD4 binds to the moonlighting protein enolase 1 (Eno1) of C. albicans as predicted bioinformatically. By using different anti-CD4 monoclonal antibodies, we determined that C. albicans Eno1 (CaEno1) primarily binds to the extracellular domain 3 of CD4. Functionally, we observed that CaEno1 binding to CD4 activated lymphocyte-specific protein tyrosine kinase (LCK), which was also the case for anti-CD4 monoclonal antibodies tested in parallel. CaEno1 binding to naïve human CD4⁺ T cells skewed cytokine secretion toward a Th2 profile indicative of poor fungal control. Moreover, CaEno1 inhibited human memory CD4⁺ T-cell recall responses. Therapeutically, CD4⁺ T cells transduced with a p41/Crf1-specific T-cell receptor developed for adoptive T-cell therapy were not inhibited by CaEno1 in vitro. Together, the interaction of human CD4⁺ T cells with CaEno1 modulated host CD4⁺ T-cell responses in favor of the fungus. Thus, CaEno1 mediates not only immune evasion through its interference with complement regulators but also through the direct modulation of CD4⁺ T-cell responses.     

Cranial melioidosis with extradural extension after a fall in the bathroom

A 32-year-old diabetic male, with a past history of head injury and seizures, presented with a painful swelling over his forehead present for the past three months. Cranial MRI demonstrated the presence of a scalp collection with extradural extension through a bony defect. Biopsy from the area showed caseating necrosis suggestive of tuberculosis. Although the patient failed to return for initiation of anti-tubercular therapy for the next 11 months, the swelling did not progress, and there were no constitutional symptoms. The indolent nature of the swelling prompted re-evaluation and delayed cultures of pus from the collection grew Burkholderia pseudomallei.     

HIV–tuberculosis co–infection in an Indian scenario: The role of associated evidence of immunosuppression

ObjectiveTo determine the relationship between tuberculosis and the degree of immunosuppression as determined by CD4 count. The impact of immunosuppression on the severity of tuberculosis was also studied.MethodsA retrospective analysis was performed in patients newly diagnosed with HIV infection and antiretroviral therapy (ART)-naive patients with known HIV seropositivity. All patients were diagnosed with active tuberculosis between January 2008 and December 2010, based on review of their medical records. Patients on chemoprophylaxis for opportunistic infection were excluded. Pattern and severity of tuberculosis, associated stigmata of immunosuppression, and CD4 counts were noted.ResultsOf 140 patients satisfying the inclusion criteria, 52 had mild tuberculosis with no other evidence of immunosuppression, 52 had tuberculosis of variable severity with associated evidence of immunosuppression, and 36 had severe tuberculosis with no other evidence of immunosuppression. The CD4 count was highest in the first group [(109.2±99.9) cells/μL] and least in the second group [(58.4±39.8) cells/μL], and the difference was statistically significant (P=0.004). No statistical difference was observed in the CD4 count between those with mild tuberculosis and those with severe tuberculosis.ConclusionsIn developing countries with a high prevalence of tuberculosis in the general population, the possibility of incidental tuberculosis in patients with HIV should always be considered. CD4 count does not appear to influence the severity of tuberculosis. The presence of concomitant evidence of immunosuppression in the form of category B and C conditions is indicative of underlying immunosuppression and associated with a significantly lower CD4 count.     

Photoacoustic dual-scan mammoscope: results from 38 patients

We have developed a photoacoustics-based imaging system, the dual-scan mammoscope (DSM), that combines optical contrasts with acoustic detection, to obtain the angiographic features in human breast. In this study, we investigated whether the system can differentiate malignant tumor and healthy breast. We have imaged 38 patients with various tumor types and compared results of tumor-bearing breast with healthy breast for each patient. We also compared the photoacoustic and ultrasound imaging results with clinical US. Vascular features in and around the tumor mass were visualized. We found that tumor-bearing breast contained vessels of larger caliber and exhibited stronger variations in the background signals than those in the contralateral healthy breasts. Preliminary data on photoacoustic and ultrasound images also indicate that the technique has potential in differentiating different tumor types. Overall, our results indicate that combining photoacoustic and ultrasound images can improve breast cancer screening.     

Pharmacomechanical thrombolysis of acute and chronic symptomatic deep vein thrombosis: a systematic review of literature

Pharmacomechanical thrombolysis (PMT) is an emerging treatment option for symptomatic deep vein thrombosis (DVT). This may obviate the need for systemic or catheter-directed thrombolysis. PubMed, EMBASE, and Cochrane database search of PMT in acute and chronic symptomatic DVT was undertaken. Baseline demographic and clinical characteristics, procedural details, DVT characteristics, and procedural and clinical outcomes are presented. A total of 8 case series (n = 2528; 1998-2009) qualified for inclusion. Lower extremity symptomatic DVTs constituted the majority of the cases (>80%). Both acute (<14 days) and chronic (>14 days) DVTs were included. Procedural success was 59% to 100% and catheter-directed thrombolysis was used as an adjunct in 16% to 53%. No deaths or major bleeding complications were reported. Pharmacomechanical thrombolysis leads to the immediate resolution of clinical symptoms of DVT in the majority of patients. Pharmacomechanical thrombolysis may be a safe and novel method, when appropriate expertise and resources are available, for the treatment of symptomatic acute and chronic DVT.