Computer-driven quantitative image analysis in the assessment of tumor cell and T cell features in diffuse large B cell lymphomas

Diffuse large B cell lymphoma (DLBCL) is recognized as the most common non-Hodgkin lymphoma subtype. Advanced high-resolution digital scans of pathology slides have enabled the development of computer-based image analysis algorithms that may assist pathologists in quantifying immunohistochemical stains. In this retrospective study, we reviewed data from 29 patients affected by DLBCL. In order to evaluate the number of tumor cells and microenvironment T cells, we performed an analysis of CD20, Ki67, and CD3 counts, assessed with the Positive Pixel Count algorithm embedded in the Aperio ImageScope software. A lower tumor cell count was observed in patients with a non-germinal center immunophenotype, high LDH, splenomegaly and an IPI?≥?3. A lower number of CD3 was observed in patients with bulky disease, an IPI?≥?3 and disease stage 3–4. Overall, these data confirm that quantitative analysis of the tumor cells and of the tumor microenvironment by means of computer-driven quantitative image analysis may add new information in DLBCL diagnosis.     

Preliminary Report of Major Surgery in Liver Transplant Recipients Receiving m-TOR Inhibitors without Therapeutic Discontinuation

Introduction

Mammalian target rapamycin inhibitors (m-TORi) are increasingly used in patients undergoing liver transplantation (LT). Yet, there is rising concern that they also could impair wound healing and favor the development of several surgical complications. This report was designed to evaluate both feasibility and safety of major surgery in liver transplant recipients receiving m-TORi–based immunosuppression without therapeutic discontinuation.

Methods

From 2007 to 2012, six liver transplant recipients underwent nine major abdominal or thoracic surgical procedures without m-TORi discontinuation or specific dosage adjustment. Their characteristics and postoperative outcomes were retrospectively analyzed.

Results

Indications for m-TORi were de novo or recurrent malignant disease in five patients and calcineurin inhibitors related neurologic toxicity in one patient. Abdominal procedures, thoracic procedures, and combined thoracic and abdominal procedures were performed in six, two, and one cases respectively. Emergency surgery was performed in one case and elective procedures were performed in eight cases, including five for malignant disease and three for late surgical complications following LT. No patient died postoperatively. One major complication was observed, but no patient required reoperation. No evisceration, incisional surgical site infection, or lymphocele occurred.

Conclusions

Major surgery in liver transplant recipients receiving m-TOR inhibitors appears both feasible and safe without therapeutic discontinuation or specific dosage adjustment.     

Immunoparalysis in critically ill children

Immunoparalysis is associated with poorer outcomes in the paediatric intensive care unit (PICU) setting. We aimed to determine the group of patients with higher chances of immunoparalysis and correlate this status with increased risks of nosocomial infection and adverse clinical parameters. We conducted an exploratory study with prospective data collection in a university-affiliated tertiary medical, surgical, and cardiac PICU. Fifteen patients with multiple organ dysfunction syndrome were included over a period of 6 months. Monocyte's human leucocyte antigen (HLA)-DR expression and tumour necrosis factor (TNF)-α and interleukin (IL)-6 production were measured by flow-cytometry at three time points (T1 = 1–2 days; T2 = 3–5 days; T3 = 6–8 days). Using the paediatric logistic organ dysfunction-2 score to assess initial disease severity, we established the optimal cut-off values of the evaluated parameters to identify the subset of patients with a higher probability of immunoparalysis. A comparative analysis was performed between them. Sixty per cent were males; the median age was 4.1 years. Considering the presence of two criteria in T1 (classical monocytes mean fluorescence intensity [MFI] for HLA-DR ≤ 1758.5, area under the curve (AUC) = 0.775; and frequency of monocytes producing IL-6 ≤ 68.5%, AUC = 0.905) or in T3 (classical monocytes MFI of HLA-DR ≤ 2587.5, AUC = 0.675; and frequency of monocytes producing TNF-α ≤ 93.5%, AUC = 0.833), a variable to define immunoparalysis was obtained (100% sensitivity, 81.5% specificity). Forty per cent of patients were assigned to the immunoparalysis group. In this: a higher frequency of nosocomial infection (p = 0.011), vasoactive inotropic score (p = 0.014) and length of hospital stay (p = 0.036) was observed. In the subgroup with the diagnosis of sepsis/septic shock (n = 5), patients showed higher percentages of non-classical monocytes (p = 0.004). No mortality was recorded. A reduction in classical monocytes HLA-DR expression with lower frequencies of monocytes producing TNF-α and IL-6 during the first week of critical illness, appears to be a good marker of immunoparalysis; these findings relate to an increased risk of nosocomial infection and deleterious outcomes. The increased frequency of non-classical monocytes in patients with sepsis/septic shock is suggestive of a better prognosis.     

Attitude and practice of substance misuse and dietary supplements to improve performance in sport

ABSTRACT

The knowledge of using performance-enhancing drugs and supplements is caused by psychological and social dynamics. Moreover, athletes used pharmaceuticals to improve their performance, which is commonly known as doping. Doping in sports is the “use of prohibited techniques and/or the assumption of prohibited substances by athletes in order to increase physical performances”. If an individual believes that capacity is not related to commitment, then they are more exposed to the use of performance-enhancing drugs. This misuse is ethically and legally incorrect. We will agree that sport is essentially under the current anti-doping campaign executed by a coordinated alliance between the World Anti-Doping Agency (WADA), law enforcement authorities and sports organizers. Doping is a public health issue and not simply a problem inside the professional sports community. Opinions are spreading in support of liberalization of doping. Some are based on the circumstances that currently the values of equality and health are not protected and, therefore, the liberalization of doping doesn’t result in a change in the current situation. Indeed, the prohibitionist attitude involves the search for substances and methods of administration increasingly dangerous. This review is a portrait of this issue and explores some arguments concerning various aspects of the problem.