The Emerging Role of Neutrophil to Lymphocyte Ratio in Determining Colorectal Cancer Treatment Outcomes: A Systematic Review and Meta-Analysis

Background

There is growing evidence suggesting that the neutrophil to lymphocyte ratio (NLR) can act as an independent predictor of long-term outcomes in patients undergoing treatment for colorectal cancer (CRC). This study aims to systematically review the role of NLR in predicting survival for patients with CRC undergoing treatments, and to evaluate its utility within a CRC surveillance program.

Methods

This meta-analysis was performed according to PRISMA guidelines. Outcomes of interest included disease-free survival (DFS) for patients undergoing treatment with curative intent and progression-free survival (PFS) in patients undergoing treatments with palliative intent.

Results

Thirteen observational cohort studies published from 2007 to 2013 evaluated the role of NLR as a predictor of outcome following treatment for CRC. These included (i) patients undergoing surgery to resect the primary cancer (seven studies); (ii) those undergoing palliative chemotherapy (three studies); and (iii) patients undergoing potentially curative treatments for CRC liver metastases (three studies). When all studies were considered, a high pretreatment NLR independently predicted survival (HR 2.08; 95 % CI 1.64–2.64). A high NLR also predicted significantly poorer survival in each of the three groups. Finally, over a 3-year follow-up period, high NLR became a significant predictor of poor outcome at year 2 (HR 2.76; 95 % CI 2.06–3.69; p < 0.00001) and 3 (HR 2.03; 95 % CI 1.48–2.78; p < 0.0001), but not in the first year of follow-up (HR 1.47; 95 % CI 0.89–2.41; p = 0.13).

Conclusions

Elevated preoperative NLR is associated with poorer survival in CRC patients undergoing treatment and may have a role in CRC surveillance programs as a means of delivering more personalized cancer care.     

Syngeneic transplantation with peripheral blood mononuclear cells collected after the administration of recombinant human granulocyte colony-stimulating factor

Five syngeneic transplants were performed in four patients following myeloablative therapy using unmodified peripheral blood mononuclear cells (PBMCs) collected after the administration of recombinant human granulocyte colony stimulating factor (rhG-CSF) to normal donors. The only toxicity experienced by the four normal donors was bone pain. Four patients received two collections of PBMCs, and a second transplant was performed in one patient with one collection. The patients received a median of 20.53 x 10(8) total nucleated cells/kg (range 20 to 25.5), 11.3 x 10(8) total mononuclear cells/kg (range 6.52 to 17.2), 113.1 x 10(4)/kg CFU-GM (range 46.7 to 211.8) and 9.6 x 10(6) CD34+ cells/kg (range 1.6 to 12.6) Post-transplant growth factors were not administered. The median time to an absolute neutrophil count greater than 0.5 x 10(9)/L was 14 days (range 10 to 18). The median time to platelet transfusion independence was 11 days (range 10 to 13). Two patients had the number of CD3+ T lymphocytes determined in the pheresis product. An average of 3.04 x 10(10) CD3+ cells were collected per pheresis. This represents an approximate 1 log increase over the number of T lymphocytes in a typical bone marrow transplant. Rh-GCSF can be used to mobilize peripheral blood progenitor cells from normal donors with minimal toxicity. Studies of allogeneic transplants using PBMCs collected after rhG-CSF administration to determine permanent grafting ability and the incidence and severity of graft-versus-host disease are warranted.     

Major role for neuronal death during brain development: refinement of topographical connections.

The precision of the topographic projection from the isthmo-optic nucleus (ION) to the retina has been examined in chicken embryos and chicks by the retrograde transport of a fluorescent carbocyanine dye from restricted retinal sites. At all ages, the labeled neurons are most numerous in the topographically appropriate part of the ION, but in younger embryos up to 49% of them are found outside this region. The distribution of these "aberrantly" projecting neurons is variable, but they generally occur throughout the entire ION. They all die during the ION's period of neuronal death, accounting for most of the 60% cell loss that then occurs. We therefore suggest that a major role of neuronal death during brain development is to reduce the imprecision of neuronal connections.     

Idiopathic CD4 Lymphocytopenia: Clinical and Immunologic Characteristics and Follow-Up of 40 Patients

Idiopathic CD4 T lymphocytopenia (ICL) is a rare and severe condition with limited available data. We conducted a French multicenter study to analyze the clinical and immunologic characteristics of a cohort of patients with ICL according to the Centers for Disease Control criteria.We recruited 40 patients (24 female) of mean age 44.2 ± 12.2 (19–70) years. Patients underwent T-lymphocyte phenotyping and lymphoproliferation assay at diagnosis, and experiments related to thymic function and interferon (IFN)-γ release by natural killer (NK) cell were performed. Mean follow-up was 6.9 ± 6.7 (0.14–24.3) years. Infectious, autoimmune, and neoplastic events were recorded, as were outcomes of interleukin 2 therapy.In all, 25 patients had opportunistic infections (12 with human papillomavirus infection), 14 had autoimmune symptoms, 5 had malignancies, and 8 had mild or no symptoms. At the time of diagnosis, the mean cell counts were as follows: mean CD4 cell count: 127/mm³ (range, 4–294); mean CD8: 236/mm³ (range, 1–1293); mean CD19: 113/mm³ (range, 3–547); and mean NK cell count: 122/mm³ (range, 5–416). Most patients had deficiency in CD8, CD19, and/or NK cells. Cytotoxic function of NK cells was normal, and patients with infections had a significantly lower NK cell count than those without (p = 0.01). Patients with autoimmune manifestations had increased CD8 T-cell count. Proliferation of thymic precursors, as assessed by T-cell rearrangement excision circles, was increased. Six patients died (15%). CD4 T-cell count <150/mm³ and NK cell count <100/mm³ were predictors of death.In conclusion, ICL is a heterogeneous disorder often associated with deficiencies in CD8, CD19, and/or NK cells. Long-term prognosis may be related to initial CD4 and NK cell deficiency.Abbreviations: AIHA = autoimmune hemolytic anemia, CDC = Centers for Disease Control, CMV = cytomegalovirus, cpm = count per minute, CVID = common variable immunodeficiency, CXCR4 = C-X-C chemokine receptor type 4, HIV = human immunodeficiency virus, HLA = human leukocyte antigen, HPV = human papillomavirus, HTLV-1/2 = human T-cell lymphotropic 1/2, ICL = idiopathic CD4 T lymphocytopenia, IFN-γ = interferon-γ, IL = interleukin, JC virus = John Cunningham virus, LPA = lymphocyte proliferation assay, NK = natural killer, P = patient, PBMC = peripheral blood mononuclear cell, Pwd = pokeweed, SI = stimulation index, sj = signal joint, TREC = T-cell rearrangement excision circle     

Epidemiology and diagnosis of pulmonary embolism in lung cancer patients: is there a role for age adjusted D-dimers cutoff?

Journal of Thrombosis and Thrombolysis - Our knowledge about the incidence of pulmonary embolism (PE) and the performance of age adjusted D-dimers (Dd) cutoff amongst patients with lung cancer (LC)...     

Brief and extended abstinence from chronic oral methylphenidate treatment produces reversible behavioral and physiological effects

Methylphenidate (MP) is a commonly prescribed psychostimulant to individuals with Attention Deficit Hyperactivity Disorder, and is often used illicitly among healthy individuals with intermittent breaks to coincide with breaks from school. This study examined how intermittent abstinence periods impact the physiological and behavioral effects of chronic oral MP self-administration in rats, and whether these effects persist following prolonged abstinence from the drug. Rats were treated orally with water, low-dose (LD), or high-dose (HD) MP, beginning at PND 28. This daily access continued for three consecutive weeks followed by a 1-week abstinence; after three repeats of this cycle, there was a 5-week abstinence period. Throughout the study, we examined body weight, food intake, locomotor activity, and anxiety- and depressive-like behaviors. During the treatment phase, HD MP decreased body weight, food intake, and depressive- and anxiety-like behaviors, while it increased locomotor activity. During intermittent abstinence, the effects of MP on locomotor activity were eliminated. During prolonged abstinence, most of the effects of HD MP were ameliorated to control levels, with the exception of weight loss and anxiolytic effects. These findings suggest that intermittent exposure to chronic MP causes physiological and behavioral effects that are mostly reversible following prolonged abstinence.