•Low CD3+ TILs rate was associated with shorter OS in those with stage II colon cancer who did not receive adjuvant therapy.•CD3+ TILs rate was not prognostic for patients with stage II colon cancer ...who had adjuvant therapy.•Low CD3+ TILs rate may be an additional risk factor for stage II colon cancer patients who did not have adjuvant therapy yet.
High tumor infiltrating lymphocytes (TILs) density was previously shown to be associated with favorable prognosis for patients with colon cancer (CC). However, the impact of TILs on overall survival (OS) of stage II CC patients who received adjuvant chemotherapy (ADJ) or not (no-ADJ) is unknown. We assessed the prognostic value of CD3+ TILs in stage II CC patients according to whether they had ADJ or not.
Patients treated with curative surgery for stage II CC (2002–2013) were selected from the Santa Maria alle Scotte Hospital registry. TILs at the invasive front, center of tumor, and stroma were determined by immunohistochemistry and manually quantified as the rate of TILs/total tissue areas. High TILs (H-TILs) was defined as >20%. Patients were categorized as high or low TILs (L-TILs) and ADJ or no-ADJ.
Of the 678 patients included, 137 (20%) received ADJ and 541 (80%) did not. The distribution of the 4 groups were: 16% (L-TIL/ADJ), 64% (L-TIL/no-ADJ), 5% (H-TIL/ADJ), 15% (H-TIL/no-ADJ). Compared to H-TILs/no-ADJ, ADJ patients showed a significantly increased OS (P<.01) regardless of the TILs rate whereas L-TILs/no-ADJ had significantly decreased OS and higher risk of death (HR=1.41; 95% CI, 1.06–1.88; P<.0001). On multivariable analysis, the unfavorable prognostic value of L-TILs (vs. H-TILs) for no-ADJ patients was confirmed (HR=1.36; 95% CI 1.02, 1.82; P=.0373).
Low CD3+ TILs rate was associated with shorter OS in those with stage II colon cancer who did not receive adjuvant therapy. Low CD3+ TILs could be considered an additional risk factor for still ADJ-untreated stage II CC patients, which could facilitate clinical decision making.
Natural substances present in herbal preparations should be carefully used because they can give toxic or therapeutic effects despite of their amount or the way of administration. The safety of ...products of vegetable origin must be assessed before commercialisation by monitoring the active ingredients and their metabolites. This study was therefore designed to identify and quantify arbutin and its metabolite hydroquinone, naturally present in Arctostaphylos uva-ursi (L.) Spreng plant in rat plasma, after an acute and subacute administration of aqueous arbutin solution in Wistar rats. For this purpose a reversed-phase high-performance liquid chromatography coupled with photodiode array detection was developed to assess the pharmacokinetic of arbutin and hydroquinone in plasma of female rats treated with aqueous arbutin solutions. The detection (arbutin: 0.0617 µg/ml and hydroquinone 0.0120 µg/ml) and quantification (arbutin: 0.2060 µg/ml and hydroquinone: 0.0400 µg/ml) limits were determined. At the arbutin concentration level of 10.7 µg/ml repeatability was 13.33% and its recovery 93.4±6.93%, while at the hydroquinone concentration level of 10.6 µg/ml repeatability was 11.66% and its recovery 92.9±7.75%. Furthermore the method was fully validated and the obtained data indicate that the new method provides good performances.
The aim of this report is to investigate the activity of ramucirumab in combination with paclitaxel in patients with metastatic gastric cancer (GC) and lung metastases. We retrospectively reviewed ...clinical data from patients with GC treated in second line with ramucirumab and paclitaxel according to the presence or not of lung metastases. Thirty-one patients were eligible. Five (16.1%) patients had lung metastases. The median progression-free survival was 156 days in patients without lung metastases compared with 54 days in patients with lung metastases. The median survival also showed a trend in favour of patients without lung metastases. Despite the small number of patients and the retrospective nature of the data, our analysis showed relatively poor efficacy of ramucirumab plus paclitaxel as a second-line treatment in patients with lung metastases from GC. Further studies are required to evaluate novel treatments in this subset of patients.
Aims/hypothesis. Induction of tolerance to insulin is achievable in animal models of Type I (insulin-dependent) Diabetes mellitus by oral treatment with this hormone, which can lead to prevention of ...the disease. In the Diabetes Prevention Trial of Type I diabetes (DPT-1), oral insulin is given with the aim of preventing disease insurgence. We investigated whether if given at diagnosis of Type I diabetes in humans, oral insulin can still act as a tolerogen and therefore preserve residual beta-cell function, which is known to be substantial at diagnosis. Methods. A double-blind trial was carried out in patients (mean age ± SD: 14 ± 8 years) with recent-onset Type I diabetes to whom oral insulin (5 mg daily) or placebo was given for 12 months in addition to intensive subcutaneous insulin therapy. A total of 82 patients with clinical Type I diabetes ( < 4 weeks duration) were studied. Basal C peptide and glycated haemoglobin were measured and the insulin requirement monitored every 3 months up to 1 year. Insulin antibodies were also measured in 27 patients treated with oral insulin and in 18 patients receiving placebo at the beginning of the trial and after 3, 6 and 12 months of treatment. Results. The trial was completed by 80 patients. Overall and without distinction between age at diagnosis, at 3, 6, 9 and 12 months baseline mean C-peptide secretion in patients treated with oral insulin did not differ from that of those patients treated with placebo. In patients younger than 15 years a tendency for lower C-peptide values at 9 and 12 months was observed in the oral insulin group. Insulin requirement at 1 year was similar between the two groups as well as the percentage of glycated haemoglobin. Finally, IgG insulin antibodies were similar in the two groups at each time point. Conclusion/interpretation. The results of this study indicate that the addition of 5 mg of oral insulin does not modify the course of the disease in the first year after diagnosis and probably does not statistically affect the humoral immune response against insulin. Diabetologia (2000) 43: 1000-1004
Few data are available on lung dysfunction in children with diabetes. We studied the association of pulmonary function variables (flows, volumes and alveolar capillary diffusion) with disease-related ...variables in children with type 1 diabetes mellitus.
We studied 39 children with type 1 diabetes (mean age 10.9+/-2.6 years, disease duration 3.6+/-2.4 years, insulin.kg(-1).day(-1) 0.77+/-0.31) and 30 healthy control children (mean age 10.4+/-3.0 years). Pulmonary function tests included spirometry, N(2) wash-out and the single-breath diffusing capacity for carbon monoxide (DL(CO)) corrected for the alveolar volume (DL(CO)/V(A)). Glycaemic control was assessed on the basis of HbA(1)c, with HbA(1)c values of 8% or less considered to indicate good glycaemic control, and HbA(1)c values of 8% or more considered to indicate poor control.
Children with poor glycaemic control had comparable percentage values for predicted flows and volumes but lower DL(CO)/V(A) values than children with good glycaemic control and healthy control children (86.7+/-12.6 vs 99.8+/-18.4 and 102.0+/-15.7; p<0.05). The predicted DL(CO)/V(A) percentages correlated with HbA(1)c levels (r=-0.39, p=0.013). A multiple regression analysis (stepwise model) controlling for HbA(1)c levels and other disease-related variables (age of disease onset, disease duration, daily insulin dose/kg, sex) identified HbA(1)c levels as the sole predictor of DL(CO)/V(A) in percent.
In children with type 1 diabetes, the diffusing capacity diminishes early in childhood and is associated with poor metabolic control. Although low DL(CO)/V(A) levels in these children probably reflect pulmonary microangiopathy induced by type 1 diabetes, other factors presumably influencing CO diffusion capacity measurements (e.g. a left shift in HbA(1)c resulting in high O(2) binding and low CO binding) could explain the apparent capillary and alveolar basal membrane dysfunction.
Patients with diabetes mellitus commonly have cardiovascular autonomic dysfunction and an abnormal ventilatory pattern during sleep. Few data are available on these changes in childhood diabetes. We ...investigated whether young diabetic children with or without diabetic neuropathy have ventilatory dysfunction during sleep and if so, whether these autonomic changes are related to the duration of diabetes and glycaemic control.
We studied 25 children with insulin-dependent diabetes mellitus (19 boys, mean age 7.72 +/- 1.99 years). All patients were insulin-dependent at diagnosis; blood samples for HbA1c assay were collected on the morning before testing and at 3-month intervals during the preceding year. Patients and control subjects (20 age-matched healthy children, 15 boys) underwent overnight polysomnography.
More diabetic patients than control subjects had sleep apnoeas (p = 0.006); apnoeas in patients also lasted longer (p = 0.07). Patients with poorly controlled diabetes had more apnoeas than patients with well-controlled diabetes and than healthy control subjects (p < 0.0001). Respiratory events during sleep correlated significantly with glycaemic control (r = 0.360; p = 0.09) and with the duration of diabetes (r = 0.430; p = 0.04).
We conclude that respiratory control is compromised very early in children with diabetes. These anomalies are closely related to the duration of diabetes and to glycaemic control. In young children with diabetes, screening of ventilatory control using recording techniques that are simpler than polysomnography could provide an early indication that an adverse cardiopulmonary reaction has begun.
Nicotinamide has been recently introduced, in addition to intensive insulin therapy for patients with recent-onset insulin-dependent diabetes mellitus (IDDM) to protect beta cells from end-stage ...destruction. However, available data are conflicting. A double blind trial in 56 newly-diagnosed IDDM patients receiving nicotinamide for 12 months at a dose of 25 mg/kg body weight or placebo was designed in order to determine whether this treatment could improve the integrated parameters of metabolic control (insulin dose, glycated haemoglobin and C-peptide secretion) in the year after diagnosis. In addition to nicotinamide or placebo, patients received three to four insulin injections daily to optimize blood glucose levels. Patients treated with nicotinamide or placebo received similar doses of insulin during follow-up and 1 year after diagnosis with comparable glycated haemoglobin levels 6.7 +/- 1.8% nicotinamide vs 7.1 +/- 0.6% placebo). Basal and glucagon stimulated C-peptide secretion detectable at diagnosis were similarly preserved in the course of 12 months follow-up both in nicotinamide and placebo treated patients. No adverse effects were observed in patients receiving nicotinamide. When age at diagnosis was taken into account, nicotinamide treated older patients ( > 15 years of age) showed significantly higher stimulated C-peptide secretion than placebo treated patients (p < 0.02). These results suggest that nicotinamide can preserve and improve stimulated beta-cell function only in patients diagnosed after puberty.
The relative importance of genetic and environmental factors in causing insulin-dependent diabetes mellitus (IDDM) is unknown. We studied this question by assessing the incidence of the disease in ...children, born in a region with a low incidence of IDDM (Lazio), but whose parents came from a region with high incidence (Sardinia).
We identified all IDDM cases that occurred between 1989 and 1994. We used as the denominator the number of children aged 0-14 born in Lazio of Sardinian parents to calculate incidence. We compared this rate with the incidences of IDDM in the populations of Lazio and Sardinia.
The age-adjusted incidence of IDDM in Sardinian-heritage children born and living in Lazio was 33.8 per 100,000 per year (95% CI 7.0-99.0) for those with two Sardinian parents, and 15.9 (8.7-26.6) for those with only one parent from Sardinia. The former incidence was not different from that recorded in Sardinia (34.4, 31.3-37.9), but was fourtold that of Lazio-heritage children (7.9, 7.1-8.8).
Our results show that two different ethnic groups living in the same region have a fourfold difference in incidence of IDDM. Children of Sardinian-heritage born in Lazio have the same incidence as the population of origin, which is genetically prone to the disease. Moreover, children with one Sardinian parent had a rate half that of Sardinians and double that of the indigenous population. We conclude that in a given population genetic susceptibility determines the frequency of IDDM in response to the environmental challenge.
Congenital autoimmune diabetes mellitus Cilio, C M; Bosco, S; Moretti, C ...
New England journal of medicine/The New England journal of medicine,
2000-May-18, Letnik:
342, Številka:
20
Journal Article
PDF
