Comparative patterns of i-antigen expression, F-cell frequency and Hb A2 level in acute myeloid leukemia and in acute lymphoid leukemia

Hb F, Hb A₂ and i-antigen expression were investigated in adulthood acute leukemias. The study of i-antigen expression by immuno-agglutination and immunofluorescence showed that it is preferentially increased among AML patients. A similar result was obtained for F-cell frequency which was often increased in AML, while it was normal in ALL. Hb A₂ level was significantly lower in AML than in ALL. These differences between AML and ALL red cell patterns further suggest that the leukemic clone involves the erythroid lineage in AML but not in ALL.     

Estrogen receptor negative and progesterone receptor positive primary breast cancer: Pathological characteristics and clinical outcome

The expression of estrogen (ER) and progesterone (PgR) receptors was analyzed in a retrospective series of 3000 patients who had operable primary breast cancer. Patients were stratified according to ER and PgR status and the study was focused on the two groups (ER–PgR+ and ER–PgR–) of patients whose tumors contained low levels of ER (< 15 fmol/mg protein), regarding potential response to endocrine therapy. The comparison of clinical or histological characteristics between ER–PgR+ and ER–PgR– patients was analyzed as well as the disease-related death and survival. The mean follow-up was 86.3 months. Among the 529 ER–patients, 62 were PgR+ (12%), whereas 467 were PgR– (88%). The ER–PgR+ and ER–PgR– populations represented 2% and 15.6% of the overall population, respectively. In ER– tumors, the PgR status was significantly related to: age, menopausal status, tumor size, SBR grade, and histological type, but not to the type of surgical treatment or to lymph node involvement. ER–PgR+ tumors had smaller size (64% T1 vs 43%) (p=0.004) and were more frequently grade I (28% vs 12%) than ER–PgR– ones (p < 0.001). In addition, the patients with ER–PgR+ tumors were significantly younger (49.4 years vs 58.4 years; p < 0.0001), and were more frequently premenopausal (76% vs 36%; p < 0.001). The disease-free interval and the metastasis-free survival tended to be worse for ER–PgR– than for ER–PgR+ patients, but the difference was not statistically significant at 10 years. However, a small but significant difference in overall survival, in favor of the PgR+ group, was observed between the two groups during the first 5 years (p=0.03).We conclude that in combination with ER, PgR status defines a group of patients with clinical and biological specificity, which could be considered for specific endocrine therapy.     

A 38-gene expression signature to predict metastasis risk in node-positive breast cancer after systemic adjuvant chemotherapy: a genomic substudy of PACS01 clinical trial

Currently, no prognostic gene-expression signature (GES) established from node-positive breast cancer cohorts, able to predict evolution after systemic adjuvant chemotherapy, exists. Gene-expression profiles of 252 node-positive breast cancer patients (median follow-up: 7.7 years), mostly included in a randomized clinical trial (PACS01), receiving systemic adjuvant regimen, were determined by means of cDNA custom array. In the training cohort, we established a GES composed of 38 genes (38-GES) for the purpose of predicting metastasis-free survival. The 38-GES yielded unadjusted hazard ratio (HR) of 4.86 (95% confidence interval = 2.76–8.56). Even when adjusted with the best two clinicopathological prognostic indexes: Nottingham prognostic index (NPI) and Adjuvant!, 38-GES HRs were 3.30 (1.81–5.99) and 3.40 (1.85–6.24), respectively. Furthermore, 38-GES improved NPI and Adjuvant! classification. In particular, NPI intermediate-risk patients were divided into 2/3 close to low-risk group and 1/3 close to high-risk group (HR = 6.97 [2.51–19.36]). Similarly, Adjuvant! intermediate-risk patients were divided into 2/3 close to low-risk group and 1/3 close to high-risk group (HR = 4.34 [1.64–11.48]). The 38-GES was validated on gene-expression datasets from three external node-positive breast cancer subcohorts (n = 224) generated from different microarray platforms, with HR = 2.95 (1.74–5.01). Moreover, 38-GES showed prognostic performance in supplementary cohorts with different lymph-node status and endpoints (1,040 new patients). The 38-GES represents a robust tool able to type systemic adjuvant treated node-positive patients at high risk of metastatic relapse, and is especially powerful to refine NPI and Adjuvant! classification for those patients.     

Long‐chain polyunsaturated fatty acids in infant formula and cardiovascular markers in childhood

To investigate whether children who consumed infant formula supplemented with long‐chain polyunsaturated fatty acids (LCPUFAs) had a more favourable cardiovascular profile than children who consumed formula without these fatty acids, we used the Wheezing Illnesses Study Leidsche Rijn, a birth cohort that included 2,468 newborns between 2001 and 2014. Data on infant feeding were obtained by questionnaires. At age 5, blood pressure, carotid intima‐media thickness (CIMT), and carotid distension were measured. We used multivariable linear regression analysis to compare levels of cardiovascular markers in formula‐fed children born before and after the LCPUFA supplementation. To account for secular trends, we compared levels of cardiovascular markers in a control group of breastfed children from the same cohort born before and after the supplementation. Formula‐fed children born after the LCPUFA supplementation (n = 48) had no different systolic blood pressure (?2.58 mmHg, 95% confidence interval, CI [?5.5, 0.30]), diastolic blood pressure (?0.13 mmHg, 95% CI [?2.3, 2.1]), or carotid distension (24.8 MPa^?1, 95% CI [?47.1, 96.6]) and had a higher CIMT (18.6 μm, 95% CI [3.7, 33.5]) than formula‐fed children born before the supplementation (n = 163). In the control group, children born after the LCPUFA supplementation (n = 98) had no different systolic‐ or diastolic‐blood pressure, or CIMT, and a higher carotid distension than children born before the supplementation (n = 142). In conclusion, children who consumed infant formula supplemented with LCPUFAs did not have a more favourable cardiovascular profile in early childhood than children who consumed formula without LCPUFAs.     

Pitfalls in the genetic diagnosis of Hb S

Patients homozygous for Hb S need to be properly identified to start as early as possible a treatment that should avoid complications. For prevention and genetic counseling, carriers of Hb S have to be screened. Hb S is easily detected by several analytical systems, but other variants, usually harmless, may behave as Hb S, leading to false positive diagnosis. Some interactions may also cause difficulties in the qualitative or quantitative interpretation of a chromatography or electrophoresis profile. These problems may result from several causes among which the simultaneous presence of an α chain variant leading to the formation of tetramers having both an α and a β chain modified, the presence of a second mutation within the Hb S allele, the existence of a compound heterozygous state leading to some “Hb S trait with dominantly transmitted sickle cell disease (SCD)”, and the presence of thalassemic allele affecting the intracellular proportion of Hb S. In case of any “dominant Hb S trait” a thorough Hb study is always required. This work reports some of the difficulties observed by us, or reported in the literature, and propose how to avoid them and reach a correct diagnosis.     

Predicting health-related quality of life in dialysis patients: Factors related to negative outcome expectancies and social support

ObjectivesDialysis patients report a low health-related quality of life (HRQOL) due to high disease burden and far-reaching consequences of dialysis treatment. This study examined several cognitive-behavioral and social factors, with a focus on negative outcome expectancies, that might be relevant for HRQOL in end-stage kidney disease (ESKD) patients treated with dialysis.MethodsPatients treated with hemodialysis or peritoneal dialysis were recruited from Dutch hospitals and dialysis centers. Patients completed self-report questionnaires at baseline (n = 175) and six months follow-up (n = 130). Multiple regression analyses were performed.ResultsHigher scores on factors related to negative outcome expectancies at baseline, especially helplessness and worrying, and less perceived social support were significantly related to worse HRQOL six months later. When controlling for baseline HRQOL, besides sex and comorbidity, helplessness remained significantly predictive of worse HRQOL six months later, indicating that helplessness is associated with changes in HRQOL over time.ConclusionsNegative outcome expectancies and social support are relevant markers for HRQOL and/or changes in HRQOL over time.Practice implicationsNegative outcome expectancies could be prevented or diminished by enhanced treatment information, an improved patient-clinician relationship, and interventions that promote adaptive and realistic expectations. Additionally, increasing supportive social relationships could be a relevant treatment focus.