Real-world data of HER2-low metastatic breast cancer: A population based cohort study

BackgroundWith the introduction of investigational human epidermal growth factor receptor 2 (HER2) targeting treatments, thorough understanding of breast cancer with different HER2 expression levels is critical. The aim of this study was to compare clinicopathologic characteristics and survival of patients with metastatic breast cancer according to the level of HER2 expression.MethodsWomen with distant metastatic breast cancer during 2008–2016 were selected from PALGA, the Dutch Pathology Registry, and linked to the PHARMO Database Network. Breast cancer samples were categorised as HER2 immunohistochemistry score 0 (IHC0), HER2-low or HER2+.ResultsAmong women with hormone receptor (HR) positive metastatic breast cancer (n = 989), 373 (38%) cancers were HER2 IHC0, 472 (48%) were HER2-low and 144 (15%) were HER2+. Among HR negative patients (n = 272), the proportion of HER2 IHC0, HER2-low and HER2+ was 110 (40%), 104 (38%) and 58 (21%) respectively.Within the HR + cohort, patients with HER2 IHC0 or HER2-low cancer were significantly older compared to HER2+ patients. This age difference was not seen in the HR-cohort. The localisation of distant metastases differed significantly between HER2 IHC0 or HER2-low versus HER2+ cases. Survival rates did not differ markedly by subtypes.ConclusionSubstantial proportion of patients had a HER2-low breast cancer. No clear differences in survival were found when comparing HER2 and HR status. Getting more granular insights in the level of HER2 expression and addressing HER2-low as a separate category could help to assess the impact of emerging treatment strategies. Therefore, more detailed information on HER2 expression should be routinely reported.     

Effect of saccharin,a non-nutritive sweeteners,on insulin and blood glucose levels in healthy young men: A crossover trial

Background and aimsArtificial sweeteners used instead of sugar were considered as the best alternatives that have no endocrine effects. However, it has recently been suggested that artificial sweeteners may cause impaired metabolic parameters. The hypothesis of the study was there is an association between acute saccharin consumption and both glycemia and insulin response in young healthy adult men.Methods9 healthy adult males were included in this study. This study randomly provided participants with preloads as (a)300 ml of water, or 300 ml of water sweetened with (b)75 g of sucrose, (c)240 mg of saccharine (adjusted to the sweetness of 75 g of sucrose) 1 h before a standard breakfast.ResultsCompared to mean blood glucose and serum insulin after test drinks consumption, there was only one difference between sucrose and saccharin trials in the 15th minute (117.0 ± 18.70, 95.4 ± 5.64 mg/dl respectively, p < 0.05). At the 60th minute, insulin secretion (0.80 ± 0.27 pg/dl) after the sucrose trial was found significantly higher than the saccharin trial (0.53 ± 0.09 pg/dl) and water (0.49 ± 0.06 pg/dl) (p < 0.05). Although at all intervals (except 90th minute), the mean insulin is higher after the saccharin trial compared to the water trial, these were non-statistically significant differences (p > 0.05).ConclusionsConsequently, it was determined that saccharin had no glycemic effect. However, for the effect on serum insulin to be clarified, the long-term effects should be investigated.     

Peak C-reactive protein levels do not predict 30-day mortality for bacteremia: A retrospective cohort study

IntroductionAlthough peak C-reactive protein (CRP) levels are correlated with the prognosis of some diseases, there have been no reports regarding the association between peak CRP levels and mortality in patients with bacteremia. The present study aimed to determine the association between peak CRP levels and prognosis in patients with bacteremia.MethodsThis retrospective cohort study was conducted in a single tertiary hospital and included patients with bacteremia admitted to the emergency department from November 2012 to March 2017. Cox regression analysis was performed to examine the association between peak CRP levels and 30-day mortality. We also performed propensity score adjustment using potential confounding factors.ResultsOne hundred fifty-nine patients were included in the study. Peak CRP levels were significantly higher in the β-hemolytic streptococci (P = 0.001) and Streptococcus pneumoniae (P = 0.003) groups. The C-statistic of the multivariate logistic regression model for the propensity score was 0.88. For 30-day mortality, peak CRP levels >20 mg/dL did not show significance in the Cox regression analysis (hazard ratio, 0.866; 95% confidence interval, 0.489–1.537; P = 0.62). Even after propensity score adjustment, no significance was noted (hazard ratio, 0.865; 95% confidence interval, 0.399–1.876; P = 0.71).ConclusionsPeak CRP levels were not an independent predictor of mortality in patients with bacteremia in the emergency department. Clinicians should consider that patients with extremely high peak CRP levels do not necessarily have high mortality and vice versa.     

An Environmental Scan of the National and Provincial Diagnostic Reference Levels in Canada for Common Adult Computed Tomography Scans

Several regulatory bodies have agreed that low-dose radiation used in medical imaging is a weak carcinogen that follows a linear, non-threshold model of cancer risk. While avoiding radiation is the best course of action to mitigate risk, computed tomography (CT) scans are often critical for diagnosis. In addition to the as low as reasonably achievable principle, a more concrete method of dose reduction for common CT imaging exams is the use of a diagnostic reference level (DRL). This paper examines Canada's national DRL values from the recent CT survey and compares it to published provincial DRLs as well as the DRLs in the United Kingdom and the United States of America for the 3 most common CT exams: head, chest, and abdomen/pelvis. Canada compares well on the international scale, but it should consider using more electronic dose monitoring solutions to create a culture of dose optimization.     

Clinical Features and Survival of Single Hormone Receptor–Positive Breast Cancer: A Population-Based Study of 531,605 Patients

PurposeTo investigate the prognosis of single hormone receptor–positive (HR⁺) breast cancer (estrogen receptor [ER] positive and progesterone receptor [PR] negative, and ER⁻PR⁺) compared to double HR⁺ (ER⁺PR⁺) and double HR⁻ (ER⁻PR⁻) tumors.MethodsWe included 531,605 cases of invasive breast cancer between 1990 and 2012 from the US Surveillance, Epidemiology, and End Results (SEER) database for study and classified cases into 4 phenotypes according to expression of ER and PR: ER⁺PR⁺, ER⁺PR⁻, ER⁻PR⁺, and ER⁻PR⁻.ResultsOverall, 66,091 ER⁺PR⁻ tumors and 9320 ER⁻PR⁺ tumors were identified. The clinical characteristics of the ER⁺PR⁻ group were similar to those of the double HR⁺ group, while those of the ER⁻PR⁺ and double HR⁻ groups were similar. Overall survival of patients with single HR⁺ tumors was intermediate between that of double HR⁺ and double HR⁻ tumors. However, we observed no differences in disease-specific survival between ER⁻PR⁺ and ER⁻PR⁻ patients. In multivariate analysis, outcomes were similar. Relative to the double HR⁺ patient group, risk of death in the ER⁺PR⁻ group was higher (hazard ratio, 1.422, 95% confidence interval, 1.394-1.452). However, risk of death was comparable between ER⁻PR⁺ and ER⁻PR⁻ patients (hazard ratio, 1.03; 95% confidence interval, 0.98-1.08). Multivariate Cox proportional analysis showed that survival times of patients in the younger age bracket (< 60 years), those positive for human epidermal growth factor receptor 2 (HER2), and patients with tumor stage I-III were longer in the ER⁻PR⁺ group.ConclusionDisease-specific survival of single HR⁺ tumor cases was longer than that of double HR⁻ tumors but poorer than double HR⁺ tumors. However, differences in disease-specific survival were not significant between the ER⁻PR⁺ and ER⁻PR⁻ groups.     

A novel p.Gly417Valfs*12 mutation in the MTTP gene causing abetalipoproteinemia: Presentation of the first patient in Mexico and analysis of the previously reported cases

BackgroundOur aims were to describe the first Mexican patient with abetalipoproteinemia and to perform a comparative analysis of biochemical, clinical, and genetic characteristics of 100 cases reported in the literature.MethodsWe performed biochemical and molecular screenings in a Mexican girl with extremely low lipid levels and in her family. Further, we integrated and evaluated the characteristics of the cases with abetalipoproteinemia described in the literature.ResultsOur patient is a six‐year‐old girl who presented vomiting, chronic diarrhea, failure to thrive, malabsorption, acanthocytosis, anemia, transaminases elevation, and extremely low lipid levels. MTTP gene sequencing revealed homozygosity for a novel mutation p.Gly417Valfs*12 (G deletion c.1250). With the analysis of the reported cases, 60 clinical features (14 classical and 46 non‐classical) were observed, being the most common acanthocytosis (57.5%), malabsorption (43.7%), and diarrhea (42.5%); 48.8% of the patients presented only classic clinical features, while the remaining 51.2% developed secondary effects due to a fat‐soluble vitamin deficiency. An odds ratio analysis disclosed that patients diagnosed after 10 years of age have an increased risk for presenting clinical complications (OR = 18.0; 95% CI 6.0‐54.1, p < 0.0001). A great diversity of mutations in MTTP has been observed (n = 76, being the most common p.G865X and p.N139_E140) and some of them with possible residual activity.ConclusionThe first Mexican patient with abetalipoproteinemia presents a novel MTTP mutation p.Gly417Valfs*12. Three factors that could modulate the phenotype in abetalipoproteinemia were identified: age at diagnosis, treatment, and the causal mutation.