Effect of primary tumor resection on overall survival in patients with stage IV breast cancer

We aimed to evaluate the effect of primary tumor resection on overall survival in stage IV breast cancer patients. In total, 284 breast cancer patients presenting with breast cancer at stage IV at initial diagnosis, between 2001 and 2014, were enrolled in the study. Patients were divided into two groups based on surgical resection of the primary tumor. Overall survival (OS) between the two groups was analyzed. Patients in the surgery group (n = 92) had smaller tumors than those in the no‐surgery group (n = 192, T0‐1:17.7% vs 34.8%, P < 0.001). The surgery group more often had negative nodal status (5.7% vs 33.7%, P < 0.001). Multiple metastatic organ sites were more common in the no‐surgery group than in the surgery group (55.7% vs 15.2%, P < 0.001). The surgery group showed a better OS than the no‐surgery group (P = 0.01). Multivariate analysis showed that surgical resection of primary tumors tended to be associated with improved OS (HR = 0.67, P = 0.055). T stage, ER, HER2 and metastatic organ sites were independent prognostic factors for OS in multivariate analysis. Surgical resection of the primary tumor may be a treatment option for patients with stage IV disease and may not have a negative effect on overall survival.     

Characteristics of and risk factors for colorectal neoplasms in young adults in a screening population

AIM: To investigate prevalence and risk factors for colorectal neoplasms in adults aged 50 years, for whom screening is not recommended.METHODS: This cross-sectional study compared prevalence and characteristics of colorectal and advanced adenomas in patients aged 50 years who underwent colonoscopy screening with subjects aged ≥ 50 years. To evaluate risk factors for colorectal and advanced adenoma in young adults, we used multivariable logistic regression models. Colorectal neoplasm characteristics were evaluated and compared with those in older patients.RESULTS: Among 2819 patients included, prevalences of colorectal adenoma and advanced adenoma were 19.7% and 1.5%, respectively. As patient age increased, so did the prevalence of colorectal neoplasm. However, prevalence of advanced adenoma did not differ between age-groups 45-49 years and ≥ 50 years(OR = 0.43, 95%CI: 0.17-1.07, P = 0.070). In younger age-group( 50 years), colorectal adenoma was significantly associated with older age, waist circumference(OR = 1.72, 95%CI: 1.15-2.55, P = 0.008), and current smoking(OR = 1.60, 95%CI: 1.07-2.41, P = 0.023). Alcohol consumption was an independent risk factor for colorectal advanced adenoma(OR = 3.69, 95%CI: 1.08-12.54, P = 0.037). Multiple neoplasms and large neoplasms(≥ 1 cm) were more prevalent in subjects ≥ 50 years.CONCLUSION: Current screening strategies for colorectal cancer may need to be amended to account for patient age, especially in young subjects with abdominal obesity, current smoking and alcohol consumption.     

Hypersensitivity pneumonitis associated with azathioprine therapy in a patient with granulomatosis with polyangiitis

Granulomatosis with polyangiitis (GPA), an autoimmune disease characterized by inflammatory granulomas and necrotizing small-vessel vasculitis, primarily affects the respiratory tract and kidneys. Azathioprine (AZA) is a purine analog that is commonly used for maintaining GPA remission after induction therapy with cyclophosphamide. While the dose-dependent side effects of AZA are common and well known, hypersensitivity reactions such as pulmonary toxicity are rare. Here, we describe a case involving a 38-year-old man with GPA-associated pauci-immune crescentic glomerulonephritis who developed subacute hypersensitivity pneumonitis (HP) during AZA maintenance therapy. Five months after the initiation of AZA administration (100 mg/day), the patient was admitted with a 7-day history of cough, dyspnea, and fever. High-resolution computed tomography of the chest showed ill-defined centrilobular nodules and diffuse ground-glass opacities in both lung fields. Bronchoscopy with bronchoalveolar lavage was negative for infectious etiologies. A transbronchial lung biopsy specimen revealed poorly formed non-necrotizing granulomas. A chest radiograph obtained at 2 weeks after discontinuation of AZA showed normal findings. The findings from this case suggest that AZA-induced HP should be considered as a differential diagnosis when a patient with GPA exhibits fresh pulmonary lesions accompanied by respiratory symptoms during AZA therapy.     

Low IGFBP-1 is a marker of impaired skin vascular response to both endothelial and non-endothelial stimulation in healthy males

Vascular endothelial dysfunction is an early event in the development of atherosclerosis and is also linked to insulin resistance and type 2 diabetes mellitus. Serum IGFBP-1 and IGF can be used as markers of insulin sensitivity and secretion. The aim was to investigate if microvascular reactivity in healthy males with and without heredity of type 2 diabetes mellitus is related to serum levels of IGF-1 and its binding protein IGFBP-1.Thirty-six middle-aged male subjects free of medication, non-smokers and with normal oral glucose tolerance test were investigated. Nineteen of the subjects had known heredity for type 2 diabetes. The groups were matched for age and body mass index. Skin microcirculation was studied with laser Doppler perfusion imaging before and after iontophoretic application of endothelial (acetylcholine (Ach)) and non-endothelial dependent (sodium nitroprusside (SNP)) substances. The microvascular responses to iontophoretic application of Ach and SNP, respectively, were weaker (p = 0.01 and p = 0.02, respectively) in subjects with diabetes heredity than in those without. In subjects without heredity a significant correlation was observed between the peak microvascular responses to Ach (r = 0.57; p < 0.02), SNP (r = 0.51; p < 0.05), and levels of IGFBP-1, while no significant correlation was found in subjects with diabetes heredity. In summary our study shows that healthy male subjects with no heredity for type 2 diabetes have low fasting IGFBP-1 which were associated with impaired microvascular responses to both endothelial and non-endothelial stimulation.     

Apoptosis-like death-inducing property of tachyplesin I in Escherichia coli

 Antimicrobial peptide (AMP) derived from the horseshoe crab, tachyplesin I (KWCFRVCYRGICYRRCR–NH₂), displayed the apparent antimicrobial activity with low cytotoxicity, suggesting its efficacy as an attractive agent but still lacks the understandings regarding its mechanism(s). Hence, the study focused on investigating the antibacterial mode of action of tachyplesin I against Escherichia coli. Based on the reactive oxygen species generation displayed in several antimicrobial effects, the detection of superoxide anion and nitric oxide were verified after tachyplesin I treatment. Substantial increment of two molecules was followed by the imbalance in intracellular ion concentration, noticeably magnesium and calcium. The series of stages led to hydroxyl radical generation with reduced glutathione, followed by damage in DNA due to oxidative stress. Eventually, the apoptosis-like death in E. coli was monitored in DNA fragmentation-dependent manner due to the tachyplesin I treatment, verified by membrane depolarization, caspase-like protein activation, and phosphatidylserine exposure. Accordingly, tachyplesin I induces apoptosis-like death in E. coli, suggesting the potential of being a candidate for regulating bacterial infection.     

Exploring multidimensional operationalizations of precarious employment in Swedish register data – a typological approach and a summative score approach

Objectives:This study aimed to explore multidimensional operationalizations of precarious employment (PE) in Swedish register data using two approaches: (i) a typological approach and (ii) a dimensional, summative scale approach. It also examined the distribution of sociodemographic and occupational characteristics of precarious employees in Sweden.Method:Register data was retrieved on individuals and their employers in the Swedish workforce. Five items corresponding to three dimensions of PE were operationalized: contractual relationship insecurity, contractual temporariness, multiple jobs/sectors, income level, and lack of unionization. First, latent class analysis was applied and a typology of six employment types emerged. Second, a summative scale was constructed by scoring all PE-items.Results:Three types of PE were found using the typological approach, which were characterized by direct employment, solo self-employment and multiple job holding, respectively. The summative scale score ranged between -10 and +2 (average: -1.8). Particularly poor scores were seen for solo self-employed, multiple job holders/multiple sectors, and low income. Female gender, young age, low education and foreign origin were prone to precariousness. PE was more frequent among certain economic sectors and occupations.Conclusions:Using an existing register of labor market data, two operationalizations of PE were constructed and rendered promising for exposure assessment. Hence, the operationalizations could be of interest for countries with similar data structure. Both approaches highlighted precarious combinations of employment conditions and pointed towards the existence of a wide continuum of precariousness on the labor market. Etiological studies and research assessing trends over time are needed to validate these findings.