Molecular profiling of the colon cancer in South-Eastern Romania: Results from the MERCUR study

Colorectal cancer is a heterogeneous disease with multiple epigenetic alterations and different molecular features. The molecular classification is based on 2 major distinct pathways: microsatellite stable pathway and the microsatellite instability pathway. Molecular profiling of colorectal cancer provides important information regarding treatment and prognosis. Aim of the study was to assess the frequency of microsatellite instability in colon cancer and the clinicopathological characteristics of the tumors with high level of microsatellite instability (MSI-H) in our region. The secondary outcome was to assess the frequency of v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutations in colon cancer.The study included 129 patients with colon cancer fit for surgery. Demographic data, clinical and pathological data, immunohistochemistry staining pattern (4 mismatch repair proteins were investigated), and BRAF gene mutations were assessed. According to microsatellite instability status by polymerase chain reaction, patients were divided into 3 groups: microsatellite stable (MSS) = 108 patients, high level of microsatellite instability (MSI-H) = 15 patients and low level of microsatellite instability (MSI-L) = 6 patients. Different clinicopathological comparisons between MSS and MSI-H patients, and between MSS and MSI-L patients were performed.Microsatellite instability was found in 16.3% patients: 11.6% had MSI-H and 4.7% had MSI-L. Significantly more patients in the MSI-H group than in the MSS group were female (P = .01) and had a family history of colon cancer (P < .001). MSI-H and MSI-L groups were associated with the ascending colon location of the tumors, were mostly type G3, T2, and stage I whereas MSS tumors were mostly G2, pT3, and stage III. Overall, BRAF mutations were identified in 18/129 patients (13.9%). BRAF mutant tumors were predominantly associated with MSI-H and MSI-L tumors. Immunohistochemistry had a sensitivity of 76% and a specificity of 89% in detecting MSI tumors and an accuracy of 87.6%.The frequency of microsatellite instability in our study was 16.3%. MSI-H is a distinct molecular phenotype of colon cancer with particular features: female gender, family history of colorectal cancer, a predilection for the ascending colon, poorly differentiated, predominantly T2, and stage I. The frequency of BRAF mutations was 13.9% and mutations were more often present in the MSI tumors.     

Adverse Childhood Events and Current Depressive Symptoms Among Women in Hawaii: 2010 BRFSS,Hawaii

Research on the association between adverse childhood events (ACEs) and depression among women in Hawaii is scarce. ACEs have been linked to unfavorable health behaviors such as smoking and binge drinking which are more prevalent in the state compared to the US overall. The concomitant presence of ACEs with smoking or binge drinking may explain the excess depression prevalence in Hawaii compared to the national average. Using data of women residing in the state (2010 Hawaii Behavioral Risk Factor Surveillance System Survey), we examined the association between ACEs count or type (household dysfunction and physical, verbal and sexual abuse) and current depressive symptoms (CDS), in addition to modification by current smoking status (smoked >100 cigarettes in a lifetime and currently smoke) and binge drinking (consumed ≥4 alcoholic beverage within the past month and in ≥1 occasion(s)). Evaluation of ACEs before age 18 consisted of 11 indicators. Eight indicators of the Patient Health Questionnaire (PHQ-8) were used to assess CDS. All analyses utilized logistic regression taking into account sampling design. The odds ratio of having CDS between those with versus without ACEs increased per increasing number of ACEs (1 ACE: OR = 2.11, CI = 1.16–3.81; 2 ACEs: OR = 2.90, CI = 1.51–5.58; 3 or 4 ACEs: OR = 3.94, CI = 2.13–7.32; 5+ ACEs: OR = 4.04, CI = 2.26–7.22). Household dysfunction (OR = 2.10, CI = 1.37–3.23), physical abuse (OR = 1.67, CI = 1.08–2.59), verbal abuse (OR = 3.21, CI = 2.03–5.09) and sexual abuse (OR = 1.68, CI = 1.04–2.71) were all positively associated with CDS. Verbal abuse had the strongest magnitude of association. Neither current smoking status nor binge drinking modified the relationship between ACEs count (or type) and CDS. In conclusion, the presence of ACEs among women in Hawaii was indicative of CDS in adulthood, notably verbal abuse. Further, a dose response existed between the number of ACEs and the odds for CDS. The concomitant exposure to ACEs and current smoking status or binge drinking did not elevate odds for CDS.     

Broad influenza-specific CD8+ T-cell responses in humanized mice vaccinated with influenza virus vaccines

The development of novel human vaccines would be greatly facilitated by the development of in vivo models that permit preclinical analysis of human immune responses. Here, we show that nonobese diabetic severe combined immunodeficiency (NOD/SCID) beta(2) microglobulin(-/-) mice, engrafted with human CD34+ hematopoietic progenitors and further reconstituted with T cells, can mount specific immune responses against influenza virus vaccines. Live attenuated trivalent influenza virus vaccine induces expansion of CD8+ T cells specific to influenza matrix protein (FluM1) and nonstructural protein 1 in blood, spleen, and lungs. On ex vivo exposure to influenza antigens, antigen-specific CD8+ T cells produce IFN-gamma and express cell-surface CD107a. FluM1-specific CD8+ T cells can be also expanded in mice vaccinated with inactivated trivalent influenza virus vaccine. Expansion of antigen-specific CD8+ T cells is dependent on reconstitution of the human myeloid compartment. Thus, this humanized mouse model permits preclinical testing of vaccines designed to induce cellular immunity, including those against influenza virus. Furthermore, this work sets the stage for systematic analysis of the in vivo functions of human DCs. This, in turn, will allow a new approach to the rational design and preclinical testing of vaccines that cannot be tested in human volunteers.     

Intracorneal hematoma after canaloplasty and clear cornea phacoemulsification: surgical management

Purpose. This is a case report of intracorneal hematoma after canaloplasty and clear cornea phacoemulsification. Methods. A 75-year-old woman presented with primary open angle glaucoma and visually significant cataract. Canaloplasty and clear corneal phacoemulsification were performed. Postoperatively she had an intracorneal hematoma, which was removed through a clear corneal tunnel. Results. Preoperative best-corrected visual acuity (BCVA) was 20/40 in the right eye and mean intraocular pressure (IOP) was 20 mmHg. Uneventful canaloplasty, clear corneal phacoemulsification, and implantation of a posterior chamber intraocular lens were performed. One day after the operation, BCVA was 20/400 in the right eye. The IOP was 8 mmHg. Anterior segment examination revealed a nasally located intrastromal hematoma between corneal stroma and Descemet membrane. The intracorneal hematoma was removed through a clear corneal tunnel. Six months postoperatively, BCVA was 20/25 in the right eye. The IOP with one medication was 17 mmHg. Conclusions. This operation was a minimally invasive technique to remove intrastromal hematocornea after viscocanaloplasty.     

Diffuse alveolar hemorrhage secondary to sarcoidosis

Clinical Rheumatology - Diffuse alveolar hemorrhage (DAH) is a pulmonary condition that can be caused by autoimmune disorders such as lupus, small vessel vasculitis, and antiphospholipid syndrome....