Contemporary treatment approaches for metastatic colorectal cancer driven by BRAF V600 mutations

The treatment of metastatic colorectal cancer (mCRC) harboring BRAF V600 mutations is challenging. These tumors are often refractory to standard treatment. Therefore, the patients may exhibit rapid clinical deterioration, depriving them of the chance to receive salvage therapy. In newly diagnosed patients with good performance status, the administration of an intensive chemotherapy regimen like FOLFOXIRI (5-fluorouracil, leucovorin, oxaliplatin, and irinotecan) along with the antiangiogenic agent bevacizumab can modify this aggressive behavior of the disease and improve patient clinical outcomes. The recently published results of the BEACON (Binimetinib, Encorafenib, and Cetuximab Combined to Treat BRAF-Mutant Colorectal Cancer) study demonstrated that a combination therapy consisting of BRAF, epidermal growth factor receptor, and mitogen-activated protein kinase kinase inhibitors could be a useful second-or third-line alternative. This review summarizes the current treatment strategies for BRAF-mutant mCRC.     

Circulating adhesion molecules in sera of asthmatic children before and after steroid therapy.

The aim of this study was to evaluate respiratory function tests, total eosinophil counts, serum immune globulin E (IgE), and serum concentrations of soluble intercellular adhesion molecule (sICAM)1, soluble vascular cell adhesion molecule (sVCAM) 1, and soluble P-selectin (sP-selectin) levels in the children with mild and/or moderate asthma before and 3 months after inhaled steroids and to determine whether adhesion molecule levels showed any difference between asthmatic and healthy children and whether these levels changed with disease activity. A total of 28 children with bronchial asthma and 24 children as a control group were included in the study. All of the patients in the study group were administered inhaled budesonide treatment. The patients were reevaluated 3 months later. Respiratory functions tests were performed and total eosinophil count and serum total IgE level were determined. Serum levels of sICAM-1, sVCAM-1, and sP-selectin were determined and skin-prick tests were performed. Significant difference paralleled to clinical improvement was found in the study group for respiratory function tests, total eosinophil count, serum IgE level, and sICAM-1 levels determined before and after the treatment. However, no significant difference was found for sP-selectin and sVCAM-1 levels before and after the treatment. The higher level of sICAM-1 before the treatment suggests that leukocyte-endothelial adhesion have a role in bronchial asthma, which is an inflammatory airway disease. Reduction in the level of sICAM-1 after the treatment may be related to the decreased inflammation in response to therapy. However, no strong relationships were found between the determinants representing the inflammation and respiratory function tests.     

Protease inhibitor therapy and fetal growth potential in HIV-positive women

Our objective was to test if protease inhibitors (PIs) increase the incidence of fetal growth restriction (FGR). Human immunodeficiency (HIV)-seropositive women were studied. At birth the neonatal weight percentile was assigned by predicted growth potential (GP), accounting for race, parity, weight, height, gestational age, birthweight, and gender (Gardosi, 1992). FGR was defined as GP < 10% percentile. Maternal age, CD4 count, viral load, weight gain, prenatal care, tobacco, alcohol, substance abuse, and PI use were related to FGR using chi-square and multiple regression analysis. Ninety-three of 191 women received PI. In these, FGR occurred in 27 (29%) compared with 15 (15.3%) in the non-PI group ( P = 0.02). Maternal CD4 count ( P < 0.0001) was the primary determinant, and smoking ( P = 0.037) was an independent cofactor for FGR (Nagelkerke r2 = 0.24). Twenty-six of 82 (31.7%) smokers had FGR, versus 16 of 109 (14.7%) of nonsmokers (odds ratio, 2.69; 95% confidence interval, 1.33 to 5.46; P = 0.005). After exclusion of the CD4 count, PI became a cofactor for FGR ( P = 0.021 and Nagelkerke r2 = 0.104). We concluded that maternal HIV status and smoking determine the risk for FGR. Although PIs increase the risk for FGR, this effect appears to depend on maternal disease severity.     

RETRACTED ARTICLE: Perinatal and first year outcomes of spontaneous versus assisted twins: a single center experience

OBJECTIVE: The aim is to compare naturally conceived twins with twins conceived by assisted reproductive techniques (ART) by means of perinatal outcome, behavioural patterns and psychomotor development. MATERIAL AND METHODS: Three hundred and five spontaneous and 119 assisted twins were compared in aspects of behavioural patterns, mental and psychomotor development, as well as maternal and gestational age, foetal presentation, birth weight, sex, Apgar scores, perinatal complications, delivery route, and admission to neonatal intensive care unit (NICU) RESULTS: Although the maternal age was higher in assisted twins, the mean gestational age and birth weight of assisted twins were significantly less than those of spontaneous twins. The assisted twins did not differ from the naturally conceived twins in aspects of presentation, Apgar scores, admission to NICU and perinatal complications. However, caesarean section rate and the delivery rate of male foetuses were significantly higher in assisted twins. During the first year of life, retardation in mental and psychomotor development was more pronounced in assisted twins. Also assisted twins experienced behavioural problems and difficulties in parent-child interactions more frequently. CONCLUSIONS: Although twins born to assisted pregnancies had significantly shorter duration of gestation and thus less birth weight, their perinatal outcome was similar to that of spontaneous twins. The mothers of assisted twins may be keener on getting intensive prenatal care, which might in turn help to diminish any possible maternal and foetal risks. However, assisted twins showed significantly retarded psychomotor and mental development and experienced problems with environmental factors more frequently during their first year.     

Response to controlled ovarian stimulation and oocyte quality in women with myotonic dystrophy type I

Purpose In women the relationship between myotonic dystrophy type I and fertility remains controversial. The objective of this study was to evaluate the ovarian reserve, ovarian response to stimulation and oocyte quality in these patients. Materials and methods We compared 15 myotonic dystrophy type I patients with 39 age matched controls with isolated male factor infertility necessitating ICSI. Results All parameters of ovarian reserve (day 3 FSH and E2, antral follicle count and delta E2) were significantly better in the controls. Despite having significantly lower doses of gonadotrophin, the control group attained a higher number of retrieved oocyte–cumulus complexes (p < 0.04). Analysis of cytoplasmic and extracytoplasmic dysmorphism did not reveal any difference between the two groups. Fertilisation rate and top grade embryos on day 3 were similar in both groups. Conclusion The present study suggests that though women with myotonic dystrophy type I have a reduced ovarian reserve and respond poorly to controlled ovarian stimulation, there is no impact on oocyte and embryo quality. Hence suggesting that successful ART is feasible with appropriate selection in women with mild myotonic dystrophy. Capsule Women with myotonic dystrophy type I have reduced ovarian reserve and respond poorly to controlled ovarian stimulation, though there is no impact on oocyte quality.     

The correlation of plasma homocysteine with insulin resistance in polycystic ovary syndrome

AIM: This study aims to investigate the existence of any relationship between homocysteine levels and insulin resistance in Turkish women with polycystic ovary syndrome. METHODS: A case-controlled, cross-sectional, observational study was undertaken in a total of 94 infertile Turkish women who required professional help in the Department of Infertility of Dr Zekai Tahir Burak Women's Health Research and Education Hospital. The correlation between serum homocysteine with age, body mass index, hormone profile, fasting insulin and glucose concentrations and insulin resistance were examined in patients with polycystic ovary syndrome and the results were compared to those of women with normal ovaries, who served as a control group. RESULTS: The mean serum fasting glucose and insulin levels, thus insulin resistance index of women with polycystic ovary syndrome, were significantly higher than those of the control subjects. The mean serum homocysteine levels were significantly higher in women with polycystic ovary syndrome than those in the control group. A positive correlation was detected between the mean homocysteine, the insulin resistance index determined by homeostasis model assessment and the fasting insulin levels in polycystic ovary syndrome patients. CONCLUSIONS: Serum homocysteine levels are elevated in women with polycystic ovary syndrome, and this elevation is associated with the serum insulin level rather than androgen excess. The intense treatment of hyperhomocysteinemia in women with polycystic ovary syndrome might improve reproductive outcome and contribute to protection from cardiovascular risks.     

Comparison of Adhesive Properties of Five Different Prosthetic Materials Used in Hernioplasty

This experimental study was designed to assess and to compare intra-abdominal adhesions following the use of five commercially available prosthetic mesh grafts in the repair if abdominal wall defects. Sixty Wistar albino rats were randomly divided into six groups (n = 10). A 2 × 1 cm defect at abdominal wall was created and defects were closed either primarily or with one of the following prosthetic mesh grafts: monofilament polypropylene, polytetrafluoroethylene, sodium hyaluronate/carboxymethylcellulose-coated polypropylene, polypropylene/polyglactin 910 composite, or resorbable hydrophilic collagen-coated multifiber polyester. The severity of adhesions was graded, tensile strengths of adhesions were measured, and histopathological grades of inflammation and fibrosis were evaluated. Polypropylene mesh resulted in more adhesion formation in comparison to primary repair and other grafts used in this study, except polypropylene/polyglactin 910 composite mesh. In addition, the highest tensile strength of omental adhesions was detected in the polypropylene group (χ² = 26.249; p =. 0001). Polyester composite mesh caused the least adhesion formation among the groups. Sodium hyaluronate/carboxymethylcellulose-coated polypropylene and polyester composite meshes revealed the highest fibrosis scores (χ² = 50.776; p =. 0001). The highest inflammatory activity was detected in the polytetrafluoroethylene mesh group (χ² = 16.564; p =. 005). Thus, sodium hyaluronate/carboxymethylcellulose-coated polypropylene and polytetrafluoroethylene meshes following polyester composite mesh were the minimal adhesion-forming grafts in this study. Disadvantages of the polytetrafluoroethylene mesh were lower fibrotic activity and higher inflammatory reaction to the graft.     

Left Atrial Deformation Parameters Predict Left Atrial Appendage Function and Thrombus in Patients in Sinus Rhythm with Suspected Cardioembolic Stroke: A Speckle Tracking and Transesophageal Echocardiography Study

The aim of this study was to evaluate left atrial deformations using speckle tracking echocardiography for predicting left atrial appendage (LAA) thrombus in patients with suspected cardioembolic stroke who were in normal sinus rhythm. A total of 153 ischemic stroke patients (89 males, 64 females) in sinus rhythm who were suspected of having cardioembolism were included in the study. The patients underwent conventional two‐dimensional (2D) echocardiogram and 2D speckle tracking echocardiogram of the left atrium. Left atrial peak strain (LA‐4C‐RES) and left atrial precontraction strain (LA‐4C‐PUMP) were measured. Patients were divided into 2 groups according to the presence of thrombus in the LAA in transesophageal echocardiography. Both LA‐4C‐RES and LA‐4C‐PUMP values were found to be significantly lower in patients with LAA thrombus (11.8 ± 1.4% vs. 33 ± 12%, P < 0.001 and 5.8 ± 1.3% vs. 14.2 ± 5.3%, P < 0.001, respectively). A good inverse correlation was present between LA‐4C‐RES values and LAA morphologic parameters (with LAA area: r = ?0.70, P < 0.001, with LAA length: r = ?0.60, P < 0.001), and a good positive correlation was present with LAA emptying velocity with pulse Doppler (r = 0.74, P < 0.001). The area under the receiver‐operating characteristic curve of the LA‐4C‐RES was 0.94 (0.90–0.98, P < 0.001), for the LA‐4C‐PUMP, the area was 0.92 (0.87–0.96, P < 0.001) to predict LAA thrombus. Left atrial deformation parameters measured by 2D speckle tracking method was found to predict impaired LAA functions and the presence of LAA thrombus in ischemic stroke patients with suspected cardioembolism, but who are in sinus rhythm.