Diffusion weighted imaging in early prediction of neoadjuvant chemotherapy response in breast cancer

Background

Neoadjuvant chemotherapy (NAC) has clinically important outcome. Early evaluation of the treatment response is important to avoid unnecessary therapy in non-responders. MRI is the most sensitive imaging for monitoring NAC response.

Prognostic Value of Prepro-Gastrin Releasing Peptide in Lung Cancer Patients; NCI-Prospective Study

Background: Prior series investigated the expression of prepro-gastrin releasing peptide (prepro-GRP) in the peripheral blood of lung cancer patients. Our aim was to assess any prepro-GRP role as a prognostic factor for small cell lung cancer (SCLC) and NSCLC and correlations with clinical presentation and treatment outcome. Methods: A prospective study was conducted during the time period from the beginning of January 2012 till the end of January 2014. Prepro-GRP expression was analysed using a nested RT-PCR assay in peripheral blood of 62 untreated lung cancer patients attending the National Cancer Institute (NCI), Cairo University, and 30 age and sex matched healthy volunteers. Results: Among the 62 lung cancer cases, there were 24 (38.7%) SCLC, and 38 (61.3%) NSCLC (10 squamous cell carcinomas, 12 adenocarcinomas, 11 large cell carcinomas, 4 undifferentiated carcinomas, and 1 adenosquamous carcinoma). Twenty six patients (41.9%) were prepro-GRP positive. Prepro-GRP expression was higher (58.3%) among SCLC patients compared to NSCLC (squamous cell carcinoma (15.4%), large cell carcinoma (36.4%), and adenocarcinoma (25%)). Mean OS among prepro-GRP negative cases was longer than that among preprogastrin positive cases (17.6 vs 14.9 months). The mean PFS durations among preprogastrin negative versus positive cases were 7.7 vs 4.6 months (p= 0.041). No difference in response to chemotherapy was identified between the groups (p=0.983). Conclusion: Prepro-GRP is suggested to be a useful prognostic marker for lung cancer patients, especially with the fast- growing, bad prognostic SCLC type. More studies should aim at detailed understanding of the mechanisms of prepro-GRP action and its use in monitoring the response to treatment in a larger cohort.     

An in vitro and in vivo evaluation of bioactive titanium implants following sodium removal treatment

ObjectiveThe aim of this study was to evaluate the effect of dilute HCl as a sodium removal treatment of grit blasted/NaOH/heat treated cp titanium implants on the in vitro bioactivity and the in vivo interface shear resistance at different healing periods.MethodsCylindrical implants were machined from cp titanium bars. Half of the implants were blasted by AL₂O₃ particles followed NaOH/heat treatment. The other half received similar treatment except, dilute HCl was additionally used as a sodium removal treatment. Implants surfaces topography was characterized by AFM before and after immersion in simulated body fluid (SBF) for 3 and 7 days. The implants resistance to interfacial shear force was evaluated at 2, 4, and 8 weeks implantation periods in experimental rabbits.ResultsSodium removal treatment significantly increased surface roughness (Sa parameter), valley fluid retention index and surface area before and after immersion in SBF, however, it significantly decreased core fluid retention index. Calcium and phosphorus containing surface deposits, of larger surface area, were precipitated on implants received the sodium removal treatment after 3 and 7 days in SBF. The implant–bone interface resistance to shear force was significantly increased at 2 weeks healing period after the use of the sodium removal treatment.SignificanceThe sodium removal treatment showed to be effective in improving the early bone–implant interface resistance to shear force. Topographical changes, after dilute HCl etching, seem to contribute to the different in vitro and/or in vivo responses observed.     

Probing nano-scale adhesion force between AFM and acid demineralized intertubular dentin: Moist versus dry dentin

Objective

The aim of this study was to investigate the effect of dentin dryness on the variation in the probed nano-scale adhesion force between an AFM silicon nitride tip and demineralized intertubular dentin collagen fibrils network surface.

Methods

Dentin specimens were etched with 37% phosphoric acid for 15 s and then divided into three groups. Specimens of the first two groups were air-dried for 5 or 10 s (DH5s and DH10s), respectively, whereas specimens of the third group were left in the hydrated condition (H). For each group, Force curves were characterized by contact-mode AFM and the adhesion force (Fad) was calculated. The structure of the demineralized collagen fibrils network was characterized by tapping mode AFM. The tensile bond strength (TBS) to dentin was evaluated using one alcohol-based dentin self-priming adhesive. The dentin/resin interface was investigated by SEM.

Results

Dentin specimens in the wet-hydrated condition (H) showed significantly higher adhesion force and TBS values than dry-dehydrated specimens (DH5s and DH10s). AFM images showed open collagen fibrils network structure in wet-hydrated specimens (H), while the dry-dehydrated specimens (DH5s and DH10s) showed a collapsed appearance to varying degrees. SEM images revealed minimum resin infiltration in dry-dehydrated specimens.

Significance

The nano-scale adhesion force between the AFM probe and demineralized intertubular dentin surface was shown to be sensitive to surface air-drying. The decrease in the nano-scale adhesion force with the increase in the time of air-dryness is related to dehydration of the demineralized collagen fibrils network surface.     

Analysis of common MEFV mutations in Egyptian patients with familial Mediterranean fever: molecular characterisation of the disease

Familial Mediterranean fever (FMF) is a hereditary inflammatory disorder transmitted as an autosomal recessive trait. It predominantly affects people living in, or originating from, areas around the Mediterranean and was difficult to diagnose until mutations in the MEFV gene were identified. This study aims to analyse the five most common MEFV mutations in Egyptian patients diagnosed clinically as FME Thirty-eight unrelated patients were tested for the presence of the MEFV gene mutations V726A, M694V, M694I, M680I and E148Q, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the amplification refractory mutation system (ARMS). Twenty-three patients (60.5%) had one or more mutations, whereas no mutation was found in the remaining 15 patients (39.5%). The most common mutation was M694I (42.5%), followed by V726A (22.5%), M680I (17.5%) and E148Q (17.5%). The M694V mutation was not detected. The profile of MEFV gene mutations in this study suggests that the origin of FMF in Egypt is heterogeneous, a finding in concordance with that for other Arab populations; however, some differences were observed as M694V, the most common mutation reported in Arabs, was not detected in this study.     

Sodium hypochlorite as dentin pretreatment for etch-and-rinse single-bottle and two-step self-etching adhesives: atomic force microscope and tensile bond strength evaluation

PURPOSE: The aim of this study was to evaluate the effect of using 5.25% commercial sodium hypochlorite treatment prior to the application of etch-and-rinse and self-etching adhesives on dentin surface microtopography and tensile bond strength. MATERIALS AND METHODS: Thirty-two noncarious, nonrestored human third molars were collected. The occlusal enamel of all teeth was removed using diamond disks to expose flat dentin surfaces. The exposed dentin surfaces were abraded using 600-grit SiC disks, to create a uniform dentin smear layer. For AFM characterization, 12 teeth were equally divided into 4 groups according to the proposed dentin surface treatment. Three dentin disks, 2 mm thick, were evaluated per group using tapping mode assessment. Twenty teeth were used for TBS and SEM evaluation and were equally divided into 4 groups, according to the proposed dentin surface treatment. For TBS, 8 dentin/composite slabs, 2 mm thick, were used in each group, while for SEM evaluation 2 slabs were used. Each slab was tested in tension at a crosshead speed of 0.5 mm/min until failure occurred. The samples were examined using SEM operated at 30 kv to evaluate the hybrid layer photographically at 1500X. Statistical analysis was carried out using StatsDirect 2.5.7. One-way ANOVA followed by Tukey-Kramer multiple-comparison post-hoc tests were performed to test the difference between roughness parameters and TBS between groups. RESULTS: Sodium hypochlorite followed by the application of 37% phosphoric acid significantly increased the arithmetic average of the absolute values of surface height deviations (Sa), the surface area ratio which expresses the ratio between the surface area (taking the z height into account) and the area of the flat x,y plane (Sdr), and the surface bearing index (Sbi) parameters, while the application of sodium hypochlorite prior to the application of the self-etching primer significantly increased the valley fluid retention index (Svi) parameter. Self-etching primer without sodium hypochlorite pretreatment significantly increased the core fluid retention index (Sci) parameter. Sodium hypochlorite/AdheSE (7.42 +/- 2.16 MPa) significantly increased TBS value compared to other groups. However, no statistically significant difference was found between sodium hypochlorite/Excite (4.68 +/- 1.26 MPa), AdheSE (4.42 +/- 1.36), and Excite (4.06 +/- 1.35). Remnants of smear layer were detected with areas devoid of resin tags in SEM images of samples bonded with AdheSE self-etching adhesive, in contrast to samples bonded with sodium hypochlorite followed by AdheSE self-etching adhesive. CONCLUSION: The application of 5.25% commercial sodium hypochlorite with rubbing action for 60 s (total application time 120 s) seems to positively influence the TBS of the self-etching adhesive; however, it has no significant effect on TBS of etch-and-rinse single-bottle adhesive to dentin. The addition of functional roughness parameters to study the dentin surface was shown to be of importance in evaluating the relationship between bond strength and surface topography of conditioned dentin.     

Sleep–wake functioning along the cancer continuum: focus group results from the Patient‐Reported Outcomes Measurement Information System (PROMIS®)

Objective: Cancer and its treatments disturb sleep–wake functioning; however, there is little information available on the characteristics and consequences of sleep problems associated with cancer. As part of an effort to improve measurement of sleep–wake functioning, we explored the scope of difficulties with sleep in a diverse group of patients diagnosed with cancer. Methods: We conducted 10 focus groups with patients recruited from the Duke University tumor registry and oncology/hematology clinics. Separate groups were held with patients scheduled to begin or currently undergoing treatment for breast, prostate, lung, colorectal, hematological, and other cancer types and with patients who were in posttreatment follow‐up. The content of the focus group discussions was transcribed and analyzed for major themes by independent coders. Results: Participants not only reported causes of sleep disturbance common in other populations, such as pain and restless legs, but they also reported causes that may be unique to cancer populations, including abnormal dreams, anxiety about cancer diagnosis and recurrence, night sweats, and problems with sleep positioning. Many participants felt that sleep problems reduced their productivity, concentration, social interactions, and overall quality of life. Many also shared beliefs about the increased importance of sleep when fighting cancer. Conclusions: The findings underscore the need for interventions that minimize the negative impact of cancer and its treatments on sleep. This study will inform efforts now underway to develop a patient‐reported measure of sleep–wake functioning that reflects the breadth of concepts considered important by patients with cancer. Copyright © 2009 John Wiley & Sons, Ltd.     

Tumor necrosis factor-α and interleukin-6 in cirrhotic patients with spontaneous bacterial peritonitis

AIM: To evaluate the role of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in cirrhotic patients who have hepatic and renal impairment with spontaneous bacterial peritonitis (SBP).METHODS: We prospectively studied 120 cirrhotic patients with SBP and 80 cirrhotic patients with sterile ascitic fluid. They included 144 males and 56 females with ages ranging between 34 and 62 years. The diagnosis of cirrhosis was established by clinical and laboratory criteria that did not require histological confirmation. The severity of underlying liver disease was evaluated using Pugh’s modification of Child’s criteria (Child-Pugh scores). Ascitic fluid was sent to the laboratory for cell count, culture, sensitivity testing, and measurement of chemical elements (i.e., albumin, glucose). Specimens were inoculated into aerobic and anaerobic blood culture bottles. Serum and ascitic fluid were also collected in sterile tubes at study entry (before the initiation of antibiotic treatment) and 48 h later. Assays for TNF-α and IL-6 in the serum and ascitic fluid were performed with an immunoenzymometric assay using manufacture’s instructions.RESULTS: Cytokine levels in serum and ascitic fluid were significantly higher in the patients with SBP. (plasma TNF-α: 135.35 ng/mL ± 11.21 ng/mL vs 92.86 ng/mL ± 17.56 ng/mL, P < 0.001; plasma IL-6: 32.30 pg/mL ± 7.07 pg/mL vs 12.11 pg/mL ± 6.53 pg/mL, P < 0.001; ascitic fluid TNF-α: 647.54 ± 107.11 ng/mL vs 238.43 ng/mL ± 65.42 ng/mL, P < 0.001); ascitic fluid IL-6: 132.84 ng/mL ± 34.13 vs 40.41 ± 12.85 pg/mL, P < 0.001). About 48 (40%) cirrhotic patients with SBP developed renal and hepatic impairment and showed significantly higher plasma and ascitic fluid cytokine levels at diagnosis of infection. [(plasma TNF-α: 176.58 ± 17.84 vs 135.35 ± 11.21 ng/mL) (P < 0.001) and (IL-6: 57.83 ± 7.85 vs 32.30 ± 7.07 pg/mL) (P < 0.001); ascitic fluid TNF-α: 958.39 ± 135.72 vs 647.54 ± 107.11 ng/mL, (P < 0.001), ascitic fluid IL-6: 654.74 ± 97.43 vs 132.84 ± 34.13 pg/mL, (P < 0.001)]. Twenty nine patients (60.4%) with SBP and renal impairment died whereas, only four patients (5.55%) with SBP but without renal impairment died from gastrointestinal hemorrhage (P < 0.0005).CONCLUSION: It appears that TNF-α production may enhance liver cell injury and lead to renal impairment. This correlated well with the poor prognosis and significantly increased mortality associated with SBP in cirrhotic patients.