Evaluation of pseudoprogression in patients with glioblastoma multiforme using dynamic magnetic resonance imaging with ferumoxytol calls RANO criteria into question

Background

Diagnosis of pseudoprogression in patients with glioblastoma multiforme (GBM) is limited by Response Assessment in Neuro-Oncology (RANO) criteria to 3 months after chemoradiotherapy (CRT). Frequency of pseudoprogression occurring beyond this time limit was determined. Survival comparison was made between pseudoprogression and true progression patients as determined by using perfusion magnetic resonance imaging with ferumoxytol (p-MRI-Fe).

Methods

Fifty-six patients with GBM who demonstrated conventional findings concerning for progression of disease post CRT were enrolled in institutional review board-approved MRI protocols. Dynamic susceptibility-weighted contrast-enhanced p-MRI-Fe was used to distinguish true progression from pseudoprogression using relative cerebral blood volume (rCBV) values. rCBV of 1.75 was assigned as the cutoff value. Participants were followed up using RANO criteria, and survival data were analyzed.

Results

Twenty-seven participants (48.2%) experienced pseudoprogression. Pseudoprogression occurred later than 3 months post CRT in 8 (29.6%) of these 27 participants (ie, 8 [14.3%] of the 56 patients meeting the inclusion criteria). Overall survival was significantly longer in participants with pseudoprogression (35.2 months) compared with those who never experienced pseudoprogression (14.3 months; P < .001).

Conclusions

Pseudoprogression presented after 3 months post CRT in a considerable portion of patients with GBM, which raises doubts about the value of the 3-month time limit of the RANO criteria. Accurate rCBV measurement (eg, p-MRI-Fe) is suggested when there are radiographical concerns about progression of disease in GBM patients, regardless of any time limit. Pseudoprogression correlates with significantly better survival outcomes.     

Design and implementation of a system for treating paediatric patients with stereotactically-guided conformal radiotherapy

Background and purpose: Stereotactically-guided conformal radiotherapy (SCRT) allows the delivery of highly conformal dose distributions to localised brain tumours. This is of particular importance for children, whose often excellent long-term prognosis should be accompanied by low toxicity. The commercial immobilisation system in use at our hospital for adults was felt to be too heavy for children, and precluded the use of anaesthesia, which is sometimes required for paediatric patients. This paper therefore describes the design and implementation of a system for treating children with SCRT. This system needed to be well tolerated by patients, with good access for treating typical childhood malignancies.

Materials and methods: A lightweight frame was developed for immobilisation, with a shell-based alternative for patients requiring general anaesthetic. Procedures were set up to introduce the patients to the frame system in order to maximise patient co-operation and comfort. Film measurements were made to assess the impact of the frame on transmission and surface dose. The reproducibility of the systems was assessed using electronic portal images.

Results: Both frame and shell systems are in clinical use. The frame weighs 0.6 kg and is well tolerated. It has a transmission of 92–96%, and fields which pass through it deliver surface doses of 58–82% of the dose at d_max, compared to 18% when no frame is present. However, the frame is constructed to maximise the availability of unobstructed beam directions. Reproducibility measurements for the frame showed a mean random error of 1.0±0.2 mm in two dimensions (2D) and 1.4±0.7 mm in 3D. The mean systematic error in 3D was 2.2 mm, and 90% of all overall 3D errors were less than 3.4 mm. For the shell system, the mean 2D random error was 1.5±0.2 mm.

Conclusions: Two well-tolerated immobilisation devices have been developed for fractionated SCRT treatment of paediatric patients. A lightweight frame system gives a wide range of possible unobstructed beam directions, although beams that intersect the frame are not precluded, provided that output corrections are applied. A shell system allows the use of general anaesthesia. Both systems give reproducible immobilisation to complement the high-precision treatment delivery.     

HIV,HTLV, and Hepatitis B and C Infection in Blood Donors in Bahia,Brazil from 2008 to 2017

Although blood transfusion is an important therapeutic resource, transfusion-transmitted infections (TTIs) are still a cause for concern. Measures to mitigate this risk involve improvement of donor screening criteria and improvements in laboratory tests, especially the use of nucleic acid test (NAT). In this retrospective study we evaluated HIV, HTLV, HCV and HBV infection rates in blood donors of the Hematology and Hemotherapy Foundation of Bahia (Hemoba), Brazil, through serological and NAT results and the characteristics of donors. From February/2008 to December/2017, 777,446 blood donations were made. Most donors were male, aged 25–44 years, black and mixed race, and single or divorced. The density-type incidence (DTI; per 100,000) for each virus was 91.1 for HBV; 66.5 for HCV; 54.3 for HIV; and 33.9 for HTLV, with a decreasing trend observed over the period studied, except in the last biennium. NAT detected only 1 donor in immunological window for HIV (0.46/100,000 donations) and 3 donors in immunological window for HBV (1.8/100,000 donations). Serological positivity for all viruses studied was higher in the metropolitan region of Salvador, the state capital. Conclusion: DTI rates show a decreasing trend over the years studied, with a predominance of HBV infection. NAT allowed the detection of donors in immunological window periods, having an important role in improving transfusion safety.     

Development of alcohol control law,Sao Tome and Principe

The World Health Organization (WHO) African Region is struggling with increasing harm associated with alcohol consumption. Legislators of Sao Tome and Principe, concerned about this harm and the high prevalence of alcohol use disorders, designed a comprehensive alcohol control bill to tackle this situation. Input into the design of the bill was obtained through interviews involving many stakeholders. The process had five phases: (i) scoping the problem to understand the social burden of the harm caused by alcohol consumption; (ii) updating the evidence on alcohol policies and identifying areas for legislative interventions; (iii) drafting the bill; (iv) aligning the legislative framework of the bill; and (v) initiating the parliamentary procedure. The new bill scored 92/100 using a standardized alcohol control policy scale. The bill covers all domains of WHO’s 2010 global strategy to reduce the harmful use of alcohol, and includes the three most cost-effective interventions for reducing alcohol consumption: increased excise taxes on alcohol; bans or comprehensive restrictions on exposure to alcohol advertising; and restrictions on the availability of retailed alcohol through reduced hours of sale. The National Assembly plenary session upheld the bill, which is now under evaluation of the specialized First Commission on Political, Legal, Constitutional and Ethical Affairs. Approval of the bill requires the final voting once it is back with the National Assembly and its promulgation by the President. Drafting an alcohol control bill which is country-led, inclusive, evidence-based and free of interference by the alcohol industry helps prioritize public health objectives over other interests.     

Flap lift for LASIK retreatment in eyes with myopia

PURPOSE: To analyze the results achieved with LASIK retreatment after lifting the original flap in a large series of patients. DESIGN: Retrospective, noncomparative, interventional consecutive case series. PARTICIPANTS: Two thousand four hundred twenty-two consecutive eyes undergoing LASIK surgery for myopia, including 334 eyes submitted to flap lift for LASIK retreatment. MAIN OUTCOME MEASURES: Uncorrected visual acuity, best-corrected visual acuity, refractive error, and complications. RESULTS: LASIK retreatment was performed in 334 eyes (14%), and the mean time between initial procedure and retreatment was 8.2+/-6.2 months. The mean spherical equivalent (SE) improved from -1.2+/-0.6 diopters (D) (range, -4.2 to +1.2 D) before retreatment to +0.2+/-0.4 D (range, -3.1 to +1.1 D) after the retreatment. The uncorrected visual acuity (UCVA) after retreatment was 20/20 or better in 58% and 20/40 or better in 92% of eyes. The mean SE was within +/-1.0 D in 96% of the patients and within +/-0.5 D in 80.5% after retreatment. Eighteen eyes (5%) lost 1 line of best-corrected visual acuity, and 4 eyes (1%) lost 2 lines. CONCLUSIONS: LASIK retreatment surgery performed by relifting the flap was a useful procedure for correcting residual refractive errors after the primary LASIK procedure. It provided good uncorrected visual acuity, predictable results, good refractive stability, and few complications.     

Isoflavone, polymorphisms in estrogen receptor genes and breast cancer risk in case-control studies in Japanese, Japanese Brazilians and non-Japanese Brazilians

Epidemiologic studies have shown an inverse association between isoflavones and breast cancer risk. Because isoflavones bind estrogen receptors, we hypothesized that polymorphisms in the estrogen receptor genes might modify the association between isoflavone intake and breast cancer risk. We conducted hospital-based case-control studies of patients aged 20–74 years with primary, incident, histologically confirmed invasive breast cancer, and matched controls from among medical checkup examinees in Nagano, Japan, and from cancer-free patients in São Paulo, Brazil. A total of 846 pairs (388 Japanese, 79 Japanese Brazilians and 379 non-Japanese Brazilians) completed validated food frequency questionnaires, and provided blood samples. Five single nucleotide polymorphisms in the estrogen receptor alpha (rs9340799, rs1913474, and rs2234693) and beta (rs4986938 and rs1256049) genes were genotyped. We found no consistent association between the five single nucleotide polymorphisms and breast cancer risk among the three populations. In analyses of combinations of isoflavone intake and single nucleotide polymorphisms, an inverse association between intake and risk was limited to women with the GG genotype of the rs4986938 polymorphism for postmenopausal Japanese (odds ratio for highest versus lowest tertile = 0.47; P for trend = 0.01), Japanese Brazilians (odds ratio for highest versus lowest median = 0.31) and non-Japanese Brazilians (odds ratio for consumers versus non-consumers = 0.37) ( P for interaction = 0.11, 0.08, and 0.21, respectively). We found no remarkable difference for the other four polymorphisms. Our findings suggest that polymorphisms in the estrogen receptor beta gene may modify the association between isoflavone intake and breast cancer risk. ( Cancer Sci 2009; 100: 927–933)     

Serum S100B protein is increased in fasting rats

BACKGROUND: S100B is a calcium-binding protein expressed and secreted by astrocytes; serum and cerebrospinal fluid (CSF) S100B elevation has been proposed as an index of brain damage. However, other tissues are shown to produce this protein and the clinical significance of serum S100B elevation has been discussed. METHODS: We investigated the levels of serum and CSF S100B in fasting Wistar rats. Animals were divided into two groups, control and fasting for 48 h, and S100B levels in serum and CSF were determined by ELISA. S100B secretion in dissociated epididymal fat cells was investigated in the presence of epinephrine. RESULTS: We observed a significant >2-fold increase of S100B levels in serum of fasting rats, without changes in its CSF content. Moreover, we demonstrated in vitro epinephrine stimulated S100B release from fat cells. CONCLUSIONS: Present results reinforce that extracerebral sources of S100B, particularly adipocytes, contribute to its serum levels and support the idea that caution is needed when interpreting serum S100B increase as a clinical marker of brain damage.