Treatment of Intractable Diabetic Macular Edema with Pegaptanib Versus Bevacizumab, Both in Combination with Dexamethasone

BACKGROUND: Diabetic macular edema is a significant cause of vision loss, and some patients do not respond optimally to existing treatments. This study compared the response of intractable diabetic macular edema to intravitreal injection of two anti-VEGF drugs, bevacizumab and pegaptanib, both in combination with dexamethasone. METHODS: A retrospective chart review was conducted to examine patients from an ophthalmology practice in one year with diabetic macular edema (DME), recurrent or persistent, after focal laser or intravitreal bevacizumab. Patients received bevacizumab/dexamethasone or pegaptanib/dexamethasone. Outcome measures were improvement in best corrected visual activity (converted to LogMAR) and central macular thickness (CRT). Data on adverse effects also were collected. RESULTS: The bevacizumab/dexamethasone group included 25 eyes which had pre-treatment LogMAR = 0.69 ± 0.49 (mean ± SD) and CRT = 419 ± 131. Post-treatment LogMAR was 0.70 ± 0.48 and CRT = 377 ± 107. The pegaptanib/dexamethasone group included 14 eyes; pretreatment LogMAR = 0.80 ± 0.55 and CRT = 520 ± 108. Post-treatment LogMAR was 0.77 ± 0.49 and CRT = 46 4 ± 106. Neither treatment had a significant effect on visual acuity. Both groups experienced a significant decrease in CRT over time (p = 0.006). The pegaptanib/ dexamethasone group had higher CRT at all times (p = 0.020), but the trend in CRT decrease was not different between the two groups. Intraocular pressure increased in both groups (p = 0.038). No other adverse effects were reported. CONCLUSIONS: Neither bevacizumab/dexamethasone or pegaptanib/dexamethasone significantly improved visual acuity in intractable DME, but both decreased central macular thickness. Differences in outcome measures between the two treatment groups were not significant. The only adverse effect seen was a small increase in intraocular pressure

Patterns of mandibular invasion in oral squamous cell carcinoma of the mandibular region

BACKGROUND: Mandibular resections are routinely carried out for achieving a R0 resection for oral cancers. However, the need of mandibular resection to achieve this has always been questioned. The present study was carried out to define the pattern of mandibular involvement in carcinoma of the mandibular region. PATIENTS AND METHODS: A total of 25 consecutive patients who had undergone mandibular resection and were found to have mandibular invasion were studied in a prospective open fashion. After decalcification the specimens were serially sectioned at 1 cm interval to identify invasion of mandibular bone. Type of invasion, route of spread and host cell reactions were also recorded. RESULTS: The mandibular involvement was infiltrative in 14(56%) and erosive in 11(44%). It was cortical in 5(20%), marrow involvement was seen in 15(60%) while 5(20%) had spread through the inferior alveolar canal. Of the 25, 24(96%) lesions were located with in 1 cm of the mandible. CONCLUSION: The possibility of mandibular involvement is higher in patients where tumours are located with in 1 cm of the mandible. Involvement of mandible through the canal of inferior alveolar nerve in the present study was relatively high (20%). Therefore it is recommended that before a decision is taken to preserve the mandible it should be thoroughly screened for possible involvement

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin with gemtuzumab ozogamicin improves event-free survival in younger patients with newly diagnosed aml and overall survival in patients with npm1 and flt3 mutations

Purpose To determine the optimal induction chemotherapy regimen for younger adults with newly diagnosed AML without known adverse risk cytogenetics. Patients and Methods One thousand thirty-three patients were randomly assigned to intensified (fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin [FLAG-Ida]) or standard (daunorubicin and Ara-C [DA]) induction chemotherapy, with one or two doses of gemtuzumab ozogamicin (GO). The primary end point was overall survival (OS). Results There was no difference in remission rate after two courses between FLAG-Ida + GO and DA + GO (complete remission [CR] + CR with incomplete hematologic recovery 93% v 91%) or in day 60 mortality (4.3% v 4.6%). There was no difference in OS (66% v 63%; P = .41); however, the risk of relapse was lower with FLAG-Ida + GO (24% v 41%; P < .001) and 3-year event-free survival was higher (57% v 45%; P < .001). In patients with an NPM1 mutation (30%), 3-year OS was significantly higher with FLAG-Ida + GO (82% v 64%; P = .005). NPM1 measurable residual disease (MRD) clearance was also greater, with 88% versus 77% becoming MRD-negative in peripheral blood after cycle 2 (P = .02). Three-year OS was also higher in patients with a FLT3 mutation (64% v 54%; P = .047). Fewer transplants were performed in patients receiving FLAG-Ida + GO (238 v 278; P = .02). There was no difference in outcome according to the number of GO doses, although NPM1 MRD clearance was higher with two doses in the DA arm. Patients with core binding factor AML treated with DA and one dose of GO had a 3-year OS of 96% with no survival benefit from FLAG-Ida + GO. Conclusion Overall, FLAG-Ida + GO significantly reduced relapse without improving OS. However, exploratory analyses show that patients with NPM1 and FLT3 mutations had substantial improvements in OS. By contrast, in patients with core binding factor AML, outcomes were excellent with DA + GO with no FLAG-Ida benefit

Cellular manifestations of human papillomavirus infection in laryngeal tissues

Background and Objectives: Although epidemiologic studies have suggested human papillomavirus (HPV) to be an etiological agent in laryngeal carcinogenesis, little is known on the cellular manifestations of HPV infection in these tumors. In this study, we investigated the frequency of HPV infection in various neoplastic and non-neoplastic laryngeal tissue and its association with expression of the proliferating cell nuclear antigen (PCNA) and the tumor suppressor protein p53. Methods: Tissues were analyzed by polymerase chain reaction (PCR) for the presence of HPV and by immunocytochemistry for the expression of p53 and PCNA. Results: None of the six normal laryngeal tissues showed the presence of HPV. Thirteen out of the 16 papillomas were positive for HPV, while 15 out of the 44 invasive cancers were HPV positive. PCNA expression increased as the lesion progressed through increasing histological abnormality (r=0.64400, P=0.00000). The correlation between the type of laryngeal neoplasm and p53 accumulation was significant (r=0.54839, P=0.00000). Significant correlation was also evident between presence of HPV and p53 accumulation (r=0.34259, P=0.00424) and PCNA expression (r=0.036024, P=0.00266) indicating that HPV positive tumors showed significant p53 accumulation and increased proliferation.There was also correlation between p53 and PCNA expression (r=0.67475, P=0.00000) indicating that in all tumors with p53 accumulation, there was a corresponding increase in PCNA expression. Conclusions: The results suggests that changes in p53 and PCNA expression may be associated with HPV infection, and could play a role in laryngeal carcinogenesis

Impact of retail industry service innovation and employee engagement on the marketing performance of modern trade in India

Modern commerce outlets are typically preferred by conglomerates of enterprises or chains of businesses. However, the performance of these company chains is hindered by a variety of issues that together harm them. According to the findings of the current research, the marketing performance of modern retail trade in India is significantly impacted by both the introduction of new services and the management of employees. As a result, the purpose of this study is to examine the impact that service innovation and staff engagement have on the overall marketing effectiveness of modern retail establishments. However, market orientation and consumer service performance act as mediators of the relationship between service innovation, employee engagement, and marketing performance. It has been observed that there is a direct relationship between service innovation, employee engagement, and marketing performance. The results of the present study were obtained by the collection of primary data through the administration of a survey to 370 marketing managers in India who are employed by a variety of brands, organizations, and businesses