Brief Report: Prognostic Relevance of 3q Amplification in Squamous Cell Carcinoma of the Lung

INTRODUCTION: Amplification of 3q is the most common genetic alteration identified in squamous cell carcinoma of the lung (LUSC), with the most frequent amplified region being 3q26 to 3q28. METHODS: In this analysis, we aim to describe the prognostic relevance of 3q amplification by focusing on a minimal common region (MCR) of amplification constituted of 25 genes. We analyzed 511 cases of LUSC from The Cancer Genome Atlas and included 476 in the final analysis. RESULTS: We identified a 25-gene MCR that was amplified in 221 (44.3%) cases and was associated with better disease-specific survival (not reported [NR] versus 9.25 y, 95% confidence interval [CI]: 5.24-NR, log-rank p = 0.011) and a progression-free interval of 8 years (95% CI: 5.1-NR) versus 4.9 years (95% CI: 3.5-NR, log-rank p = 0.020). Multivariable analysis revealed that MCR amplification was associated with improved disease-specific survival and progression-free interval. CONCLUSIONS: Amplification of the 25-gene MCR within 3q was present in 44% of this cohort, consisting mainly of Caucasian patients with early stage LUSC. This analysis strongly indicates the prognostic relevance of the 25-gene MCR within 3q. We are further evaluating its prognostic and predictive relevance in a racially diverse patient population with advanced LUSC

Potential role of BRCA1 protein expression as a prognostic tissue biomarker in breast carcinoma: An immunohistochemical and clinicopathologic study from South India

Introduction. BRCA1 dysfunction is a hallmark of both hereditary and sporadic breast cancer. BRCA1 protein expression can be lost by germline mutation, somatic mutation or promoter hypermethylation. This study aimed to explore BRCA1 dysfunction in breast cancer patients by immunohistochemistry and to study its association with prognostic factors. Material and methods. BRCA1 protein expression was assessed by immunohistochemistry on formalin fixed paraffin embedded tissue blocks of 110 invasive breast carcinoma patients. Furthermore, the clinical findings and tumor features associated with BRCA1 dysfunction were characterized. Results. Reduced BRCA1 immunoreactivity was observed in 19% of breast cancer cases. Although these patients presented with aggressive tumor characteristics, statistical significance was observed only with presence of lymphovascular emboli (p < 0.05). These results suggest that loss of BRCA1 protein expression is associated with an aggressive phenotype of breast carcinoma. Conclusions. Immunohistochemistry for BRCA1 protein expression in tumor tissues may provide a less expensive screening tool to identify BRCA1 dysfunction due to genetic or epigenetic alterations

Mortality Among Adults With Cancer Undergoing Chemotherapy or Immunotherapy and Infected With COVID-19

Importance: Large cohorts of patients with active cancers and COVID-19 infection are needed to provide evidence of the association of recent cancer treatment and cancer type with COVID-19 mortality. // Objective: To evaluate whether systemic anticancer treatments (SACTs), tumor subtypes, patient demographic characteristics (age and sex), and comorbidities are associated with COVID-19 mortality. // Design, Setting, and Participants: The UK Coronavirus Cancer Monitoring Project (UKCCMP) is a prospective cohort study conducted at 69 UK cancer hospitals among adult patients (≥18 years) with an active cancer and a clinical diagnosis of COVID-19. Patients registered from March 18 to August 1, 2020, were included in this analysis. // Exposures: SACT, tumor subtype, patient demographic characteristics (eg, age, sex, body mass index, race and ethnicity, smoking history), and comorbidities were investigated. // Main Outcomes and Measures: The primary end point was all-cause mortality within the primary hospitalization. // Results: Overall, 2515 of 2786 patients registered during the study period were included; 1464 (58%) were men; and the median (IQR) age was 72 (62-80) years. The mortality rate was 38% (966 patients). The data suggest an association between higher mortality in patients with hematological malignant neoplasms irrespective of recent SACT, particularly in those with acute leukemias or myelodysplastic syndrome (OR, 2.16; 95% CI, 1.30-3.60) and myeloma or plasmacytoma (OR, 1.53; 95% CI, 1.04-2.26). Lung cancer was also significantly associated with higher COVID-19–related mortality (OR, 1.58; 95% CI, 1.11-2.25). No association between higher mortality and receiving chemotherapy in the 4 weeks before COVID-19 diagnosis was observed after correcting for the crucial confounders of age, sex, and comorbidities. An association between lower mortality and receiving immunotherapy in the 4 weeks before COVID-19 diagnosis was observed (immunotherapy vs no cancer therapy: OR, 0.52; 95% CI, 0.31-0.86). // Conclusions and Relevance: The findings of this study of patients with active cancer suggest that recent SACT is not associated with inferior outcomes from COVID-19 infection. This has relevance for the care of patients with cancer requiring treatment, particularly in countries experiencing an increase in COVID-19 case numbers. Important differences in outcomes among patients with hematological and lung cancers were observed

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

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

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

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Anaesthesia for Nesidioblastosisin A New Born: A Case Report

Congenital hyperinsulinism as seen in nesidioblastosis is the most common cause of non transient neonatal hypoglycaemia. The prime concern in nesidioblastosis is the prevention of dangerous hypoglycaemia which can lead to coma, brain damage or mental retardation. In this report we describe the presentation and perioperative course of a case of nesidioblastosis in a newborn who had persistent hypoglycaemia with convulsions in spite of high concen-trations of dextrose infusion. As sugars were low in spite of medical management, 95% pancreatectomy was done and the baby was discharged following discontinuation of intravenous fluids and starting breast feeds

Satisfaction of hem/onc patients with video visits during the COVID-19 pandemic at a tertiary care center in Michigan

Background: In early 2020, the WHO declared the COVID-19 pandemic a public health emergency. Consequently, medical institutions minimized health care services to facilitate social distancing and telemedicine became the forefront of patient-provider interaction. Herein, we present the results of our study that explored patient satisfaction with video visits during the pandemic at a tertiary care center. Methods: A 12-question survey (table) was emailed following a video visit with a Hem/Onc provider carried out between February and December 2020, questions were answered anonymously. The survey also collected patient demographics. The survey evaluated 5 aspects of telemedicine using a five-point graded scale. Results: A total of 1107 patients responded. Median age was 65 years (25-97) with 51.5% over 65, 64% were females and 36% males. Based on zip codes of primary residence and 2015-2019 US Census data, a significant proportion lived in inner-city Detroit, 77.3% were Caucasians, and 15.2% African Americans. Median household income was 66.8K (Michigan’s median is 57K). Regarding access: ease of scheduling appointments, ease of contacting the office and ability to schedule desired appointments, were respectively given positive responses (good, very good, or fair) by 97.61%, 97.32%, and 98.4%. Regarding CP: ability to explain problem, show concern for worries, include patients in decisions, and discussion of treatment plan, were respectively given positive responses by 99.09%, 99.26%, 98.9%, 99.35%. Regarding telemedicine technology: ease of talking to CP, quality of video, and audio connections, were respectively given positive responses by 94.27%, 90.77%, and 91.42%. For the overall visit assessment, 98.58% gave a positive response for the video staff performance. Regarding their comfort level to return to clinic: 78.75% were comfortable and 10.14% were not. Conclusions: Patients reported an overall high level of satisfaction with telemedicine. One area of improvement is the technological aspect. More than 50% were older than 65 years and a significant proportion lived in underserved areas which indicates that telemedicine is easily accessible. Moreover, around 80% were comfortable to return to clinic while 10% were not which highlights the importance of offering both telemedicine and in-person care