Definitive radiotherapy for early stage glottic cancer by 6 MV photons

Purpose: To evaluate the clinical outcome of early glottic cancer (GC) treated by primary radiotherapy (RT) with 6 MV photons. Methods and materials: We retrospectively reviewed the medical records of 695 consecutive patients with T1N0 and T2N0 GC treated between 1983 and 2005 by RT in our institution. Clinical outcome in terms of local control (LC), overall survival (OS) and cause- specific survival (CSS) rate were evaluated. Results: The median follow-up time was 10.5 years.The 10-year actuarial LC rates were as follows: T1A, 91%; T1B, 87%; T2, 77%. The 10-year OS were as follows: T1, 74.2%; T2, 70.7%. The 10-year CSS were as follows: T1, 97.7%; T2, 97.1%. Poorly differentiated histology and tumor biologically effective dose < 65 Gy.© 2012 Tong et al.; licensee BioMed Central Ltd.Link_to_subscribed_fulltex

A Gramaticalização do Verbo Ir e a Variação de Formas para Expressar o Futuro do Presente: uma Fotografia Capixaba

Esta pesquisa verifica o estágio do processo de gramaticalização do verbo IR, que tem assumido a função de auxiliar em construções perifrásticas para expressar tempo. Para isso, investiga-se a variação entre as formas sintética e perifrástica com IR para expressão do futuro do presente. Temos por hipótese que a forma perifrástica já atinge todos os gêneros das duas modalidades da língua, uma vez que já se especializou para codificar tempo. São examinados dois gêneros, tomando-os como prototípicos do continuun oral/escrito: entrevistas com informantes universitários e editoriais de jornal. Partindo de uma orientação teórica Funcionalista, num quadro mais geral, concebe-se a língua como flexível ao uso, passível de influências cognitivas, sociais e também individuais, embora haja nela forças que atuam no sentido de regularizar a estrutura. Seguindo algumas pesquisas que têm se mostrado frutíferas, o modelo funcionalista estará em diálogo com outro modelo que procura dar conta da heterogeneidade estruturada da língua e de seus processos de mudança: a Teoria Variacionista. Num quadro mais específico, os fundamentos que orientam a pesquisa são os da Gramaticalização. Os dados extraídos dos gêneros selecionados serão submetidos ao programa computacional GOLDVARB 2001 e, em seguida, interpretados à luz das teorias lingüísticas que fundamentam esta pesquisa

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Clinical metabonomics for advanced laboratory medicine

Metabonomics is an unbiased and comprehensive quantitative study of metabolomes in a biological system. Using a metabonomics approach, new insight in disease pathogenesis and novel diagnostic biomarkers with improved accuracy can be identified with clinical impact. This PhD study focused on clinical metabonomics in advanced laboratory medicine. In part I, it was focused on the biomarker discovery for urinary tract infection (UTI) using nuclear magnetic resonance (NMR)-based metabonomics. Urine acetic acid and trimethylamine (TMA) were determined to be the best biomarker for diagnosing bacterial and Escherichia coli (EC)-associated UTI respectively. The area-under-curve (AUC) for acetic acid was 0.97 (95% confidence interval (CI): 0.94 – 1.00) and that for TMA was 0.85 (95% CI: 0.76 – 0.92). The performances were superior to conventional laboratory tests, i.e. dipstick urinalysis and urine microscopy. The high urine acetic acid was secondary to bacterial anaerobic respiration whereas TMA was a microbial-mammalian co-metabolite which was converted from trimethylamine N-oxide (TMAO), a human metabolite by EC TMAO reductase. In part II, the diagnostic application of acetic acid in bacterial UTI was extend to spontaneous bacterial peritonitis (SBP). Rapid diagnosis for SBP is vital because antibiotics treatment could dramatically reduce morbidity and mortality. Using NMR-based metabolomics approach, peritoneal fluid acetic acid was significantly elevated in SBP patients but undetected in controls. This finding echoed the results in part I and supported acetic acid as a biomarker for active bacterial infection. In part III, it was focused on the classification of pleural effusions (PE) using NMR-based metabonomics. PE lipoprotein was determined to be the best biomarker to differentiate exudates from transudates with an AUC of 0.96 (95% CI: 0.89 – 0.99). The diagnostic performance was superior to the Light's criteria recommended by International guideline. Elevated lipoprotein in exudates was secondary to increased capillary pore-size of the inflamed pleura. Therefore, quantification of PE lipoprotein will help assessing disease severity which is a novel and only clinical test for in vivo pleural permeability measurement. To determine the aetiology of exudates, liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based metabonomics was applied for cancerous and tuberculous PE, the two major causes of exudates. High levels of PE oleic acid and ceramide (d18:1/16:0) were found in cancerous and tuberculous PE respectively. The high oleic acid was secondary to fatty acid synthase (FASN) over-expression in cancer cells while the high ceramide was secondary to host immune response. Using a ratio of the two to predict cancerous and tuberculous PE, the AUC was increased to 0.99 (95% CI: 0.91 – 1.00). In part IV, it was focused on the rapid diagnosis of inborn errors of metabolism (IEM) using NMR spectroscopy. Patients with IEM can present with acute metabolic decompensation. Currently, most clinical laboratories rely on gas chromatography-mass spectrometry (GC-MS) for the diagnosis of IEM which usually takes a considerable time, i.e. day(s). The feasibility of NMR spectroscopy as a rapid diagnostic test was evaluated using various IEM conditions. Pathognomonic metabolites were identified using NMR-based urinalysis in <15 minutes. This supports the essential clinical role of NMR spectroscopy for rapid diagnosis of IEM.published_or_final_versionPathologyDoctoralDoctor of Philosoph

Emphysematous pyelonephritis: An 8-year retrospective review across four acute hospitals

To retrospectively review our experience of managing patients with emphysematous pyelonephritis (EPN). Case notes of patients with EPN were reviewed. The patients' demographic data, clinical presentation, investigation findings, treatment, and outcome were studied. Twelve patients were diagnosed with EPN. Majority (66.7%) of them had diabetes mellitus. All patients had been evaluated by computed tomography (CT). Using the classification proposed by Wan et al, five patients had type 1 EPN, whereas six, two, and four patients had Huang and Tseng CT class 2, 3a, and 3b EPN, respectively. Immediate nephrectomy was performed in six patients, whereas conservative treatment was adopted in the other six. In the nephrectomy group, one patient died of disseminated sepsis after a protracted course. Conservative treatment failed in three patients, who succumbed despite salvage nephrectomy in two of them. Analysis revealed that severe hyperglycemia and radiological CT class (both Wan and Huang systems) were significant predictors of mortality from EPN. Severe hyperglycemia and CT class of EPN are significant risk factors for death. CT is the investigation of choice for correct diagnosis of EPN. Additional intervention should be offered to EPN patients with Wan type 1 and Huang and Tseng class 3 CT features

Emphysematous pyelonephritis: An 8-year retrospective review across four acute hospitals

Objective: To retrospectively review our experience of managing patients with emphysematous pyelonephritis (EPN). Methods: Case notes of patients with EPN were reviewed. The patients' demographic data, clinical presentation, investigation findings, treatment, and outcome were studied. Results: Twelve patients were diagnosed with EPN. Majority (66.7%) of them had diabetes mellitus. All patients had been evaluated by computed tomography (CT). Using the classification proposed by Wan et al, five patients had type 1 EPN, whereas six, two, and four patients had Huang and Tseng CT class 2, 3a, and 3b EPN, respectively. Immediate nephrectomy was performed in six patients, whereas conservative treatment was adopted in the other six. In the nephrectomy group, one patient died of disseminated sepsis after a protracted course. Conservative treatment failed in three patients, who succumbed despite salvage nephrectomy in two of them. Analysis revealed that severe hyperglycemia and radiological CT class (both Wan and Huang systems) were significant predictors of mortality from EPN. Conclusion: Severe hyperglycemia and CT class of EPN are significant risk factors for death. CT is the investigation of choice for correct diagnosis of EPN. Additional intervention should be offered to EPN patients with Wan type 1 and Huang and Tseng class 3 CT features

Clinical whole-exome sequencing reveals a common pathogenic variant in patients with CoQ10 deficiency: An underdiagnosed cause of mitochondriopathy

[Background]: Primary CoQ deficiency occurs because of the defective biosynthesis of coenzyme Q, one of the key components of the mitochondrial electron transport chain. Patients with this disease present with a myriad of non-specific symptoms and signs, posing a diagnostic challenge. Whole-exome sequencing is vital in the diagnosis of these cases.[Case]: Three unrelated cases presenting as either encephalopathy or cardiomyopathy have been diagnosed to harbor a common pathogenic variant c.370G > A in COQ4. COQ4 encodes a key structural component for stabilizing the multienzymatic CoQ biosynthesis complex. This variant is detected only among East and South Asian populations.[Conclusions]: Based on the population data and our case series, COQ4-related mitochondriopathy is likely an underrecognized condition. We recommend including the COQ4 c.370G > A variant as a part of the screening process for mitochondriopathy in Chinese populations.This work was supported by the S.K. Yee Medical Foundation, Hong Kong

Harnessing Next-Generation Sequencing as a Timely and Accurate Second-Tier Screening Test for Newborn Screening of Inborn Errors of Metabolism

In this study, we evaluated the implementation of a second-tier genetic screening test using an amplicon-based next-generation sequencing (NGS) panel in our laboratory during the period of 1 September 2021 to 31 August 2022 for the newborn screening (NBS) of six conditions for inborn errors of metabolism: citrullinemia type II (MIM #605814), systemic primary carnitine deficiency (MIM #212140), glutaric acidemia type I (MIM #231670), beta-ketothiolase deficiency (#203750), holocarboxylase synthetase deficiency (MIM #253270) and 3-hydroxy-3-methylglutaryl-CoA lyase deficiency (MIM # 246450). The custom-designed NGS panel can detect sequence variants in the relevant genes and also specifically screen for the presence of the hotspot variant IVS16ins3kb of SLC25A13 by the copy number variant calling algorithm. Genetic second-tier tests were performed for 1.8% of a total of 22,883 NBS samples. The false positive rate for these six conditions after the NGS second-tier test was only 0.017%, and two cases of citrullinemia type II would have been missed as false negatives if only biochemical first-tier testing was performed. The confirmed true positive cases were citrullinemia type II (n = 2) and systemic primary carnitine deficiency (n = 1). The false positives were later confirmed to be carrier of citrullinemia type II (n = 2), carrier of glutaric acidemia type I (n = 1) and carrier of systemic primary carnitine deficiency (n = 1). There were no false negatives reported. The incorporation of a second-tier genetic screening test by NGS greatly enhanced our program’s performance with 5-working days turn-around time maintained as before. In addition, early genetic information is available at the time of recall to facilitate better clinical management and genetic counseling