169 research outputs found

    Histopathological diagnoses on pleural biopsy specimens over a 15-year period at Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa: A retrospective review

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    Background. Pleural effusions are a common reason for presentation to healthcare facilities. Blind closed pleural biopsy can be a useful tool to diagnose their cause, especially in resource-limited settings.Objectives. To determine the aetiology, frequency and change in profile of histopathological diagnoses made at Chris Hani Baragwanath Academic Hospital (CHBAH), Johannesburg, South Africa, over the period 1 January 2001 - 31 December 2015.Methods. Pleural biopsies performed at CHBAH and analysed by  histopathologists from the National Health Laboratory Service at the hospital over the study period were retrospectively reviewed by accessing reports from two databases (DISA and TrakCare). The subjects’ ages, genders, HIV status and histopathological diagnoses as well as adenosine deaminase and Ziehl-Neelsen results were recorded.Results. A total of 1 013 samples were included in the study, with 780 considered adequate for assessment. The most common diagnosis was granulomatous inflammation (48.1%, n=375), with the most common type being necrotising granulomatous inflammation (73.6%, n=276). Ten percent of biopsies (n=78) showed malignancy, most commonly  adenocarcinoma, with 46.2% (n=36) metastatic and 23.1% (n=18) primary lung adenocarcinoma. The odds of being diagnosed with malignancy  showed increasing statistical significance above the age of 40 years: 40 - 49 years odds ratio (OR) 8.7, 95% confidence interval (CI) 1.1 - 66.9 (p=0.038); 50 - 59 years OR 12.4, 95% CI 1.6 - 95.0 (p=0.015); ≥60 years OR 23.0, 95% CI 3.1 - 171.3 (p=0.002). HIV seropositivity was associated with lower odds of being diagnosed with malignancy compared with HIV-negative patients (OR 0.5, 95% CI 0.2 - 0.9; p=0.040), with greater odds of a ‘non-cancer’ diagnosis in HIV positive patients (including granulomatous inflammation and pleuritis (OR 2.16, 95% CI 1.03 - 4.51; p=0.040)).Conclusions. Blind closed pleural biopsy has a role to play in the diagnosis of exudative pleural effusions in resource-limited settings, particularly for patients suspected to have tuberculosis (TB) or malignancy. TB remains a common cause of exudative pleural effusions. Patients aged >40 years presenting with an exudative pleural effusion should routinely have pleural biopsy performed. However, this study showed a high  frequency of   inadequate specimens from closed pleural biopsy. Training in the   performance of this procedure to increase diagnostic rates is   recommended

    Evolution of gynaecologists' practices regarding the implementation of Swiss legislation on maternity protection at work between 2008 and 2017.

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    In accordance with the International Labour Organization’s Maternity Protection Convention (No. 183) and European Union Directive 92/857CEE (1992), Switzerland’s Labour Law and its Maternity Protection Ordinance (OProMa) aim to protect the health of pregnant employees and their future children while enabling them to pursue their working activities. Gynaecologists-obstetricians have a key role in this legislation, particularly through the prescription of preventive leave for patients who would otherwise face dangerous or arduous tasks in the absence of an adequate risk analysis or suitable protective measures. However, international and national literature suggests that gynaecologists-obstetricians may encounter difficulties in fulfilling their role. This study aimed to: (1) describe the practices and difficulties encountered by gynaecologists-obstetricians in the practical implementation of the OProMa; and (2) compare the evolution of these practices and difficulties between 2008 and 2017. A survey by questionnaire was conducted in 2008 and repeated in 2017. Both surveys focused on gynaecologists-obstetricians working in the French-speaking part of Switzerland (in private practices, hospitals or both). Descriptive and comparative analyses were carried out. 83 gynaecologists-obstetricians responded in 2008 and 93 in 2017: response rates of 47% and 32%, respectively. In 2017, gynaecologists-obstetricians were more likely to ask questions about occupational risks faced by their patients when consulted by working mothers about their pregnancies. The estimated percentage of patients exposed to an occupational risk remained constant (20% in 2008 and 22% in 2017). Communication and collaboration with employers were reported to be difficult in both surveys, even though these are key elements in the implementation of the OProMa. Collaboration with occupational physicians, however, was more frequent in 2017. In 2017, gynaecologists-obstetricians showed a greater awareness of occupational risks and collaborated more frequently with occupational health specialists. However, the application of the OProMa remained limited over the studied time period. Improving training of gynaecologists-obstetricians in this field could be a significant factor in encouraging better implementation of the current legislation. Moreover, gynaecologists-obstetricians need to be given the necessary support to enable their clinical practice to evolve towards a more preventive type of medicine. Collaboration with relevant stakeholders, including occupational physicians, midwives and workers, should be encouraged

    Evolution of active and polar photospheric magnetic fields during the rise of Cycle 24 compared to previous cycles

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    The evolution of the photospheric magnetic field during the declining phase and minimum of Cycle 23 and the recent rise of Cycle 24 are compared with the behavior during previous cycles. We used longitudinal full-disk magnetograms from the NSO's three magnetographs at Kitt Peak, the Synoptic Optical Long-term Investigations of the Sun (SOLIS) Vector Spectro-Magnetograph (VSM), the Spectromagnetograph and the 512-Channel Magnetograph instruments, and longitudinal full-disk magnetograms from the Mt. Wilson 150-foot tower. We analyzed 37 years of observations from these two observatories that have been observing daily, weather permitting, since 1974, offering an opportunity to study the evolving relationship between the active region and polar fields in some detail over several solar cycles. It is found that the annual averages of a proxy for the active region poloidal magnetic field strength, the magnetic field strength of the high-latitude poleward streams, and the time derivative of the polar field strength are all well correlated in each hemisphere. These results are based on statistically significant cyclical patterns in the active region fields and are consistent with the Babcock-Leighton phenomenological model for the solar activity cycle. There was more hemispheric asymmetry in the activity level, as measured by total and maximum active region flux, during late Cycle 23 (after around 2004), when the southern hemisphere was more active, and Cycle 24 up to the present, when the northern hemisphere has been more active, than at any other time since 1974. The active region net proxy poloidal fields effectively disappeared in both hemispheres around 2004, and the polar fields did not become significantly stronger after this time. We see evidence that the process of Cycle 24 field reversal has begun at both poles.Comment: Accepted for publication in Solar Physic

    Incidence, Risk Factors, and Outcomes of Patients Who Develop Mucosal Barrier Injury-Laboratory Confirmed Bloodstream Infections in the First 100 Days after Allogeneic Hematopoietic Stem Cell Transplant

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    Importance: Patients undergoing hematopoietic stem cell transplant (HSCT) are at risk for bloodstream infection (BSI) secondary to translocation of bacteria through the injured mucosa, termed mucosal barrier injury-laboratory confirmed bloodstream infection (MBI-LCBI), in addition to BSI secondary to indwelling catheters and infection at other sites (BSI-other). Objective: To determine the incidence, timing, risk factors, and outcomes of patients who develop MBI-LCBI in the first 100 days after HSCT. Design, Setting, and Participants: A case-cohort retrospective analysis was performed using data from the Center for International Blood and Marrow Transplant Research database on 16875 consecutive pediatric and adult patients receiving a first allogeneic HSCT from January 1, 2009, to December 31, 2016. Patients were classified into 4 categories: MBI-LCBI (1481 [8.8%]), MBI-LCBI and BSI-other (698 [4.1%]), BSI-other only (2928 [17.4%]), and controls with no BSI (11768 [69.7%]). Statistical analysis was performed from April 5 to July 17, 2018. Main Outcomes and Measures: Demographic characteristics and outcomes, including overall survival, chronic graft-vs-host disease, and transplant-related mortality (only for patients with malignant disease), were compared among groups. Results: Of the 16875 patients in the study (9737 [57.7%] male; median [range] age, 47 [0.04-82] years) 13686 (81.1%) underwent HSCT for a malignant neoplasm, and 3189 (18.9%) underwent HSCT for a nonmalignant condition. The cumulative incidence of MBI-LCBI was 13% (99% CI, 12%-13%) by day 100, and the cumulative incidence of BSI-other was 21% (99% CI, 21%-22%) by day 100. Median (range) time from transplant to first MBI-LCBI was 8 (<1 to 98) days vs 29 (<1 to 100) days for BSI-other. Multivariable analysis revealed an increased risk of MBI-LCBI with poor Karnofsky/Lansky performance status (hazard ratio [HR], 1.21 [99% CI, 1.04-1.41]), cord blood grafts (HR, 2.89 [99% CI, 1.97-4.24]), myeloablative conditioning (HR, 1.46 [99% CI, 1.19-1.78]), and posttransplant cyclophosphamide graft-vs-host disease prophylaxis (HR, 1.85 [99% CI, 1.38-2.48]). One-year mortality was significantly higher for patients with MBI-LCBI (HR, 1.81 [99% CI, 1.56-2.12]), BSI-other (HR, 1.81 [99% CI, 1.60-2.06]), and MBI-LCBI plus BSI-other (HR, 2.65 [99% CI, 2.17-3.24]) compared with controls. Infection was more commonly reported as a cause of death for patients with MBI-LCBI (139 of 740 [18.8%]), BSI (251 of 1537 [16.3%]), and MBI-LCBI plus BSI (94 of 435 [21.6%]) than for controls (566 of 4740 [11.9%]). Conclusions and Relevance: In this cohort study, MBI-LCBI, in addition to any BSIs, were associated with significant morbidity and mortality after HSCT. Further investigation into risk reduction should be a clinical and scientific priority in this patient population

    An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

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    For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

    Integrating sequence and array data to create an improved 1000 Genomes Project haplotype reference panel

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    A major use of the 1000 Genomes Project (1000GP) data is genotype imputation in genome-wide association studies (GWAS). Here we develop a method to estimate haplotypes from low-coverage sequencing data that can take advantage of single-nucleotide polymorphism (SNP) microarray genotypes on the same samples. First the SNP array data are phased to build a backbone (or 'scaffold') of haplotypes across each chromosome. We then phase the sequence data 'onto' this haplotype scaffold. This approach can take advantage of relatedness between sequenced and non-sequenced samples to improve accuracy. We use this method to create a new 1000GP haplotype reference set for use by the human genetic community. Using a set of validation genotypes at SNP and bi-allelic indels we show that these haplotypes have lower genotype discordance and improved imputation performance into downstream GWAS samples, especially at low-frequency variants. © 2014 Macmillan Publishers Limited. All rights reserved

    Driver Fusions and Their Implications in the Development and Treatment of Human Cancers.

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    Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy
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