Left-sided appendicitis in a patient with congenital gastrointestinal malrotation: a case report

<p>Abstract</p> <p>Background</p> <p>While appendicitis is the most common abdominal disease requiring surgical intervention seen in the emergency room setting, intestinal malrotation is relatively uncommon. When patients with asymptomatic undiagnosed gastrointestinal malrotation clinically present with abdominal pain, accurate diagnosis and definitive therapy may be delayed, possibly increasing the risk of morbidity and mortality. We present a case where CT was crucial diagnostically and helpful for pre-surgical planning in a patient presenting with an acute abdomen superimposed on complete congenital gastrointestinal malrotation.</p> <p>Case presentation</p> <p>A 46-year-old previously healthy male with four days of primarily left-sided abdominal pain, low-grade fevers, nausea and anorexia presented to the Emergency Department. His medical history was significant for poorly controlled diabetes and dyslipidemia. His white blood count at that time was elevated. Initial abdominal plain films suggested small bowel obstruction. A CT scan of the abdomen and pelvis was performed with oral and IV contrast to exclude diverticulitis, revealing acute appendicitis superimposed on congenital intestinal malrotation. Following consultation with the surgical team for surgical planning, the patient went on to laparoscopic appendectomy and did well postoperatively.</p> <p>Conclusion</p> <p>Atypical presentations of acute abdominal conditions superimposed on asymptomatic gastrointestinal malrotation can result in delays in delivery of definitive therapy and potentially increase morbidity and mortality if not diagnosed in a timely manner. Appropriate imaging can be helpful in hastening diagnosis and guiding intervention.</p

Machine learning analysis of complex late gadolinium enhancement patterns to improve risk prediction of major arrhythmic events

Background: Machine learning analysis of complex myocardial scar patterns affords the potential to enhance risk prediction of life-threatening arrhythmia in stable coronary artery disease (CAD). Objective: To assess the utility of computational image analysis, alongside a machine learning (ML) approach, to identify scar microstructure features on late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) that predict major arrhythmic events in patients with CAD. Methods: Patients with stable CAD were prospectively recruited into a CMR registry. Shape-based scar microstructure features characterizing heterogeneous (‘peri-infarct’) and homogeneous (‘core’) fibrosis were extracted. An ensemble of machine learning approaches were used for risk stratification, in addition to conventional analysis using Cox modeling. Results: Of 397 patients (mean LVEF 45.4 ± 16.0) followed for a median of 6 years, 55 patients (14%) experienced a major arrhythmic event. When applied within an ML model for binary classification, peri-infarct zone (PIZ) entropy, peri-infarct components and core interface area outperformed a model representative of the current standard of care (LVEFClass I): AUROC (95%CI) 0.81 (0.81–0.82) vs. 0.64 (0.63–0.65), p = 0.002. In multivariate cox regression analysis, these features again remained significant after adjusting for LVEFClass I: PIZ entropy hazard ratio (HR) 1.88, 95% confidence interval (CI) 1.38–2.56, p < 0.001; number of PIZ components HR 1.34, 95% CI 1.08–1.67, p = 0.009; core interface area HR 1.6, 95% CI 1.29–1.99, p = <0.001. Conclusion: Machine learning models using LGE-CMR scar microstructure improved arrhythmic risk stratification as compared to guideline-based clinical parameters; highlighting a potential novel approach to identifying candidates for implantable cardioverter defibrillators in stable CAD

Living biointerfaces based on non-pathogenic bacteria to direct cell differentiation

Genetically modified Lactococcus lactis, non-pathogenic bacteria expressing the FNIII7-10 fibronectin fragment as a protein membrane have been used to create a living biointerface between synthetic materials and mammalian cells. This FNIII7-10 fragment comprises the RGD and PHSRN sequences of fibronectin to bind α5β1 integrins and triggers signalling for cell adhesion, spreading and differentiation. We used L. lactis strain to colonize material surfaces and produce stable biofilms presenting the FNIII7-10 fragment readily available to cells. Biofilm density is easily tunable and remains stable for several days. Murine C2C12 myoblasts seeded over mature biofilms undergo bipolar alignment and form differentiated myotubes, a process triggered by the FNIII7-10 fragment. This biointerface based on living bacteria can be further modified to express any desired biochemical signal, establishing a new paradigm in biomaterial surface functionalisation for biomedical applications

Management of chronic obstructive pulmonary disease in India: a systematic review.

OBJECTIVES: Chronic diseases are fast becoming the largest health burden in India. Despite this, their management in India has not been well studied. We aimed to systematically review the nature and efficacy of current management strategies for chronic obstructive pulmonary disease (COPD) in India. METHODS: We used database searches (MEDLINE, EMBASE, IndMED, CENTRAL and CINAHL), journal hand-searches, scanning of reference lists and contact with experts to identify studies for systematic review. We did not review management strategies aimed at chronic diseases more generally, nor management of acute exacerbations. Due to the heterogeneity of reviewed studies, meta-analysis was not appropriate. Thus, narrative methods were used. SETTING: India. PARTICIPANTS: All adult populations resident in India. MAIN OUTCOME MEASURES: 1. Trialled interventions and outcomes 2. Extent and efficacy of current management strategies 3. Above outcomes by subgroup. RESULTS: We found information regarding current management - particularly regarding the implementation of national guidelines and primary prevention - to be minimal. This led to difficulty in interpreting studies of management strategies, which were varied and generally of positive effect. Data regarding current management outcomes were very few. CONCLUSIONS: The current understanding of management strategies for COPD in India is limited due to a lack of published data. Determination of the extent of current use of management guidelines, availability and use of treatment, and current primary prevention strategies would be useful. This would also provide evidence on which to interpret existing and future studies of management outcomes and novel interventions

MRI of the lung (3/3)-current applications and future perspectives

BACKGROUND: MRI of the lung is recommended in a number of clinical indications. Having a non-radiation alternative is particularly attractive in children and young subjects, or pregnant women. METHODS: Provided there is sufficient expertise, magnetic resonance imaging (MRI) may be considered as the preferential modality in specific clinical conditions such as cystic fibrosis and acute pulmonary embolism, since additional functional information on respiratory mechanics and regional lung perfusion is provided. In other cases, such as tumours and pneumonia in children, lung MRI may be considered an alternative or adjunct to other modalities with at least similar diagnostic value. RESULTS: In interstitial lung disease, the clinical utility of MRI remains to be proven, but it could provide additional information that will be beneficial in research, or at some stage in clinical practice. Customised protocols for chest imaging combine fast breath-hold acquisitions from a "buffet" of sequences. Having introduced details of imaging protocols in previous articles, the aim of this manuscript is to discuss the advantages and limitations of lung MRI in current clinical practice. CONCLUSION: New developments and future perspectives such as motion-compensated imaging with self-navigated sequences or fast Fourier decomposition MRI for non-contrast enhanced ventilation- and perfusion-weighted imaging of the lung are discussed. Main Messages • MRI evolves as a third lung imaging modality, combining morphological and functional information. • It may be considered first choice in cystic fibrosis and pulmonary embolism of young and pregnant patients. • In other cases (tumours, pneumonia in children), it is an alternative or adjunct to X-ray and CT. • In interstitial lung disease, it serves for research, but the clinical value remains to be proven. • New users are advised to make themselves familiar with the particular advantages and limitations

Pneumonia and in-hospital mortality in the context of neurogenic oropharyngeal dysphagia (NOD) in stroke and a new NOD step-wise concept

The aim of our work was to develop a step-wise concept for investigating neurogenic oropharyngeal dysphagia (NOD) that could be used by both trained nursing staff as well as swallowing therapists and physicians to identify patients with NOD at an early stage and so enable an appropriate therapy to be started. To achieve this objective, we assessed uniform terminology and standard operating procedures (SOP) in a new NOD step-wise concept. In-house stroke mortality rates and rates of pneumonia were measured over time (2003–2009) in order to show improvements in quality of care. In addition, outcome measures in a stroke-unit monitoring system were studied after neurorehabilitation (day 90) assessing quality of life (QL) and patient feedback. An investigation that was carried out in the context of internal and external quality assurance stroke projects revealed a significant correlation between the NOD step-wise concept and low rates of pneumonia and in-house mortality. The quality of life measures show a delta value that can contribute to “post-stroke” depression. The NOD step-wise concept (NSC) should, on the one hand, be capable of being routinely used in clinical care and, on the other, being able to fulfil the requirements of being scientifically based for investigating different stages of swallowing disorders. The value of our NSC relates to the effective management of clinical resources and the provision of adequate diagnostic and therapeutic options for different grades of dysphagia. We anticipate that our concept will provide substantial support to physicians, as well as swallowing therapists, in clinical settings and rehabilitation facilities, thereby promoting better guidance and understanding of neurogenic dysphagia as a concept in acute and rehabilitation care, especially stroke-unit settings

Bicalutamide-induced hypoxia potentiates RUNX2-mediated Bcl-2 expression resulting in apoptosis resistance.

BACKGROUND: We have previously shown that hypoxia selects for more invasive, apoptosis-resistant LNCaP prostate cancer cells, with upregulation of the osteogenic transcription factor RUNX2 and the anti-apoptotic factor Bcl-2 detected in the hypoxia-selected cells. Following this observation, we questioned through what biological mechanism this occurs. METHODS: We examined the effect of hypoxia on RUNX2 expression and the role of RUNX2 in the regulation of Bcl-2 and apoptosis resistance in prostate cancer. RESULTS: Hypoxia increased RUNX2 expression in vitro, and bicalutamide-treated LNCaP tumours in mice (previously shown to have increased tumour hypoxia) exhibited increased RUNX2 expression. In addition, RUNX2-overexpressing LNCaP cells showed increased cell viability, following bicalutamide and docetaxel treatment, which was inhibited by RUNX2 siRNA; a range of assays demonstrated that this was due to resistance to apoptosis. RUNX2 expression was associated with increased Bcl-2 levels, and regulation of Bcl-2 by RUNX2 was confirmed through chromatin immunoprecipitation (ChIP) binding and reporter assays. Moreover, a Q-PCR array identified other apoptosis-associated genes upregulated in the RUNX2-overexpressing LNCaP cells. CONCLUSION: This study establishes a contributing mechanism for progression of prostate cancer cells to a more apoptosis-resistant and thus malignant phenotype, whereby increased expression of RUNX2 modulates the expression of apoptosis-associated factors, specifically Bcl-2

TIEG1/KLF10 Modulates Runx2 Expression and Activity in Osteoblasts

Deletion of TIEG1/KLF10 in mice results in a gender specific osteopenic skeletal phenotype with significant defects in both cortical and trabecular bone, which are observed only in female animals. Calvarial osteoblasts isolated from TIEG1 knockout (KO) mice display reduced expression levels of multiple bone related genes, including Runx2, and exhibit significant delays in their mineralization rates relative to wildtype controls. These data suggest that TIEG1 plays an important role in regulating Runx2 expression in bone and that decreased Runx2 expression in TIEG1 KO mice is in part responsible for the observed osteopenic phenotype. In this manuscript, data is presented demonstrating that over-expression of TIEG1 results in increased expression of Runx2 while repression of TIEG1 results in suppression of Runx2. Transient transfection and chromatin immunoprecipitation assays reveal that TIEG1 directly binds to and activates the Runx2 promoter. The zinc finger containing domain of TIEG1 is necessary for this regulation supporting that activation occurs through direct DNA binding. A role for the ubiquitin/proteasome pathway in fine tuning the regulation of Runx2 expression by TIEG1 is also implicated in this study. Additionally, the regulation of Runx2 expression by cytokines such as TGFβ1 and BMP2 is shown to be inhibited in the absence of TIEG1. Co-immunoprecipitation and co-localization assays indicate that TIEG1 protein associates with Runx2 protein resulting in co-activation of Runx2 transcriptional activity. Lastly, Runx2 adenoviral infection of TIEG1 KO calvarial osteoblasts leads to increased expression of Runx2 and enhancement of their ability to differentiate and mineralize in culture. Taken together, these data implicate an important role for TIEG1 in regulating the expression and activity of Runx2 in osteoblasts and suggest that decreased expression of Runx2 in TIEG1 KO mice contributes to the observed osteopenic bone phenotype

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation