Background. The contribution of methylglyoxal (MGO) and soluble receptor for advanced glycation end products (sRAGE) in the presence of rheumatoid arthritis (RA) is still unknown. We investigated whether serum MGO and sRAGE were related to the presence of disease activity in RA. Methods. 80 patients with RA and 30 control subjects were included in a cross-sectional study. The severity of RA was assessed using the disease activity score for 28 joints (DAS28). Serum MGO and sRAGE were measured by ELISA. Results. Serum MGO levels were significantly higher in patients with RA versus control subjects () and were increased in RA patients with higher disease activity versus RA patients with moderate disease activity (). Serum sRAGE concentrations were significantly decreased in RA patients with higher disease activity versus RA patients with moderate disease activity and versus control subjects (; , resp.). A multiple logistic regression analysis demonstrated that MGO was independently associated with the presence of activity disease in RA (OR = 1.17, 95% CI: 1.02–1.31, ). Conclusion. Serum MGO and sRAGE levels are inversely related to the activity of RA, and MGO is independently associated with a higher disease activity of RA.
http://ift.tt/2H2KLRL
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- Methylglyoxal: A Relevant Marker of Disease Activi...
- Feasibility and accuracy of computer-assisted indi...
- Clinical benefit of improved Prehospital stroke sc...
- The Abnormal Expression of MicroRNA-542-3p in Hepa...
- Rhabdomyosarcoma Revealed by a Breast Metastasis
- Stress Lymphoscintigraphy for Early Detection and ...
- The Value of Regional Cerebral Blood Flow SPECT an...
- Initial Clinical Investigation of [18F]Tetrafluoro...
- Extramedullary Infiltration of Acute Lymphoblastic...
- Relationship Between the Elevated Muscle FDG Uptak...
- 18FDG-PET/CT for the Visualization of Inflammatory...
- Quality and Safety in Health Care, Part XXXIII: Tr...
- Cerebral Abscesses and Osteomyelitis Caused by Fis...
- Amino Acid PET Imaging of the Early Metabolic Resp...
- Primary Spleen Angiosarcoma With Concomitant Hepat...
- Uncomplicated 90Y Selective Internal Radio Therapy...
- Microglial Activation on 11C-CB184 PET in a Patien...
- 18F-NaF PET/CT Finding in a Patient With Abdominal...
- Metastatic Solitary Fibrous Tumor With Doege-Potte...
- Tumor Cystic Necrosis Following Peptide Receptor R...
- Prognostic Value of 99mTc-Sestamibi Parathyroid Sc...
- Orbital Metastasis: Rare Initial Presentation of a...
- Flare on Serial Prostate-Specific Membrane Antigen...
- 18F-FDG PET/CT Detected Delayed Endoleak in an Aor...
- Evaluation and Management of Dehydration in Children
- Pediatric Major Head Injury
- Bronchiolitis
- Emergency Department Management of Pediatric Shock
- Pediatric Emergency Noninvasive Ventilation
- Postoperative Tonsillectomy Hemorrhage
- Pediatric Syncope
- What to Do when Babies Turn Blue
- Pediatric Thoracic Trauma
- Closed-Eye Visualizations in the Setting of Hypona...
- Canada’s evacuation policy for pregnant First Nati...
- Reply to “10-10 Electrode System for EEG Recording”
- Expression of MDM2 and p16 in Angiomyolipoma
- Control of B-1a cell development by instructive BC...
- The regulation of lymphocyte activation and prolif...
- Natural killer cell education in human health and ...
- The ABC of adaptive immunity in liver cancer
- Composition and Properties of Aquafaba: Water Reco...
- Gradient-based optimization with B-splines on spar...
- Intrasplenic Transplantation of Hepatocytes After ...
- Ammonia-oxidizing bacteria and archaea within biof...
- Flow rate dependent continuous hydrolysis of prote...
- NUP98-BPTF gene fusion identified in primary refra...
- FBW7 is associated with prognosis, inhibits malign...
- Mechanisms of CD8+ T cell-mediated suppression of ...
- Nanoparticle-based approaches to immune tolerance ...
- CXCR4-CXCL12 interaction is important for plasma c...
- UBC-Nepal expedition: The use of oral antioxidants...
- Genomic and Physiological Characterization and Des...
- Ice algal bloom development on the surface of the ...
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- From Ruling Out to Ruling In: Putting POCUS in Focus
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- Adaptive design clinical trials: a review of the l...
- Correction: Bluebelle study (phase A): a mixed-met...
- Association between social health insurance and ch...
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- Is socioeconomic segregation of the poor associate...
- Sequelae of multidrug-resistant tuberculosis: prot...
- Risk factors and between-hospital variation of cae...
- Standard echocardiography versus handheld echocard...
- Multicentre study on capsular closure versus non-c...
- Correction: Epidural analgesia in critically ill p...
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- Cryptotanshinone reduces psoriatic epidermal hyper...
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- Multiple roles of SIM2 in esophageal squamous cell...
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Αναζήτηση αυτού του ιστολογίου
Σάββατο 10 Φεβρουαρίου 2018
Methylglyoxal: A Relevant Marker of Disease Activity in Patients with Rheumatoid Arthritis
Feasibility and accuracy of computer-assisted individual drill guide template for minimally invasive lumbar pedicle screw placement trajectory
Publication date: Available online 10 February 2018
Source:Injury
Author(s): Hongwei Wang, Yusheng Liu, Yiwen Zhao, Guoli Song, Jun Liu, Jianda Han, Liangbi Xiang
ObjectiveTo discuss the feasibility and accuracy of a specific computer-assisted individual drill guide template (CIDGT) for minimally invasive lumbar pedicle screw placement trajectory (MI-LPT) through a bovine cadaveric experimental study.DesignA 3-D reconstruction model, including lumbar vertebras (L1–L5), was generated, and the optimal MI-LPTs were determined. A drill guide template with a surface made of the antitemplate of the vertebral surface, including the spinous process and the entry point vertebral surface, was created by reverse engineering and rapid prototyping techniques. Then, MI-LPTs were determined by the drill guide templates, and the trajectories made by K-wires were observed by postoperative CT scan.SettingGeneral Hospital of Shenyang Military Area Command of Chinese PLA.ResultsIn total, 150 K-wires for MI-LPTs were successfully inserted into L1-L5. The required mean time and fluoroscopy times between fixation of the template to the spinous process, entry point vertebral surface, and insertion of the K-wires for minimally invasive lumbar pedicle screw placement trajectories into each vertebra were 79.4 ± 15.0 s and 2.1 ± 0.8 times. There were no significant differences between the preoperative plan and postoperative assessment in the distance from the puncture to the midline and inclination angles according to the different levels (P > 0.05, respectively). The mean deviation between the preoperative plan and postoperative assessment in the distance from the puncture to the midline and inclination angles were 0.8 ± 0.5 mm and 0.9 ± 0.5°, respectively.ConclusionsThe potential use of the novel CIDGT, which was based on the unique morphology of the lumbar vertebra to place minimally invasive lumbar pedicle screws, is promising and could prevent too much radiation exposure intraoperatively.
http://ift.tt/2G3lnd5
Clinical benefit of improved Prehospital stroke scales to detect stroke patients with large vessel occlusions: results from a conditional probabilistic model
Clinical scales to detect large vessel occlusion (LVO) may help to determine the optimal transport destination for patients with suspected acute ischemic stroke (AIS). The clinical benefit associated with impr...
http://ift.tt/2BQ274V
The Abnormal Expression of MicroRNA-542-3p in Hepatocellular Carcinoma and Its Clinical Significance
Aim. To evaluate the expression of miRNA-542-3p in hepatocellular carcinoma, establish its function, and evaluate whether it could serve as a biomarker for diagnosis and prognosis of HCC patients. Methods. qRT-PCR analysis was performed to determine the expression level of miRNA-542-3p in normal liver cells and HCC cell lines. Additionally, samples from TCGA consortium and from our patients were analyzed using biostatistical methods to ascertain whether miR-542-3p could be a good biomarker for HCC diagnosis and prognosis. The effects of miRNA-542-3p on HCC were investigated in HCCLM9 cells. Results. The expression of miRNA-542-3p in HCC cells was significantly downregulated compared with normal liver cells. A lower level of expression of miRNA-542-3p was found in HCC tissue samples than in adjacent normal liver tissue samples from TCGA cases and our patients. Further evaluation revealed that the downregulation was clearly related to aggressive clinicopathological characteristics and affected the prognosis, as low-expressing patients tended to have shorter overall survival. Moreover, cell assays revealed that miR-542-3p overexpression inhibited HCC cell growth and induced apoptosis. Conclusion. We demonstrated for the first time that miRNA-542-3p appears to function as a novel tumor suppressor in HCC and may serve as a promising prognostic biomarker in HCC patients.
http://ift.tt/2Bl2hQO
Rhabdomyosarcoma Revealed by a Breast Metastasis
http://ift.tt/2BTAsQo
Stress Lymphoscintigraphy for Early Detection and Management of Secondary Limb Lymphedema
http://ift.tt/2Bl1BLg
The Value of Regional Cerebral Blood Flow SPECT and FDG PET in Operculoinsular Epilepsy
http://ift.tt/2BOGBh3
Initial Clinical Investigation of [18F]Tetrafluoroborate PET/CT in Comparison to [124I]Iodine PET/CT for Imaging Thyroid Cancer
http://ift.tt/2BoI0tI
Extramedullary Infiltration of Acute Lymphoblastic Leukemia in Multiple Organs on FDG PET/CT
http://ift.tt/2BSuNdB
Relationship Between the Elevated Muscle FDG Uptake in the Distal Upper Extremities on PET/CT Scan and Prescan Utilization of Mobile Devices in Young Patients
http://ift.tt/2BlMYXT
18FDG-PET/CT for the Visualization of Inflammatory Component of Radiation-Induced Lung Injury After Stereotactic Radiotherapy
http://ift.tt/2BRDOUe
Quality and Safety in Health Care, Part XXXIII: Transcatheter Mitral Valve Therapy
http://ift.tt/2Bn9q31
Cerebral Abscesses and Osteomyelitis Caused by Fish Bone Impaction on FDG PET/CT Imaging
http://ift.tt/2BSl9I3
Amino Acid PET Imaging of the Early Metabolic Response During Tumor-Treating Fields (TTFields) Therapy in Recurrent Glioblastoma
http://ift.tt/2BkByUe
Primary Spleen Angiosarcoma With Concomitant Hepatic Hemangiomas on 18F-FDG PET/CT
http://ift.tt/2BRjfHg
Uncomplicated 90Y Selective Internal Radio Therapy in a Patient With Hepatocellular Carcinoma After Arterial and Portal Vein Embolizations
http://ift.tt/2BnQGAx
Microglial Activation on 11C-CB184 PET in a Patient With Cerebellar Ataxia Associated With HIV Infection
http://ift.tt/2BS6VXC
18F-NaF PET/CT Finding in a Patient With Abdominal Discomfort After Schistosomiasis
http://ift.tt/2BkBxQa
Metastatic Solitary Fibrous Tumor With Doege-Potter Syndrome: Hypoglycemia Treated by 90Y Radioembolization
http://ift.tt/2BQILwq
Tumor Cystic Necrosis Following Peptide Receptor Radionuclide Therapy in Neuroendocrine Tumors
http://ift.tt/2Bmcexg
Prognostic Value of 99mTc-Sestamibi Parathyroid Scintigraphy in Predicting Future Surgical Eligibility in Patients With Asymptomatic Primary Hyperparathyroidism
http://ift.tt/2BOGB0x
Orbital Metastasis: Rare Initial Presentation of an Occult Gall Bladder Carcinoma
http://ift.tt/2Bm3Uxv
Flare on Serial Prostate-Specific Membrane Antigen–Targeted 18F-DCFPyL PET/CT Examinations in Castration-Resistant Prostate Cancer: First Observations
http://ift.tt/2BSl72T
18F-FDG PET/CT Detected Delayed Endoleak in an Aortoiliac Endovascular Aneurysm Repair
http://ift.tt/2BkBwf4
Evaluation and Management of Dehydration in Children
The article discusses the evaluation of dehydration in children and reviews the literature on physical findings of dehydration. Pediatric dehydration is a common problem in emergency departments and wide practice variation in treatment exists. Dehydration can be treated with oral, nasogastric, subcutaneous, or intravenous fluids. Although oral rehydration is underutilized in the United States, most children with dehydration can be successfully rehydrated via the oral route. Selection of oral rehydration solution and techniques for successful oral rehydration are presented. Appropriate selection and rate of administration of intravenous fluids are also discussed for isonatremic, hyponatremic, and hypernatremic dehydration.
http://ift.tt/2BoGNTc
Pediatric Major Head Injury
Traumatic brain injury is a highly prevalent and devastating cause of morbidity and mortality in children. A rapid, stepwise approach to the traumatized child should proceed, addressing life-threatening problems first. Management focuses on preventing secondary injury from physiologic extremes such as hypoxemia, hypotension, prolonged hyperventilation, temperature extremes, and rapid changes in cerebral blood flow. Initial Glasgow Coma Score, hyperglycemia, and imaging are often prognostic of outcome. Surgically amenable lesions should be evacuated promptly. Reduction of intracranial pressure through hyperosmolar therapy, decompressive craniotomy, and seizure prophylaxis may be considered after stabilization. Nonaccidental trauma should be considered when evaluating pediatric trauma patients.
http://ift.tt/2BQYlrQ
Bronchiolitis
The American Academy of Pediatrics' clinical practice guideline in bronchiolitis was last updated in 2014 with recommendations to improve care for pediatric patients with bronchiolitis. As most treatments of bronchiolitis are supportive, the guideline minimizes the breadth of treatments previously used and cautions the use of tests and therapies that have a limited evidence base. Emergency physicians must be familiar with the guidelines in order to apply best practices appropriately.
http://ift.tt/2BoGI1Q
Emergency Department Management of Pediatric Shock
Shock, a state of inadequate oxygen delivery to tissues resulting in anaerobic metabolism, lactate accumulation, and end-organ dysfunction, is common in children in emergency department. Shock can be divided into 4 categories: hypovolemic, distributive, cardiogenic, and obstructive. Early recognition of shock can be made with close attention to historical clues, physical examination and vital sign abnormalities. Early and aggressive treatment can prevent or reverse organ dysfunction and improve morbidity and mortality.
http://ift.tt/2BSHncL
Pediatric Emergency Noninvasive Ventilation
Noninvasive ventilation (NIV) has emerged as a powerful tool for the pediatric emergency management of acute respiratory failure (ARF). This therapy is safe and well tolerated and seems to frequently prevent both the need for invasive mechanical ventilation and the associated risks/complications. Although NIV can be the primary treatment of ARF resulting from multiple respiratory disease states, it must be meticulously monitored and, when unsuccessful, may aid in preoxygenation for prompt endotracheal intubation and invasive mechanical ventilation. The following article reviews the physiologic effects of NIV and its role in common respiratory diseases encountered in pediatric emergency medicine.
http://ift.tt/2BmarZ4
Postoperative Tonsillectomy Hemorrhage
Post-tonsillectomy hemorrhage represents a potentially life-threatening condition that occurs in up to 5% of pediatric patients. Minor bleeding often precedes severe hemorrhage. Patients with minor or self-resolving bleeding should be observed in the emergency department or admitted for monitoring. Patients with severe bleeding should be immediately assessed for airway and hemodynamic stability. Management of severe bleeding includes immediate surgical consultation or initiation of the transfer process to a center with surgical capabilities, direct pressure to the site of hemorrhage with or without the additional of a hemostatic agent, possible rapid sequence intubation, and management of hemodynamic instability with volume resuscitation.
http://ift.tt/2BQMNVM
Pediatric Syncope
Syncope is a common presentation to the emergency room. Unlike in the adult population, most pediatric syncope has non-life-threatening causes, and minimal evaluation in the emergency department is appropriate with parental reassurance. Despite this benign prognosis, care must be made to find uncommon and potentially fatal causes. The primary purpose of evaluation of the patient with syncope is to determine whether the patient is at increased risk for death and needs either admission to the hospital or an expedited outpatient evaluation. This article reviews some of the most dangerous causes of syncope in the pediatric patient.
http://ift.tt/2BnPnBh
What to Do when Babies Turn Blue
The term "brief resolved unexplained event" was created to replace "apparent life-threatening event," narrowing the definition and providing evidence-based guidelines for management. The emphasis is placed on using clinical clues to classify patients as low risk or exclude them from the categorization altogether. Infants who meet low-risk classification can be briefly observed in the emergency department and be discharged home. Infants who demonstrate elements suggestive of a specific etiology should be evaluated and treated accordingly. Patients who demonstrate no specific findings yet who are high risk should be evaluated for the most common etiologies of apneic events and be admitted.
http://ift.tt/2BQaDRx
Pediatric Thoracic Trauma
Thoracic injuries account for less than one-tenth of all pediatric trauma-related injuries but comprise 14% of pediatric trauma-related deaths. Thoracic trauma includes injuries to the lungs, heart, aorta and great vessels, esophagus, tracheobronchial tree, and structures of the chest wall. Children have unique anatomic features that change the patterns of observed injury compared with adults. This review article outlines the clinical presentation, diagnostic testing, and management principles required to successfully manage injured children with thoracic trauma.
http://ift.tt/2BoGpEe
Closed-Eye Visualizations in the Setting of Hyponatremia
Purpose. To report a case of closed-eye visualizations and to clarify the different types of hallucinations and their etiologies. Methods. Retrospective case report of a patient with closed-eye visualizations secondary to hyponatremia. Clinical findings, physical exam, laboratory assessment, treatment, and disease course from the patient's hospitalization were used in creating this report. Follow-up data after discharge were also obtained. Results. Closed-eye visualizations were diagnosed as secondary to hyponatremia, as they did not occur with the eyes open, and potential alternate causes were excluded. Serum sodium nadir was 119 mEq/L. Symptoms resolved with correction of hyponatremia via fluid resuscitation and electrolyte replenishment. There has been no recurrence of the symptoms. Conclusion. This patient had hallucinations exclusively with the eyes closed, which must be differentiated from the release hallucinations seen with the eyes open in Charles Bonnet syndrome. This patient had no visual loss or retinal disease, which should be suspected in open eye hallucinations.
http://ift.tt/2Ca4ivT
Canada’s evacuation policy for pregnant First Nations women: Resignation, resilience, and resistance
Publication date: Available online 10 February 2018
Source:Women and Birth
Author(s): Karen M. Lawford, Audrey R. Giles, Ivy L. Bourgeault
BackgroundAboriginal peoples in Canada are comprised of First Nations, Métis, and Inuit. Health care services for First Nations who live on rural and remote reserves are mostly provided by the Government of Canada through the federal department, Health Canada. One Health Canada policy, the evacuation policy, requires all First Nations women living on rural and remote reserves to leave their communities between 36 and 38 weeks gestational age and travel to urban centres to await labour and birth. Although there are a few First Nations communities in Canada that have re-established community birthing and Aboriginal midwifery is growing, most First Nations communities are still reliant on the evacuation policy for labour and birthing services. In one Canadian province, Manitoba, First Nations women are evacuated to The Pas, Thompson, or Winnipeg but most – including all women with high-risk pregnancies – go to Winnipeg.AimTo contribute scholarship that describes First Nations women's and community members' experiences and perspectives of Health Canada's evacuation policy in Manitoba.MethodsApplying intersectional theory to data collected through 12 semi-structured interviews with seven women and five community members (four females, one male) in Manitoba who had experienced the evacuation policy. The data were analyzed thematically, which revealed three themes: resignation, resilience, and resistance.FindingsThe theme of resignation was epitomized by the quote, "Nobody has a choice." The ability to withstand and endure the evacuation policy despite poor or absent communication and loneliness informed of resilience. Resistance was demonstrated by women who questioned the necessity and requirement of evacuation for labour and birth. In one instance, resistance took the form of a planned homebirth with Aboriginal registered midwives.ConclusionThere is a pressing need to improve the maternity care services that First Nations women receive when they are evacuated out of their communities, particularly when understood from the specific legal and constitutional position of First Nations women in Manitoba.
http://ift.tt/2EgZaIe
Reply to “10-10 Electrode System for EEG Recording”
We thank Prof. Nuwer for providing additional information on the 10-10-system (Nuwer, 2018) which helps to put the development of the current EEG-nomenclature and related discussions in the correct historical context to which Prof Nuwer contributed significantly. We, as the international clinical neurophysiological community, continue to try to improve not only the nomenclature, but our clinical tools and their implementation to improve the patient care – which would have not been possible without the commitment of colleagues active in the field like Prof Nuwer.
http://ift.tt/2nR6e8j
Expression of MDM2 and p16 in Angiomyolipoma
Angiomyolipoma (AML) arises primarily from the kidney, but may grow into the retroperitoneal space mimicking a primary retroperitoneal tumor. Fine needle aspiration (FNA) and core needle biopsy (CNB) of AML, particularly the fat-predominant variant, may be difficult to distinguish from retroperitoneal well-differentiated liposarcoma (WDLS) or lipoma. Commonly used immunomarkers, MDM2 and p16, have proven useful in diagnosing WDLS and dedifferentiated liposarcoma (DDLS), while HMB45 and Melan-A are melanocyte-related markers characteristically expressed in AML.
http://ift.tt/2EvIu2R
Control of B-1a cell development by instructive BCR signaling
Taras Kreslavsky | Jason B Wong | Maria Fischer | Jane A Skok | Meinrad Busslinger
http://ift.tt/2EyVvsD
The regulation of lymphocyte activation and proliferation
Susanne Heinzel | Julia M Marchingo | Miles B Horton | Philip D Hodgkin
http://ift.tt/2EwD2g4
Natural killer cell education in human health and disease
Jeanette E Boudreau | Katharine C Hsu
http://ift.tt/2G3hzsD
Composition and Properties of Aquafaba: Water Recovered from Commercially Canned Chickpeas
http://ift.tt/2ERba45
Gradient-based optimization with B-splines on sparse grids for solving forward-dynamics simulations of three-dimensional, continuum-mechanical musculoskeletal system models
Abstract
Investigating the interplay between muscular activity and motion is the basis to improve our understanding of healthy or diseased musculoskeletal systems. To be able to analyze the musculoskeletal systems, computational models are employed. Albeit some severe modeling assumptions, almost all existing musculoskeletal system simulations appeal to multi-body simulation frameworks. Although continuum-mechanical musculoskeletal system models can compensate for some of these limitations, they are essentially not considered due to their computational complexity and cost. The proposed framework is the first activation-driven musculoskeletal system model, in which the exerted skeletal muscle forces are computed using three-dimensional, continuum-mechanical skeletal muscle models and in which muscle activations are determined based on a constraint optimization problem. Numerical feasibility is achieved by computing sparse grid surrogates with hierarchical B-splines, and adaptive sparse grid refinement further reduces the computational effort. The choice of B-splines allows the use of all existing gradient-based optimization techniques without further numerical approximation. This paper demonstrates that the resulting surrogates have low relative errors (less than 0.76%) and can be used within forward simulations that are subject to constraint optimization. To demonstrate this, we set up several different test scenarios in which an upper limb model consisting of the elbow joint, the biceps and triceps brachii and an external load is subjected to different optimization criteria. Even though this novel method has only been demonstrated for a two-muscle system, it can easily be extended to musculoskeletal systems with three or more muscles. This article is protected by copyright. All rights reserved.
http://ift.tt/2Ev8XxE
Intrasplenic Transplantation of Hepatocytes After Partial Hepatectomy in NOD.SCID Mice
http://ift.tt/2H6VP0g
Ammonia-oxidizing bacteria and archaea within biofilters of a commercial recirculating marine aquaculture system
While biofilters are widely used to metabolize ammonia and other wastes in marine recirculating aquaculture systems, the ammonia-oxidizing bacterial and archaeal communities have not been characterized across ...
http://ift.tt/2nSwwqF
Flow rate dependent continuous hydrolysis of protein isolates
Food protein hydrolysates are often produced in unspecific industrial batch processes. The hydrolysates composition underlies process-related fluctuations and therefore the obtained peptide fingerprint and bio...
http://ift.tt/2nWUikl
NUP98-BPTF gene fusion identified in primary refractory acute megakaryoblastic leukemia of infancy
Abstract
The advent of large scale genomic sequencing technologies significantly improved the molecular classification of acute megakaryoblastic leukaemia (AMKL). AMKL represents a subset (∼10%) of high fatality pediatric acute myeloid leukemia (AML). Recurrent and mutually exclusive chimeric gene fusions associated with pediatric AMKL are found in 60-70% of cases and include RBM15-MKL1, CBFA2T3-GLIS2, NUP98-KDM5A and MLL rearrangements. In addition, another 4% of AMKL harbor NUP98 rearrangements (NUP98r), with yet undetermined fusion partners. We report a novel NUP98-BPTF fusion in an infant presenting with primary refractory AMKL. In this NUP98r, the C-terminal chromatin recognition modules of BPTF, a core subunit of the NURF (Nucleosome Remodeling Factor) ATP-dependent chromatin-remodeling complex, are fused to the N-terminal moiety of NUP98, creating and in frame NUP98-BPTF fusion, with structural homology to NUP98-KDM5A. The leukemic blasts expressed two NUP98-BPTF splicing variants, containing one or two tandemly spaced PHD chromatin reader domains. Our study also identified an unreported wild type BPTF splicing variant encoding for 2 PHD domains, detected both in normal cord blood CD34+ cells and in leukemic blasts, as with the fly BPTF homolog, Nurf301. Disease course was marked by rapid progression and primary chemoresistance, with ultimately significant tumor burden reduction following treatment with a clofarabine containing regimen. In sum, we report 2 novel NUP98-BPTF fusion isoforms that contribute to refine the NUP98r subgroup of pediatric AMKL. Multicenter clinical trials are critically required to determine the frequency of this fusion in AMKL patients and explore innovative treatment strategies for a disease still plagued with poor outcomes. This article is protected by copyright. All rights reserved.
http://ift.tt/2BlZNBw
FBW7 is associated with prognosis, inhibits malignancies and enhances temozolomide sensitivity in glioblastoma cells
Abstract
F-box and WD repeat domain-containing 7(FBW7) is a SCF-type E3 ubiquitin ligase targeting a multitude of oncoproteins for degradation. Acting as one of the most important tumor suppressor it is frequently inactivated in various tumors. In this study we aimed to evaluate the relationship of FBW7 with glioma pathology and prognosis, and examine its effect in glioma malignancies and temozolomide(TMZ)-based therapy. Clinical tissues and TCGA database analysis revealed FBW7 expression was correlated inversely with glioma histology and positively with patient survival time. Lentivirus transfection- induced FBW7 overexpression significantly suppressed proliferation, invasion and migration of U251 and U373 cells whereas knockdown of FBW7 by targeted shRNA promoted proliferation, invasion and migration of glioma cells. Most importantly, the expression level of FBW7 was found to affect 50% inhibition concentration(IC50) of U251 and the TMZ resistant variant. Combining TMZ with FBW7 overexpression notably increased the cytotoxicity than TMZ treatment alone, which was conversely attenuated by FBW7 knockdown. Moreover, flow cytometry(FC) analysis showed either overexpression of FBW7, TMZ or the combination increased proportion of G2/M arrest and apoptotic rate whereas FBW7 inhibition reduced G2/M arrest and apoptosis in U251 cells. Finally, mechanistic study found FBW7 overexpression downregulated Aurora B, Mcl1 and Notch1 levels in a time-dependent pattern and this expressional suppression was independent of TMZ. These findings collectively demonstrate the critical role of FBW7 as a prognostic factor and a potential target to overcome chemoresistance of glioblastoma.
This article is protected by copyright. All rights reserved.
http://ift.tt/2ET4ZN5
Mechanisms of CD8+ T cell-mediated suppression of HIV/SIV replication
Abstract
In this article, we summarize the role of CD8+ T cells during natural and ART-treated HIV and SIV infections, discuss the mechanisms responsible for their suppressive activity, and review the rationale for CD8+ T cell-based HIV cure strategies. Evidence suggests that CD8+ T cells are involved in the control of virus replication during HIV and SIV infections. During early HIV infection, the cytolytic activity of CD8+ T cells is responsible for control of viremia. However, it has been proposed that CD8+ T cells also use non-cytolytic mechanisms to control SIV infection. More recently, CD8+ T cells were shown to be required to fully suppress virus production in ART-treated SIV-infected macaques, suggesting that CD8+ T cells are involved in the control of virus transcription in latently infected cells that persist under ART. A better understanding of the complex antiviral activities of CD8+ T cells during HIV/SIV infection will pave the way for immune interventions aimed at harnessing these functions to target the HIV reservoir.
This article is protected by copyright. All rights reserved
http://ift.tt/2EUp5qg
Nanoparticle-based approaches to immune tolerance for the treatment of autoimmune diseases
Abstract
Autoimmune diseases are caused by antigenically complex immune responses of the adaptive and innate immune system against specific cells, tissues or organs. Antigen-specific approaches for induction of immune tolerance in autoimmunity, based on the use of antigenic peptides or proteins, have failed to deliver the desired therapeutic results in clinical trials. These approaches, which are largely relying on triggering clonal anergy and/or deletion of defined autoreactive specificities, do not address the overwhelming antigenic, molecular and cellular complexity of most autoimmune diseases, which involve various immune cells and ever-growing repertoires of antigenic epitopes on numerous self-antigens. Advances in the field of regulatory T-cell (Treg) biology have suggested that Treg cells might be able to afford dominant tolerance provided they are properly activated and expanded in vivo. More recently, nanotechnology has introduced novel technical advances capable of modulating immune responses. Here, we review nanoparticle-based approaches designed to induce immune tolerance, ranging from approaches that primarily trigger clonal T-cell anergy or deletion, to approaches that trigger Treg cell formation and expansion from autoreactive T-cell effectors. We will also highlight the therapeutic potential and positive outcomes in numerous experimental models of autoimmunity.
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CXCR4-CXCL12 interaction is important for plasma cell homing and survival in NZB/W mice
Abstract
Antibody-secreting cells (ASCs), including short-lived plasmablasts and long-lived memory plasma cells (LLPCs), contribute to autoimmune pathology. ASCs, particularly LLPCs, refractory to conventional immunosuppressive drugs pose a major therapeutic challenge. Since stromal cells expressing C-X-C motif chemokine-12 (CXCL12) organize survival niches for LLPCs in the bone marrow, we investigated the effects of CXCL12 and its ligand CXCR4 on ASCs in lupus mice (NZB/W). Fewer adoptively transferred splenic ASCs were retrieved from the bone marrow of recipient immunodeficient Rag1−/− mice when the ASCs were pre-treated with the CXCR4 blocker AMD3100. CXCR4 blockade also significantly reduced anti-OVA ASCs in the bone marrow after secondary immunization with ovalbumin (OVA). In this study, AMD3100 efficiently depleted ASCs, including LLPCs. After two weeks, it decreased the total number of ASCs in the spleen and bone marrow by more than 60%. Combination with the proteasome inhibitor bortezomib significantly enhanced the depletion effect of AMD3100. Continuous long-term (five-month) CXCR4 blockade with AMD3100 after effective short-term LLPCs depletion kept the number of LLPCs in the bone marrow low, delayed proteinuria development and prolonged the survival of the mice. These findings identify the CXCR4-CXCL12 axis as a potential therapeutic target likely due to its importance for ASC homing and survival.
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UBC-Nepal expedition: The use of oral antioxidants does not alter cerebrovascular function at sea-level or high-altitude
Abstract
Hypoxia is associated with an increased systemic and cerebral formation of free radicals and associated reactants that may be linked to impaired cerebral vascular function a neurological sequela. To what extent oral antioxidants prophylaxis impacts cerebrovascular function in humans throughout the course of acclimatization to the hypoxia of terrestrial high-altitude has not been examined. Thus, the purpose of the current study was to examine the influence of orally ingested antioxidants at clinically relevant doses (vitamin C, E, and alpha-lipoic acid) on cerebrovascular regulation at sea-level (344 m; n = 12; female n = 2 participants), and at high altitude (5050 m; n = 9; female n = 2), in a randomized, placebo-controlled, and double-blinded crossover design. Hypercapnic and hypoxic cerebrovascular reactivity tests of the internal carotid (ICA)] were conducted at sea-level, while global and regional cerebral blood flow [i.e. ICA and vertebral artery (VA)] were assessed after 10–12 days following arrival at 5050 m. At sea-level, acute administration of antioxidants did not alter cerebral hypoxic cerebrovascular reactivity (pre vs. post: 1.5 ± 0.7 vs. 1.2 ± 0.8 %∆CBF/-%∆SpO2; P = 0.96), or cerebral hypercapnic cerebrovascular reactivity (pre vs. post: 5.7 ± 2.0 vs. 5.8 ± 1.9 %∆CBF/∆mmHg; P = 0.33). Furthermore, global cerebral blood flow (P = 0.43), as well as cerebral vascular conductance (ICA P = 0.08; VA P = 0.32), were unaltered at 5050 m following antioxidant administration. In conclusion, these data show that an oral antioxidant cocktail known to attenuate systemic oxidative stress failed to alter cerebrovascular function at sea-level and cerebral blood flow during acclimatization to high-altitude.
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Genomic and Physiological Characterization and Description of Marinobacter gelidimuriae sp. nov., a Psychrophilic, Moderate Halophile From Blood Falls, an Antarctic Subglacial Brine
http://ift.tt/2sqeCAq
Ice algal bloom development on the surface of the Greenland Ice Sheet
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The expression and function of galectins in skin physiology and pathology
Abstract
The galectin family comprises β-galactoside-binding proteins widely expressed in many organisms. There are at least 16 family members, which can be classified into three groups based on their carbohydrate-recognition domains. Pleiotropic functions of different galectins in physiological and pathological processes through extracellular or intracellular actions have been revealed. In the skin, galectins are expressed in a variety of cells, including keratinocytes, melanocytes, fibroblasts, dendritic cells, lymphocytes, macrophages, and endothelial cells. Expression of specific galectins is reported to affect cell status, such as activation or death, and regulate the interaction between different cell types or between cells and the extracellular matrix. In vitro cellular studies, in vivo animal studies and studies of human clinical material have revealed the pathophysiologic roles of galectins in the skin. The pathogenesis of diverse non-malignant skin disorders, such as atopic dermatitis, psoriasis, contact dermatitis, and wound healing, as well as skin cancers, such as melanoma, squamous cell carcinoma, basal cell carcinoma, and cutaneous hematologic malignancy can be regulated by different galectins. Revelation of biological roles of galectins in skin may pave the way to future development of galectin-based therapeutic strategies for skin diseases.
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The accuracy and prognostic value of point-of-care ultrasound for nephrolithiasis in the emergency department: A Systematic Review and Meta-Analysis
Abstract
Introduction
Point-of-care ultrasound (POCUS) has been suggested as an initial investigation in the management of renal colic. Our objectives were: 1) to determine the accuracy of POCUS for the diagnosis of nephrolithiasis, and 2) to assess its prognostic value in the management of renal colic.
Methods
The review protocol was registered to the PROSPERO database (CRD42016035331). An electronic database search of MEDLINE, EMBASE, and PubMed was conducted utilizing subject headings, keywords, and synonyms that address our research question. Bibliographies of included studies and narrative reviews were manually examined. Studies of adult emergency department patients with renal colic symptoms were included. Any degree of hydronephrosis was considered a positive POCUS finding. Accepted criterion standards were CT evidence of renal stone or hydronephrosis, direct stone visualization, or surgical findings. Screening of abstracts, quality assessment with the QUADAS-2 instrument, and data extraction were performed by two reviewers, with discrepancies resolved by consensus with a third reviewer.
Test performance was assessed by pooled sensitivity and specificity, calculated likelihood ratios, and a summary receiver operator curve (SROC). The secondary objective of prognostic value was reported as a narrative summary.
Results
The electronic search yielded 627 unique titles. After relevance screening, 26 papers underwent full-text review, and 9 articles met all inclusion criteria. Of these, 5 high-quality studies (N = 1773) were included in the meta-analysis for diagnostic accuracy, and the remaining yielded data on prognostic value. The pooled results for sensitivity and specificity were 70.2% (95% CI = 67.1% to 73.2%) and 75.4% (95% CI = 72.5% to 78.2%), respectively. The calculated positive and negative likelihood ratios were 2.85 and 0.39. The SROC generated did not show evidence of a threshold effect. Two of the studies in the meta-analysis found that the finding of moderate or greater hydronephrosis yielded a specificity of 94.4% (95% CI = 92.7% to 95.8%).
Four studies examining prognostic value noted a higher likelihood of a large stone when positive POCUS findings were present. The largest randomized trial showed lower cumulative radiation exposure and no increase in adverse events in those who received POCUS investigation as the initial renal colic investigation.
Conclusion
Point-of-care ultrasound has modest diagnostic accuracy for diagnosing nephrolithiasis. The finding of moderate or severe hydronephrosis is highly specific for the presence of any stone, and the presence of any hydronephrosis is suggestive of a larger (>5mm) stone in those presenting with renal colic.
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From Ruling Out to Ruling In: Putting POCUS in Focus
Abstract
Over the past twenty years, the Emergency Department (ED) has transformed from a location that managed patients with acute life-threatening illness or injury to an acute diagnostic center. The advent of rapid and accurate imaging, novel biomarkers, and other innovations concurrent with effects from financial and social forces has supported the development of an acute care system focused on "ruling out" low-frequency, high-mortality events such as acute myocardial infarction, stroke, pulmonary embolism, and aortic dissection. This search for "true-negatives" may result from malpractice fears, readily available technology, or most likely, clinician and patient discomfort with uncertainty. As a result, diagnostic testing is ubiquitous and costs of care continue to rise. A notable example of this trend has been the rapid increase in computed tomography (CT) utilization for patients with renal colic despite little evidence of major improvements in outcomes.
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Economic Analysis of Diagnostic Imaging in Pediatric Patients with Suspected Appendicitis
Abstract
Objective
The use of computed tomography (CT) and ultrasound (US) in patients with acute abdominal pain has substantial variation across pediatric emergency departments (ED). This study compares the cost of diagnosing and treating suspected appendicitis across a multi-center network of children's hospitals.
Methods
This study is a secondary analysis using de-identified data of a prospective, observational study of patients with suspected appendicitis at nine pediatric EDs. The study included patients 3-18 years old who presented to the ED with acute abdominal pain of < 96 hours duration.
Results
Our data-set contained 2300 cases across nine sites. There was an appendicitis rate of 31.8% and perforation rate of 25.7%. Sites correctly diagnosed appendicitis in over 95% of cases. The negative appendicitis rate ranged from 2.5% to 4.7% while the missed appendicitis rate ranged from 0.3% to 1.1% with no significant differences in these rates across site. Across sites, we found a strong positive correlation (0.95) between CT rate and total cost per case and a strong negative correlation (-0.71) between US rate and cost. The cost per case at US sites was 5.2% ($367) less than at CT sites (p<0.001). Similarly, cost per case at mixed sites were 3.4% ($244) less than at CT sites (p<0.001). Comparing costs among CT sites or among US sites, the cost per case generally increased as the images per case increased among both CT sites and US sites, but the costs were universally higher at CT sites.
Conclusions
Our results provide support for US as the primary imaging modality for appendicitis. Sites that preferentially utilized US had lower costs per case than sites that primarily used CT. Imaging rates across sites varied due to practice patterns and resulted in a significant cost consequence without higher rates for negative appendectomies or missed appendicitis cases.
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Prospective validation and refinement of a decision rule to obtain CXR in patients with non-traumatic chest pain in the ED
Abstract
Objectives
To prospectively validate and refine previously published criteria to determine the potential utility of chest x-ray (CXR) in the evaluation and management of patients presenting to the emergency department (ED) with non-traumatic chest pain.
Methods
A prospective observational study was performed of patients presenting to three EDs in the US with a chief complaint of non-traumatic chest pain. Previously defined high-risk history and exam elements were combined into a refined decision rule and these elements were recorded for each patient by the ED physician. CXR results were reviewed and analyzed to determine the presence of clinically significant findings including pneumonia, pleural effusion, pneumothorax, congestive heart failure, or the presence of a new mass. Odds ratios for each history and exam element were analyzed as well as sensitivity, specificity, and negative predictive value of the rule overall.
Results
1111 patients were enrolled and 1089 CXRs were analyzed. There were 70 (6.4%) patients with clinically relevant findings on CXR. The refined decision rule had a sensitivity of 92.9% (CI 83.4%-97.3%) and specificity of 30.4% (CI 27.6%-33.4%) to predict clinically relevant findings on CXR, with a negative predictive value of 98.4% (CI 96.1%-99.4%). Five CXRs with clinically significant findings would have been missed by application of the refined rule (3 pneumonias and 2 pleural effusions). Applying these criteria as a CXR decision rule to this population would have reduced CXR utilization by 28.9%.
Conclusions
This study validates previous research suggesting a low clinical yield for CXR in the setting of non-traumatic chest pain in the ED. This refined clinical decision rule has a favorable sensitivity and negative predictive value in a patient population with low incidence of disease. Further validation is needed prior to use in practice.
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Malignant rhabdoid tumors originating within and outside the central nervous system are clinically and molecularly heterogeneous
Abstract
Multifocal synchronous or metachronous atypical teratoid rhabdoid tumors (ATRTs) and non-central nervous system malignant rhabdoid tumors (extra-CNS MRTs) are rare cancers. We reviewed the clinical and radiologic characteristics of affected patients seen at our institution. Genotyping and analysis of copy number abnormalities (CNAs) in SMARCB1 were performed in germline and tumor samples. Tumor samples underwent genome-wide DNA methylation and CNA analysis. The median age at diagnosis of 21 patients was 0.6 years. Two-thirds of ATRTs and extra-CNS MRTs were diagnosed synchronously. Although kidney tumors predominated, including two patients with bilateral involvement, at least 30% of cases lacked renal involvement. Histopathologic review confirmed MRTs in all cases and INI1 expression loss in all tumors tested. Fourteen (78%) of 18 patients tested had heterozygous germline SMARCB1 abnormalities. At least one allelic SMARCB1 abnormality was confirmed in 81 and 88% of ATRTs and extra-CNS MRTs, respectively. Unsupervised hierarchical clustering analysis of DNA methylation in 27 tumors and comparison with a reference group of 150 ATRTs classified the CNS tumors (n = 14) as sonic hedgehog (64%), tyrosinase (21%), and MYC (14%). The MYC subgroup accounted for 85% of 13 extra-CNS MRTs. Of 16 paired ATRTs and extra-CNS MRTs, the tumors in seven of eight patients showed a different pattern of genome-wide DNA methylation and/or CNAs suggestive of non-clonal origin. CNS and extra-CNS tumors had an identical SMARCB1 amplification (n = 1) or very similar DNA methylation pattern (n = 1) suggestive of clonal origin. All patients died of tumor progression. The clinical and molecular characteristics of multifocal ATRTs and extra-CNS MRTs are heterogeneous with most patients harboring a cancer predisposition. Although independent tumor origin was confirmed in most cases, metastatic spread was also documented. The recognition of their distinct molecular characteristics is critical in selecting new biologic therapies against these deadly cancers.
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5-Hydroxymethylcytosine preferentially targets genes upregulated in isocitrate dehydrogenase 1 mutant high-grade glioma
Abstract
Gliomas demonstrate epigenetic dysregulation exemplified by the Glioma CpG Island Methylator Phenotype (G-CIMP) seen in IDH1 mutant tumors. 5-Hydroxymethylcytosine (5hmC) is implicated in glioma pathogenesis; however, its role in IDH1 mutant gliomas is incompletely understood. To characterize 5hmC in IDH1 mutant gliomas further, we examine 5hmC in a cohort of IDH1 mutant and wild-type high-grade gliomas (HGG) using a quantitative locus-specific approach. Regions demonstrating high 5hmC abundance and differentially hydroxymethylated regions (DHMR) enrich for enhancers implicated in glioma pathogenesis. Among these regions, IDH1 mutant tumors possess greater 5hmC compared to wild type. 5hmC contributes to overall methylation status of G-CIMP genes. 5hmC targeting gene body regions correlates significantly with increased gene expression. In particular, a strong correlation between increased 5hmC and increased gene expression is identified for genes highly expressed in the IDH1 mutant cohort. Overall, locus-specific gain of 5hmC targeting regulatory regions and associated with overexpressed genes suggests a significant role for 5hmC in IDH1 mutant HGG.
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Correction: Study protocol for a randomised controlled trial: harmonising optimal strategy for treatment of coronary artery stenosis -- coronary intervention with next-generation drug-eluting stent platforms and abbreviated dual antiplatelet therapy (HOST-IDEA) trial
Kim C, Han J, Yang H, et al. Study protocol for a randomised controlled trial: harmonising optimal strategy for treatment of coronary artery stenosis — coronary intervention with next-generation drug-eluting stent platforms and abbreviated dual antiplatelet therapy (HOST-IDEA) trial. BMJ Open 2017;7:e016617. doi: 10.1136/bmjopen-2017-016617
The author name 'Kyu-Rock Han' should be spelled 'Kyoo-Rok Han'.
http://ift.tt/2BliFR5
Does assistive technology contribute to social inclusion for people with intellectual disability? A systematic review protocol
Introduction
The aim of this review is to answer the following question: Does assistive technology contribute to social inclusion for people with intellectual disability? Previous research on assistive technology has focused on socioeconomic impacts such as education, employment and access to healthcare by people with intellectual disability. There is a need to consolidate evidence on the interaction between intellectual disability, assistive technology, community living and social inclusion.
Methods and analysisThe review will consider studies from all settings: geographical, socioeconomic and care (institutional and community care), published in English. Studies reported in other languages with abstracts in English will be included if they can be translated using Google Translate, otherwise such studies will be included in the appendix. The review will include both qualitative and quantitative studies. The intervention in this review refers to the use of assistive technology to promote community participation or interpersonal relationships (social inclusion) for people with intellectual disability. The outcomes will be behavioural and social benefits of using assistive technology by people with intellectual disability. Enhanced interpersonal relationships and community participation by people with intellectual disability. Data analysis will be in two phases. The first phase will involve analysis of individual study designs separately. The second phase will be narrative/thematic synthesis of all study groups.
EthicsThe review will not create any ethical or safety concerns.
DisseminationAt least one peer-reviewed article in a leading journal such as the BMJ is planned. The findings will also be disseminated through a seminar session involving internal audience at Trinity College Dublin and within the Assistive Technologies for people with Intellectual Disability and Autism research programme.
PROSPERO registration numberCRD42017065447; Pre-results.
http://ift.tt/2BP4GnP
Severity and management of postabortion complications among women in Zimbabwe, 2016: a cross-sectional study
Objectives
Abortion complications cause significant morbidity and mortality. We aimed to assess the severity and factors associated with abortion complications (induced or spontaneous), and the management of postabortion care (PAC) in Zimbabwe.
DesignProspective, facility-based 28 day survey among women seeking PAC and their providers.
Setting127 facilities in Zimbabwe with the capacity to provide PAC, including all central and provincial hospitals, and a sample of primary health centres (30%), district/general/mission hospitals (52%), private (77%) and non-governmental organisation (NGO) (68%) facilities.
Participants1002 women presenting with abortion complications during the study period.
Main outcome measuresSeverity of abortion complications and associated factors, delays in care seeking, and clinical management of complications.
ResultsOverall, 59% of women had complications classified as mild, 19% as moderate, 19% as severe, 3% as near miss and 0.2% died. A median of 47 hours elapsed between experiencing complication and receiving treatment; many delays were due to a lack of finances. Women who were rural, younger, not in union, less educated, at later gestational ages or who had more children were significantly more likely to have higher severity complications. Most women were treated by doctors (91%). The main management procedure used was dilatation and curettage/dilatation and evacuation (75%), while 12% had manual vacuum aspiration (MVA) or electrical vacuum aspiration and 11% were managed with misoprostol. At discharge, providers reported that 43% of women received modern contraception.
ConclusionZimbabwean women experience considerable abortion-related morbidity, particularly young, rural or less educated women. Abortion-related morbidity and concomitant mortality could be reduced in Zimbabwe by liberalising the abortion law, providing PAC in primary health centres, and training nurses to use medical evacuation with misoprostol and MVA. Regular in-service training on PAC guidelines with follow-up audits are needed to ensure compliance and availability of equipment, supplies and trained staff.
http://ift.tt/2BiA7G5
Outcomes comparison of different surgical strategies for the management of severe aortic valve stenosis: study protocol of a prospective multicentre European registry (E-AVR registry)
Introduction
Traditional and transcatheter surgical treatments of severe aortic valve stenosis (SAVS) are increasing in parallel with the improved life expectancy. Recent randomised controlled trials (RCTs) reported comparable or non-inferior mortality with transcatheter treatments compared with traditional surgery. However, RCTs have the limitation of being a mirror of the predefined inclusion/exclusion criteria, without reflecting the 'real clinical world'. Technological improvements have recently allowed the development of minimally invasive surgical accesses and the use of sutureless valves, but their impact on the clinical scenario is difficult to assess because of the monocentric design of published studies and limited sample size. A prospective multicentre registry including all patients referred for a surgical treatment of SAVS (traditional, through full sternotomy; minimally invasive; or transcatheter; with both 'sutured' and 'sutureless' valves) will provide a 'real-world' picture of available results of current surgical options and will help to clarify the 'grey zones' of current guidelines.
Methods and analysisEuropean Aortic Valve Registry is a prospective observational open registry designed to collect all data from patients admitted for SAVS, with or without coronary artery disease, in 16 cardiac surgery centres located in six countries (France, Germany, Italy, Spain, Switzerland and UK). Patients will be enrolled over a 2-year period and followed up for a minimum of 5 years to a maximum of 10 years after enrolment. Outcome definitions are concordant with Valve Academic Research Consortium-2 criteria and established guidelines. Primary outcome is 5-year all-cause mortality. Secondary outcomes aim at establishing 'early' 30-day all-cause and cardiovascular mortality, as well as major morbidity, and 'late' cardiovascular mortality, major morbidity, structural and non-structural valve complications, quality of life and echocardiographic results.
Ethics and disseminationThe study protocol is approved by local ethics committees. Any formal presentation or publication of data will be considered as a joint publication by the participating physician(s) and will follow the recommendations of the International Committee of Medical Journal Editors for authorship.
Trial registration numberNCT03143361; Pre-results.
http://ift.tt/2BRlB9t
Protocol for validation of the 4AT, a rapid screening tool for delirium: a multicentre prospective diagnostic test accuracy study
Introduction
Delirium is a severe neuropsychiatric syndrome of rapid onset, commonly precipitated by acute illness. It is common in older people in the emergency department (ED) and acute hospital, but greatly under-recognised in these and other settings. Delirium and other forms of cognitive impairment, particularly dementia, commonly coexist. There is a need for a rapid delirium screening tool that can be administered by a range of professional-level healthcare staff to patients with sensory or functional impairments in a busy clinical environment, which also incorporates general cognitive assessment. We developed the 4 'A's Test (4AT) for this purpose. This study's primary objective is to validate the 4AT against a reference standard. Secondary objectives include (1) comparing the 4AT with another widely used test (the Confusion Assessment Method (CAM)); (2) determining if the 4AT is sensitive to general cognitive impairment; (3) assessing if 4AT scores predict outcomes, including (4) a health economic analysis.
Methods and analysis900 patients aged 70 or over in EDs or acute general medical wards will be recruited in three sites (Edinburgh, Bradford and Sheffield) over 18 months. Each patient will undergo a reference standard delirium assessment and will be randomised to assessment with either the 4AT or the CAM. At 12 weeks, outcomes (length of stay, institutionalisation and mortality) and resource utilisation will be collected by a questionnaire and via the electronic patient record.
Ethics and disseminationEthical approval was granted in Scotland and England. The study involves administering tests commonly used in clinical practice. The main ethical issues are the essential recruitment of people without capacity. Dissemination is planned via publication in high impact journals, presentation at conferences, social media and the website www.the4AT.com.
Trial registration numberISRCTN53388093; Pre-results.
http://ift.tt/2BiA3Gl
Adaptive design clinical trials: a review of the literature and ClinicalTrials.gov
Objectives
This review investigates characteristics of implemented adaptive design clinical trials and provides examples of regulatory experience with such trials.
DesignReview of adaptive design clinical trials in EMBASE, PubMed, Cochrane Registry of Controlled Clinical Trials, Web of Science and ClinicalTrials.gov. Phase I and seamless Phase I/II trials were excluded. Variables extracted from trials included basic study characteristics, adaptive design features, size and use of independent data monitoring committees (DMCs) and blinded interim analyses. We also examined use of the adaptive trials in new drug submissions to the Food and Drug Administration (FDA) and European Medicines Agency (EMA) and recorded regulators' experiences with adaptive designs.
Results142 studies met inclusion criteria. There has been a recent growth in publicly reported use of adaptive designs among researchers around the world. The most frequently appearing types of adaptations were seamless Phase II/III (57%), group sequential (21%), biomarker adaptive (20%), and adaptive dose-finding designs (16%). About one-third (32%) of trials reported an independent DMC, while 6% reported blinded interim analysis. We found that 9% of adaptive trials were used for FDA product approval consideration, and 12% were used for EMA product approval consideration. International regulators had mixed experiences with adaptive trials. Many product applications with adaptive trials had extensive correspondence between drug sponsors and regulators regarding the adaptive designs, in some cases with regulators requiring revisions or alterations to research designs.
ConclusionsWider use of adaptive designs will necessitate new drug application sponsors to engage with regulatory scientists during planning and conduct of the trials. Investigators need to more consistently report protections intended to preserve confidentiality and minimise potential operational bias during interim analysis.
http://ift.tt/2BRlw5F
Correction: Bluebelle study (phase A): a mixed-methods feasibility study to inform an RCT of surgical wound dressing strategies
The Bluebelle Study Group, the Severn and Peninsula Audit and Research Collaborative for Surgeons, and the West Midlands Research Collaborative. Bluebelle study (phase A): a mixed-methods feasibility study to inform an RCT of surgical wound dressing strategies. BMJ Open 2016;6:e012635. doi: 10.1136/bmjopen-2016-012635
The study group for this research agreed a collaborative authorship policy, as stated in the title of the manuscript. The author byline should have read:
Rooshenas L, The Bluebelle Study Group, the Severn and Peninsula Audit and Research Collaborative for Surgeons, and the West Midlands Research Collaborative.
http://ift.tt/2BiA25f
Association between social health insurance and choice of hospitals among internal migrants in China: a national cross-sectional study
Objectives
There is a tendency to pursue higher-level hospitalisation services in China, especially for internal migrants. This study aims to investigate the choices of hospitalisation services among internal migrants, and evaluate the association between social health insurance and hospitalisation choices.
MethodsData were from a 2014 nationally representative cross-sectional sample of internal migrants aged 15–59 years in China. Descriptive analyses were used to perform the distribution of healthcare facility levels for hospitalisation services, and multinomial logistic regression was applied to examine the association between social health insurance and hospitalisation choices.
ResultsOf the 6121 inpatient care users, only 11.50% chose the primary healthcare facilities for hospitalisation services, 44.91% chose the secondary hospitals and 43.59% preferred the tertiary hospitals. The choices presented large regional variations across the country. Compared with the uninsured, social health insurance had no statistically significant effect on patient choices of healthcare facility levels among internal migrants in China, whereas socioeconomic status was positively associated with the choices.
ConclusionsSocial health insurance had little influence on the hospital choice among the internal migrants. Thus, social health insurance should be consolidated and portable to enhance the proper incentive of health insurance on healthcare seeking behaviours.
http://ift.tt/2BOpNqc
Interventions to increase access to or uptake of physical health screening in people with severe mental illness: a realist review
Objectives
To identify and evaluate interventions aimed at increasing uptake of, or access to, physical health screening by adults with severe mental illness; to examine why interventions might work.
DesignRealist review.
SettingPrimary, secondary and tertiary care.
ResultsA systematic search identified 1448 studies, of which 22 met the inclusion criteria. Studies were from Australia (n=3), Canada (n=1), Hong Kong (n=1), UK (n=11) and USA (n=6). The studies focused on breast cancer screening, infection preventive services and metabolic syndrome (MS) screening by targeting MS-related risk factors. The interventions could be divided into those focusing on (1) health service delivery changes (12 studies), using quality improvement, randomised controlled trial, cluster randomised feasibility trial, retrospective audit, cross-sectional study and satisfaction survey designs and (2) tests of tools designed to facilitate screening (10 studies) using consecutive case series, quality improvement, retrospective evaluation and pre–post audit study designs. All studies reported improved uptake of screening, or that patients had received screening they would not have had without the intervention. No estimation of overall effect size was possible due to heterogeneity in study design and quality. The following factors may contribute to intervention success: staff and stakeholder involvement in screening, staff flexibility when taking physical measurements (eg, using adapted equipment), strong links with primary care and having a pharmacist on the ward.
ConclusionsA range of interventions may be effective, but better quality research is needed to determine any effect size. Researchers should consider how interventions may work when designing and testing them in order to target better the specific needs of this population in the most appropriate setting. Behaviour-change interventions to reduce identified barriers of patient and health professional resistance to screening this population are required. Resource constraints, clarity over professional roles and better coordination with primary care need to be addressed.
http://ift.tt/2BizYT3
Is socioeconomic segregation of the poor associated with higher premature mortality under the age of 60? A cross-sectional analysis of survey data in major Indian cities
Objectives
Although urbanisation is generally associated with poverty reduction in low-income and middle-income countries, it also results in increased socioeconomic segregation of the poor. Cities with higher levels of socioeconomic segregation tend to have higher mortality rates, although the evidence is based on ecological associations. The paper examines whether socioeconomic segregation of the poor is associated with higher under-60 years ('premature') mortality risk in Indian cities and whether this association is confounded by contextual and compositional sociodemographic and socioeconomic factors.
Setting and participantsA population representative sample of over one million from 39 427 households living in 1876 urban wards within 59 Indian districts (cities) from the third (2008) District Level Household Survey (DLHS-3).
Primary outcome and other measuresThe outcome was any death under the age of 60 reported by households in the preceding 4years of the DLHS-3. Socioeconomic segregation, estimated at the district (city) level, was measured using an isolation index of the poor and the index of dissimilarity.
ResultsPoor households living in cities where the poor were more isolated had higher probabilities of premature mortality than poor households living in cities where the poor were less isolated. In contrast, it did not matter whether rich households lived in more or less socioeconomically segregated cities. A 1 SD increase in the isolation index was associated with an absolute increase of 1.1% in the probability of premature mortality for the poorest households.
ConclusionIncreasing segregation of the poor may result in higher premature mortality. As low-income and middle-income countries become increasingly urbanised, there is a risk that this may lead to increased segregation of the poor as well as increased premature mortality.
http://ift.tt/2BRloDd
Sequelae of multidrug-resistant tuberculosis: protocol for a systematic review and meta-analysis
Introduction
The sequelae of multidrug-resistant tuberculosis (MDR-TB) are poorly understood and inconsistently reported. We will aim to assess the existing evidence for the clinical, psychological, social and economic sequelae of MDR-TB and to assess the health-related quality of life in patients with MDR-TB.
Methods and analysisWe will perform a systematic review and meta-analysis of published studies reporting sequelae of MDR-TB. We will search PubMed, SCOPUS, ProQuest, Web of Science and PsychINFO databases up to 5 September 2017. MDR-TB sequelae will include any clinical, psychological, social and economic effects as well as health-related quality of life that occur after MDR-TB treatment or illness. Two researchers will screen the titles and abstracts of all citations identified in our search, extract data, and assess the scientific quality using standardised formats. Providing there is appropriate comparability in the studies, we will use a random-effects meta-analysis model to produce pooled estimates of MDR-TB sequelae from the included studies. We will stratify the analyses based on treatment regimen, comorbidities (such as HIV status and diabetes mellitus), previous TB treatment history and study setting.
Ethics and disseminationAs this study will be based on published data, ethical approval is not required. The final report will be disseminated through publication in a peer-reviewed scientific journal and will also be presented at relevant conferences.
PROSPERO registration numberhttp://ift.tt/2Blz6wI
Risk factors and between-hospital variation of caesarean section in Denmark: a cohort study
Objectives
The aim of this study was to estimate the effects of risk factors on elective and emergency caesarean section (CS) and to estimate the between-hospital variation of risk-adjusted CS proportions.
DesignHistorical registry-based cohort study.
Settings and participantsThe study was based on all singleton deliveries in hospital units in Denmark from January 2009 to December 2012. A total of 226 612 births by 198 590 mothers in 29 maternity units were included.
Primary and secondary outcome measuresWe estimated (1) OR of elective and emergency CS adjusted for several risk factors, for example, body mass index, parity, age and size of maternity unit and (2) risk-adjusted proportions of elective and emergency CS to evaluate between-hospital variation.
ResultsThe CS proportion was stable at 20%–21%, but showed wide variation between units, even in adjusted models. Large units performed significantly more elective CSs than smaller units, and the risk of emergency CS was significantly reduced compared with smaller units. Many of the included risk factors were found to influence the risk of CS. The most important risk factors were breech presentation and previous CS. Four units performed more CSs and one unit fewer CSs than expected.
ConclusionThe main risk factors for elective CS were breech presentation and previous CS; for emergency CS they were breech presentation and cephalopelvic disproportion. The proportions of CS were stable during the study period. We found variation in risk-adjusted CS between hospitals in Denmark. Although exhaustive models were applied, the results indicated the presence of systematic variation between hospital units, which was unexpected in a small, well-regulated country such as Denmark.
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Standard echocardiography versus handheld echocardiography for the detection of subclinical rheumatic heart disease: protocol for a systematic review
Introduction
Rheumatic heart disease (RHD) is a preventable and treatable chronic condition which persists in many developing countries largely affecting impoverished populations. Handheld echocardiography presents an opportunity to address the need for more cost-effective methods of diagnosing RHD in developing countries, where the disease continues to carry high rates of morbidity and mortality. Preliminary studies have demonstrated moderate sensitivity as well as high specificity and diagnostic odds for detecting RHD in asymptomatic patients. We describe a protocol for a systematic review on the diagnostic performance of handheld echocardiography compared to standard echocardiography using the 2012 World Heart Federation criteria for diagnosing subclinical RHD.
Methods and analysisElectronic databases including PubMed, Scopus, Web of Science and EBSCOhost as well as reference lists and citations of relevant articles will be searched from 2012 to date using a predefined strategy incorporating a combination of Medical Subject Heading terms and keywords. The methodological validity and quality of studies deemed eligible for inclusion will be assessed against review specific Quality Assessment of Diagnostic Accuracy Studies 2 criteria and information on metrics of diagnostic accuracy and demographics extracted. Forest plots of sensitivity and specificity as well as scatter plots in receiver operating characteristic (ROC) space will be used to investigate heterogeneity. If possible, a meta-analysis will be conducted to produce summary results of sensitivity and specificity using the Hierarchical Summary ROC method. In addition, a sensitivity analysis will be conducted to investigate the effect of studies with a high risk of bias.
Ethics and disseminationEthics approval is not required for this systematic review of previously published literature. The planned review will provide a summary of the diagnostic accuracy of handheld echocardiography. Results may feed into evidence-based guidelines and should the findings of this review warrant a change in clinical practice, a summary report will be disseminated among leading clinicians and healthcare professionals in the field.
PROSPERO registration numberhttp://ift.tt/2BkS1b3
Multicentre study on capsular closure versus non-capsular closure during hip arthroscopy in Danish patients with femoroacetabular impingement (FAI): protocol for a randomised controlled trial
Introduction
Hip arthroscopy has become a standard procedure in the treatment of hip joint pain not related to osteoarthritis or dysplasia in the young and active patient. There has been increasing focus on the contribution of the hip capsule to function and on stability following hip arthroscopy. It has been suggested that capsular closure after hip arthroscopy may prevent microinstability and macroinstability of the hip joint and reduce revision rate. However, it remains unknown whether capsular closure should be performed as a standard procedure when performing hip arthroscopies, especially in patients without additional risk factors for instability such as hypermobility or dysplasia of the hip. We hypothesised that capsular closure will lead to a superior outcome in hip arthroscopy for femoroacetabular impingement syndrome (FAIS) compared with non-capsular closure.
Methods and analysisIn this randomised controlled, multicentre trial, 200 patients scheduled for hip arthroscopy for FAIS will be cluster randomised into one of two groups (group I: hip arthroscopy without capsular closure, group II: hip arthroscopy combined with capsular closure). Inclusion criteria are: age between 18 years and 50 years and FAIS according to the Warwick agreement. Exclusion criteria are: previous hip surgery in either hip, previous conditions of Legg-Calvé-Perthes or slipped capital femoral epiphysis, malignant disease, recent hip or pelvic fractures, arthritis, Ehlers-Danlos or Marfan disease, recent (within 6 weeks) application of intra-articular corticosteroids, language problems of any kind, and radiological signs of osteoarthritis, acetabular dysplasia or acetabular retroversion. Surgery will be performed in Denmark at four centres by four surgeons, all performing an interportal capsulotomy and closure with at least two absorbable sutures. Patients in both groups, who are blinded for the intervention, will receive the same standardised rehabilitation programme. As primary outcome scores, HAGOS (sport) will be used with HAGOS (symptoms, pain, function in daily living, participation in physical activities and hip and/or groin-related quality of life), Hip Sports Activity Scale, short validated version of the International Hip Outcome Tool, EQ-5D, Visual Analogue Scale for pain, complications and reoperation rate as secondary outcome tools. Using HAGOS (sport) as primary outcome parameter the power analysis required a minimum of 84 individuals per group. Together with a clinical examination performed by the patient's surgeon 1 year after surgery, patient reported outcome measures will be completed preoperatively, as well as at 3 months, 1 year, 2 years and 5 years postoperatively. In addition, adverse effects will be recorded.
Ethics and disseminationThe study is approved by the Central Denmark Region Committee on Biomedical research ethics. The results of this study will be presented at national and international congresses and published in peer-reviewed journals.
Trial registration numberNCT03158454; Pre-results.
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Correction: Epidural analgesia in critically ill patients with acute pancreatitis: the multicentre randomised controlled EPIPAN study protocol
Bulyez S, Pereira B, Caumon E, et al. Epidural analgesia in critically ill patients with acute pancreatitis: the multicentre randomised controlled EPIPAN study protocol. BMJ Open 2017;7:e015280. doi: 10.1136/bmjopen-2016-015280.
The list of Collaborators (EPIPAN study group) was missed off the article. This list should read:
Collaborators Sophie Kauffmann, Florian Grimaldi, Charlotte Fernandez-Canal, Philippe Chevaldonné, Julien Pascal, Renaud Guérin, Sébastien Perbet, Sophie Cayot, Thomas Godet, Sophiano Radji, Camille Verlhac, Sandrine Thibault, Christine Rolhion, Justine Bourdier, Emmanuel Futier, Jean-Etienne Bazin, Laetitia Sturma (CHU Clermont-Ferrand, Clermont-Ferrand, France); Lydie Marie-Anne, Olivier Windisch (Geneva university hospitals, Geneva, Switzerland); Annick Puchois, Cyril Boronad, Marine Agullo (Cannes general hospital, Cannes, France); Boris Jung, Gérald Chanques, Cécile Spirito, Albert Prades, Cisse Moussa, Anne Verchere, Claudine Gniadek, Fouad Belafia, Daniel Verzilli, Julie Carr, Audrey De Jong, Yannael Coisel, Jean-Marc Delay, Matthieu Conseil, Marie Gonzalez, Delphine Rosant (Montpellier university hospital, Montpellier, France); Michel Prevot (Nancy university hospital,...
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Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
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