- Erratum. [Journal Article]
- PMPer Med 2011; 8(6):692
- A retrospective study of opioid prescribing patterns at hospital discharge in surgical patients with obstructive sleep apnea. [Journal Article]
- CJCan J Anaesth 2018 May 18
- CONCLUSIONS: This study shows that surgical patients at risk for OSA or confirmed OSA are prescribed opioids at similar rates and doses upon discharge despite guidelines that recommend minimizing opioid use in OSA patients. These findings indicate a need to implement different strategies to reduce the prescription of opioids to patients with OSA.
- Cardiovascular Outcomes of PCSK9 Inhibitors: With Special Emphasis on Its Effect beyond LDL-Cholesterol Lowering. [Review]
- JLJ Lipids 2018; 2018:3179201
- PCSK9 inhibitors, monoclonal antibodies, are novel antihypercholesterolemic drugs. FDA first approved them in July 2015. PCSK9 protein (692-amino acids) was discovered in 2003. It plays a major role ...
PCSK9 inhibitors, monoclonal antibodies, are novel antihypercholesterolemic drugs. FDA first approved them in July 2015. PCSK9 protein (692-amino acids) was discovered in 2003. It plays a major role in LDL receptor degradation and is a prominent modulator in low-density lipoprotein cholesterol (LDL-C) metabolism. PCSK9 inhibitors are monoclonal antibodies that target PCSK9 protein in liver and inhibiting this protein leads to drastically lowering harmful LDL-C level in the bloodstream. Despite widespread use of the statin, not all the high-risk patients were able to achieve targeted level of LDL-C. Using PCSK9 inhibitors could lead to a substantial decrement in LDL-C plasma level ranging from 50% to 70%, either as a monotherapy or on top of statins. A large number of trials have shown robust reduction of LDL-C plasma level with the use of PCSK9 inhibitors as a monotherapy or in combination with statins in familial and nonfamilial forms of hypercholesterolemia. Moreover, PCSK9 inhibitors do not appear to increase the risk of hepatic and muscle-related side effects. PCSK9 inhibitors proved to be a highly potent and promising antihypercholesterolemic drug by decreasing LDL-R lysosomal degradation by PCSK9 protein. Statin drugs are known to have some pleiotropic effects. In this article, we are also focusing on the effects of PCSK9 inhibitor beyond LDL-C reduction like endothelial inflammation, atherosclerosis, its safety in patients with diabetes, obesity, and chronic kidney disease, and its influence on neurocognition and stroke.
- Azacitidine in the 'real-world': an evaluation of 1101 higher-risk myelodysplastic syndrome/low blast count acute myeloid leukaemia patients in Ontario, Canada. [Journal Article]
- BJBr J Haematol 2018 May 16
- The outcome of myelodysplastic syndrome (MDS) patients with uniformly higher-risk disease treated with azacitidine (AZA) in the 'real-world' remains largely unknown. We evaluated 1101 consecutive hig...
The outcome of myelodysplastic syndrome (MDS) patients with uniformly higher-risk disease treated with azacitidine (AZA) in the 'real-world' remains largely unknown. We evaluated 1101 consecutive higher-risk MDS patients (International Prognostic Scoring System intermediate-2/high) and low-blast count acute myeloid leukaemia (AML; 21-30% blasts) patients treated in Ontario, Canada. By dosing schedule, 24·7% received AZA for seven consecutive days, 12·4% for six consecutive days and 62·9% by 5-2-2. Overall, median number of cycles was 6 (range 1-67) and 8 (range 6-14) when restricted to the 692 (63%) patients who received at least 4 cycles. The actuarial median survival was 11·6 months [95% confidence interval (CI) 10·7-12·4) for the entire cohort and 18·0 months (landmark analysis; 95% CI 16·6-19·1 months) for those receiving at least 4 cycles. There was no difference in overall survival (OS) between the 3 dosing schedules (P = 0·87). In our large 'real-world' evaluation of AZA in higher-risk MDS/low-blast count AML, we demonstrated a lower than expected OS. Reassuringly, survival did not differ by dosing schedules. The OS was higher in the 2/3 of patients who received at least 4 cycles of treatment, reinforcing the necessity of sustained administration until therapeutic benefits are realised. This represents the largest 'real-world' evaluation of AZA in higher-risk MDS/low-blast count AML.
- Adenosine-Provoked Atrial Fibrillation Originating From Non-Pulmonary Vein Foci: The Clinical Significance and Outcome After Catheter Ablation. [Journal Article]
- JCJACC Clin Electrophysiol 2015; 1(3):127-135
- CONCLUSIONS: ATP provoked AF originating from non-PV foci under isoproterenol in 5.6% of patients undergoing paroxysmal AF ablation. ATP testing might be useful for identifying and eliminating AF originating from the SVC. The atria group was associated with a poor outcome after the last procedure despite efforts to eliminate non-PV foci.
- Injury and death during the ISIS occupation of Mosul and its liberation: Results from a 40-cluster household survey. [Journal Article]
- PMPLoS Med 2018; 15(5):e1002567
- CONCLUSIONS: Death and injuries during the military offensive to liberate Mosul considerably exceeded those during ISIS occupation. Airstrikes were the major reported cause of deaths, with the majority occurring in west Mosul. The extensive use of airstrikes and heavy artillery risks an extensive loss of life in densely populated urban areas. The high probability of survivor bias in this survey suggests that the actual number of injuries, kidnappings, and deaths in the neighborhoods sampled is likely to be higher than we report here.
- Diagnostic value of decoy receptor 3 combined with procalcitonin and soluble urokinase-type plasminogen activator receptor for sepsis. [Journal Article]
- CMCell Mol Biol Lett 2018; 23:22
- The levels of decoy receptor 3 (DcR3), soluble urokinase type plasminogen activator receptor (suPAR) and procalcitonin (PCT) are significantly increased in sepsis. We investigated the diagnostic valu...
The levels of decoy receptor 3 (DcR3), soluble urokinase type plasminogen activator receptor (suPAR) and procalcitonin (PCT) are significantly increased in sepsis. We investigated the diagnostic value of DcR3 combined with suPAR and PCT in sepsis. Patients with sepsis, non-infectious systemic inflammatory response comprehensive syndrome (SIRS) and healthy controls were recruited according to the diagnostic standard. We measured DcR3, suPAR, PCT, interleukin-6 (IL-6) and C-reactive protein (CRP), and the diagnostic value was evaluated by receiver operating characteristics (ROC) curves. In our analysis, serum DcR3, suPAR and PCT levels of the sepsis group were significantly higher than those of the SIRS and control groups. However, IL-6, CRP and WBC showed no significant difference between the SIRS group and the sepsis group. The serum DcR3 level was positively correlated with the serum suPAR level (r = 0.37, p = 0.0022) and PCT level (r = 0.37, p = 0.0021). Using DcR3, suPAR and PCT to distinguish SIRS from sepsis, the area under the curve (AUC) values were 0.892, 0.778 and 0.692. When DcR3, suPAR and PCT combined were used for diagnosis of sepsis, the AUC was 0.933, at a cut-off point of 0.342. This combination improved the sensitivity and specificity of diagnosis of sepsis, suggesting that use of the combination of three indexes enhanced the efficiency of sepsis diagnosis.
- Segregation mediated heterogeneous structure in a metastable β titanium alloy with a superior combination of strength and ductility. [Journal Article]
- SRSci Rep 2018 May 14; 8(1):7512
- In β titanium alloys, the β stabilizers segregate easily and considerable effort has been devoted to alleviate/eliminate the segregation. In this work, instead of addressing the segregation problems,...
In β titanium alloys, the β stabilizers segregate easily and considerable effort has been devoted to alleviate/eliminate the segregation. In this work, instead of addressing the segregation problems, the segregation was utilized to develop a novel microstructure consisting of a nanometre-grained duplex (α+β) structure and micrometre scale β phase with superior mechanical properties. An as-cast Ti-9Mo-6W alloy exhibited segregation of Mo and W at the tens of micrometre scale. This was subjected to cold rolling and flash annealing at 820 oC for 2 and 5 mins. The solidification segregation of Mo and W leads to a locally different microstructure after cold rolling (i.e., nanostructured β phase in the regions rich in Mo and W and plate-like martensite and β phase in regions relatively poor in Mo and W), which play a decisive role in the formation of the heterogeneous microstructure. Tensile tests showed that this alloy exhibited a superior combination of high yield strength (692 MPa), high tensile strength (1115 MPa), high work hardening rate and large uniform elongation (33.5%). More importantly, the new technique proposed in this work could be potentially applicable to other alloy systems with segregation problems.
- Autoantibody Signaling in Pemphigus Vulgaris: Development of an Integrated Model. [Review]
- FIFront Immunol 2018; 9:692
- Pemphigus vulgaris (PV) is an autoimmune skin blistering disease effecting both cutaneous and mucosal epithelia. Blister formation in PV is known to result from the binding of autoantibodies (autoAbs...
Pemphigus vulgaris (PV) is an autoimmune skin blistering disease effecting both cutaneous and mucosal epithelia. Blister formation in PV is known to result from the binding of autoantibodies (autoAbs) to keratinocyte antigens. The primary antigenic targets of pathogenic autoAbs are known to be desmoglein 3, and to a lesser extent, desmoglein 1, cadherin family proteins that partially comprise the desmosome, a protein structure responsible for maintaining cell adhesion, although additional autoAbs, whose role in blister formation is still unclear, are also known to be present in PV patients. Nevertheless, there remain large gaps in knowledge concerning the precise mechanisms through which autoAb binding induces blister formation. Consequently, the primary therapeutic interventions for PV focus on systemic immunosuppression, whose side effects represent a significant health risk to patients. In an effort to identify novel, disease-specific therapeutic targets, a multitude of studies attempting to elucidate the pathogenic mechanisms downstream of autoAb binding, have led to significant advancements in the understanding of autoAb-mediated blister formation. Despite this enhanced characterization of disease processes, a satisfactory explanation of autoAb-induced acantholysis still does not exist. Here, we carefully review the literature investigating the pathogenic disease mechanisms in PV and, taking into account the full scope of results from these studies, provide a novel, comprehensive theory of blister formation in PV.
New Search Next
- Serum Amino Acid Profiling in Patients with Alkaptonuria Before and After Treatment with Nitisinone. [Journal Article]
- JRJIMD Rep 2018 May 13
- CONCLUSIONS: Marked hypertyrosinaemia was observed following treatment with nitisinone. Noteworthy changes were also observed in the ratio of several amino acids following treatment with nitisinone suggesting that the availability of amino acids for neurotransmitter biosynthesis and liver function may be altered following treatment with nitisinone.