Hoganconnolly7063

The objective was to assess predictors for unfavorable neurological outcome (UO) in out-of-hospital (OHCA) and in-hospital (IHCA) cardiac arrest patients treated with Extracorporeal cardiopulmonary resuscitation (ECPR).

A post hoc analysis of retrospective data from five European ECPR centers (January 2012-December 2016) was performed. The primary composite endpoint was 3-month UO defined as survival with a cerebral performance category (CPC) of 3-4 or death (CPC 5).

A total of 413 patients treated with ECPR were included (median age was 57 [48-65] years, male gender 78%) 61% of patients (n=250) suffered OHCA. The median time from collapse to ECMO placement was 63 [45-82] minutes. Overall, 81% patients (n=333) showed unfavorable UO, which was higher in OHCA patients (90% vs 66%), as compared to IHCA. In OHCA, prolonged time from collapse to ECMO initiation (OR 1.02, p<0.01) and higher ECMO blood flow (OR 1.99, p=0.01) were associated with UO while initial shockable rhythm (OR 0.04, p<0.01), previous heart disease (OR 0.20, p<0.01) and pre-hospital hypothermia (OR 0.08, p<0.01) had a protective role. In IHCA, prolonged time from arrest to ECMO implantation (OR 1.02, p=0.03), high lactate level on admission (OR 1.15, p<0.01) and higher body weight (OR 1.03, p<0.01) were independently associated with UO.

IHCA and OHCA patients receiving ECPR have different predictors of UO at presentation, suggesting that selection criteria for ECPR should be decided according to the location of CA. After ECMO initiation, ECMO blood flow management and mean arterial pressure targets might also impact neurological recovery.

IHCA and OHCA patients receiving ECPR have different predictors of UO at presentation, suggesting that selection criteria for ECPR should be decided according to the location of CA. After ECMO initiation, ECMO blood flow management and mean arterial pressure targets might also impact neurological recovery.

One percent to 3% of contemporary non-cemented total hip arthroplasties (THAs) present with symptomatic mechanically assisted crevice corrosion (MACC). The incidence of this problem, however, as well as the rate of asymptomatic elevations in serum cobalt, is unknown.

Cobalt and chromium levels were obtained in conjunction with radiographs at routine 10-year surveillance follow-up of THAs from a single manufacturer with a titanium stem, cobalt alloy femoral head, and cross-linked polyethylene countersurface.

Ten-year follow-up of patients with 162 consecutive THAs revealed that 17 patients with 18 hips had died of unrelated causes prior to metal ion testing. Two hips were revised for other reasons, and of the remaining 142 hips, 33 were in patients who were lost, leaving 109 hips (77% of those in alive patients and unrevised for other reasons and 67% of the entire cohort) for investigation. Sixty-three patients (58%) had a serum cobalt less than 1 ppb, and 35 (32%) a cobalt of ≥1 ppb, a cutoff consistent with MACC. Of the 32 hips with definite MACC, 15 of 32 (47%) patients were symptomatic, 16 of 30 (53%) patients had adverse local tissue reaction on magnetic resonance imaging, and 19 of 32 (59%) patients have undergone revision surgery for MACC to date.

At 10-year follow-up, a minimum of 22% (35/162) hips had a cobalt level more than 1 ppb, consistent with MACC. Symptoms and adverse local tissue reactions are each present about one-half of the time, and 59% of those with documented MACC have undergone revision.

At 10-year follow-up, a minimum of 22% (35/162) hips had a cobalt level more than 1 ppb, consistent with MACC. Symptoms and adverse local tissue reactions are each present about one-half of the time, and 59% of those with documented MACC have undergone revision.

Hip instability following total hip arthroplasty (THA) can be a major cause of revision surgery. Physiological patient position impacts acetabular anteversion and abduction, and influences the functional component positioning. Osteoarthritis of the spine leads to abnormal spinopelvic biomechanics and motion, but there is no consensus on the degree of component variability for THAs performed by anterior approach. Therefore, we sought to present guidelines for changes in acetabular component positioning between supine and standing positions for patients undergoing primary THA by a uniform anterior approach.

Perioperative patient radiographs of the pelvis and lumbar spine were collected. Images were used to determine acetabular component positioning and degree of coexisting spinal pathology, categorized as a Lane Grade (LG). Final analysis of variance was performed on a sample size of 643 anterior primary THAs.

From supine to standing position, as the severity of lumbar pathology increased the change in anteversion also increased (LG0=-0.11° ± 4.65°, LG1= 2.02° ± 4.09°, LG2-3= 5.78° ± 5.72°, P < .001). The mean supine anteversion in patients with absent lumbar pathology was 19.72° ± 5.05° and was lower in patients with worsening lumbar pathology (LG1= 18.25° ± 4.81°, LG2-3= 16.73° ± 5.28°, P < .001).

Patients undergoing primary THA by anterior approach with worsening spinal pathology have larger increases in component anteversion when transitioning from supine to standing positions. Consideration should be given to this expected variability when placing the patient's acetabular component.

Patients undergoing primary THA by anterior approach with worsening spinal pathology have larger increases in component anteversion when transitioning from supine to standing positions. Consideration should be given to this expected variability when placing the patient's acetabular component.

We evaluated the reliability of intraoperative assessment of leukocyte esterase (LE) in synovial fluid samples from patients undergoing reimplantation following implant removal and spacer insertion for periprosthetic joint infection (PJI). Our hypothesis was that a positive intraoperative LE test would be a better predictor of persistent infection than either serum C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) or the combination of serum CRP and ESR.

The records of 76 patients who received a 2-stage exchange for PJI were retrospectively reviewed. Synovial fluid was collected for LE measurement during surgery before arthrotomy in 79 procedures. Receiver operating characteristic curves were generated. Sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and area under the curve (AUC) of LE, CRP, ESR, and CRP+ ESR were calculated.

Sensitivity, specificity, positive predictive value, and negative predictive value of the LE assay were 82%, 99%, 90%, and 97%, respectively. Receiver operating characteristic analysis revealed an LE threshold of 1.5 between the first (negative) and the second (positive) level of the ordinal variable, so that a grade starting from 1+ was accurate for a diagnosis of persistent infection (AUC 0.9044). The best thresholds for the CRP and the ESR assay were 8.25 mg/L (82% sensitivity, 84% specificity, AUC 0.8416) and 45 mm/h (55% sensitivity, 87% specificity, AUC 0.7493), respectively.

The LE strip test proved a reliable tool to diagnose persistence of infection and outperformed the serum CRP and ESR assays. The strip test provides a valuable intraoperative diagnostic during second-stage revision for PJI.

The LE strip test proved a reliable tool to diagnose persistence of infection and outperformed the serum CRP and ESR assays. The strip test provides a valuable intraoperative diagnostic during second-stage revision for PJI.The cancer cell mitochondrion is functionally different from that in normal cells and could be targeted to develop novel experimental therapeutics. The aryl-ureido fatty acid CTU (16([4-chloro-3-(trifluoromethyl)phenyl]-carbamoylamino)hexadecanoic acid) is the prototype of a new class of mitochondrion-targeted agents that kill cancer cells. Here we show that CTU rapidly depolarized the inner mitochondrial membrane, selectively inhibited complex III of the electron transport chain and increased reactive oxygen species (ROS) production. From RNA-seq analysis, endoplasmic reticulum (ER)-stress was a major activated pathway in CTU-treated cells and in MDA-MB-231 tumor xenografts from CTU-treated nu/nu mice. Mitochondrion-derived ROS activated the PERK-linked ER-stress pathway and induced the BH3-only protein NOXA leading to outer mitochondrial membrane (OMM) disruption. The lipid peroxyl scavenger α-tocopherol attenuated CTU-dependent ER-stress and apoptosis which confirmed the critical role of ROS. Oleic acid protected against CTU-mediated apoptosis by activating Mcl-1 expression, which increased NOXA sequestration and prevented OMM disruption. Taken together, CTU both uncouples mitochondrial electron transport and activates ROS production which promotes ER-stress-dependent OMM disruption and tumor cell death. Dual-mitochondrial targeting agents like CTU offer a novel approach for development of new anti-cancer therapeutics.In recent years, many research groups have begun to utilize bioengineered in vitro models of cancer to study mechanisms of disease progression, test drug candidates, and develop platforms to advance personalized drug treatment options. click here Due to advances in cell and tissue engineering over the last few decades, there are now a myriad of tools that can be used to create such in vitro systems. In this review, we describe the considerations one must take when developing model systems that accurately mimic the in vivo tumor microenvironment (TME) and can be used to answer specific scientific questions. We will summarize the importance of cell sourcing in models with one or multiple cell types and outline the importance of choosing biomaterials that accurately mimic the native extracellular matrix (ECM) of the tumor or tissue that is being modeled. We then provide examples of how these two components can be used in concert in a variety of model form factors and conclude by discussing how biofabrication techniques such as bioprinting and organ-on-a-chip fabrication can be used to create highly reproducible complex in vitro models. Since this topic has a broad range of applications, we use the final section of the review to dive deeper into one type of cancer, glioblastoma, to illustrate how these components come together to further our knowledge of cancer biology and move us closer to developing novel drugs and systems that improve patient outcomes.Lung cancer (LC) is often diagnosed at an advanced stage and conventional treatments for disease management have limitations associated with them. Novel therapeutic targets are thus avidly sought for the effective management of LC. RNA binding proteins (RBPs) have been convincingly established as key players in tumorigenesis, and their dysregulation is linked to multiple cancers, including LC. In this context, we review the role of Human antigen R (HuR), an RBP that is overexpressed in LC, and further associated with various aspects of LC tumor growth and response to therapy. Herein, we describe the role of HuR in LC progression and outline the evidences supporting various pharmacologic and biologic approaches for inhibiting HuR expression and function. These approaches, including use of small molecule inhibitors, siRNAs and shRNAs, have demonstrated favorable results in reducing tumor cell growth, invasion and migration, angiogenesis and metastasis. Hence, HuR has significant potential as a key therapeutic target in LC.