Carilion Roanoke Memorial Hospital

BACKGROUND: As ongoing research explores the impact of moral distress on health care professionals (HCPs) and organizations and seeks to develop effective interventions, valid and reliable instruments to measure moral distress are needed. This article describes the development and testing of a revision of the widely used Moral Distress Scale-Revised (MDS-R) to measure moral distress. METHODS: We revised the MDS-R by evaluating the combined data from 22 previous studies, assessing 301 write-in items and 209 root causes identified through moral distress consultation, and reviewing 14 recent publications from various professions in which root causes were described. The revised 27-item scale, the Measure of Moral Distress for Healthcare Professionals (MMD-HP), is usable by all HCPs in adult and pediatric critical, acute, or long-term acute care settings. We then assessed the reliability of the MMD-HP and evaluated construct validity via hypothesis testing. The MMD-HP, Hospital Ethical Climate Survey (HECS), and a demographic survey were distributed electronically via Qualtrics to nurses, physicians, and other health care professionals at two academic medical centers over a 3-week period. RESULTS: In total, 653 surveys were included in the final analysis. The MMD-HP demonstrated good reliability. The four hypotheses were supported: (1) MMD-HP scores were higher for nurses (M 112.3, SD 73.2) than for physicians (M 96.3, SD 54.7, p = 0.023). (2) MMD-HP scores were higher for those considering leaving their position (M 168.4, SD 75.8) than for those not considering leaving (M 94.3, SD 61.2, p < 0.001). (3) The MMD-HP was negatively correlated with the HECS (r = -0.55, p < 0.001). (4) An exploratory factor analysis revealed a four-factor structure, reflective of patient, unit, and system levels of moral distress. CONCLUSIONS: The MMD-HP represents the most currently understood causes of moral distress. Because the instrument behaves as would be predicted, we recommend that the MMD-HP replace the MDS-R.

Myocardial infarction is a prevalent major cardiovascular event that arises from myocardial ischemia with or without reperfusion, and basic and translational research is needed to better understand its underlying mechanisms and consequences for cardiac structure and function. Ischemia underlies a broad range of clinical scenarios ranging from angina to hibernation to permanent occlusion, and while reperfusion is mandatory for salvage from ischemic injury, reperfusion also inflicts injury on its own. In this consensus statement, we present recommendations for animal models of myocardial ischemia and infarction. With increasing awareness of the need for rigor and reproducibility in designing and performing scientific research to ensure validation of results, the goal of this review is to provide best practice information regarding myocardial ischemia-reperfusion and infarction models. Listen to this article's corresponding podcast at ajpheart.podbean.com/e/guidelines-for-experimental-models-of-myocardial-ischemia-and-infarction/.

PURPOSE: Moral distress is a phenomenon affecting many professionals across healthcare settings. Few studies have used a standard measure of moral distress to assess and compare differences among professions and settings. DESIGN: A descriptive, comparative design was used to study moral distress among all healthcare professionals and all settings at one large healthcare system in January 2011. METHODS: Data were gathered via a web-based survey of demographics, the Moral Distress Scale-Revised (MDS-R), and a shortened version of Olson's Hospital Ethical Climate Scale (HECS-S). FINDINGS: Five hundred ninety-two (592) clinicians completed usable surveys (22%). Moral distress was present in all professional groups. Nurses and other professionals involved in direct patient care had significantly higher moral distress than physicians (p = .001) and other indirect care professionals (p < .001). Moral distress was negatively correlated with ethical workplace climate (r = -0.516; p < .001). Watching patient care suffer due to lack of continuity and poor communication were the highest-ranked sources of moral distress for all professional groups, but the groups varied in other identified sources. Providers working in adult or intensive care unit (ICU) settings had higher levels of moral distress than did clinicians in pediatric or non-ICU settings (p < .001). Providers who left or considered leaving a position had significantly higher moral distress levels than those who never considered leaving (p < .001). Providers who had training in end-of-life care had higher average levels of moral distress than those without this training (p = .005). CONCLUSIONS: Although there may be differences in perspectives and experiences, moral distress is a common experience for clinicians, regardless of profession. CLINICAL RELEVANCE: Moral distress is associated with burnout and intention to leave a position. By understanding its root causes, interventions can be tailored to minimize moral distress with the ultimate goal of enhancing patient care, staff satisfaction, and retention.

BACKGROUND: The National Cardiogenic Shock Initiative is a single-arm, prospective, multicenter study to assess outcomes associated with early mechanical circulatory support (MCS) in patients presenting with acute myocardial infarction and cardiogenic shock (AMICS) treated with percutaneous coronary intervention (PCI). METHODS: Between July 2016 and February 2019, 35 sites participated and enrolled into the study. All centers agreed to treat patients with AMICS using a standard protocol emphasizing invasive hemodynamic monitoring and rapid initiation of MCS. Inclusion and exclusion criteria mimicked those of the "SHOCK" trial with an additional exclusion criteria of intra-aortic balloon pump counter-pulsation prior to MCS. RESULTS: A total of 171 consecutive patients were enrolled. Patients had an average age of 63 years, 77% were male, and 68% were admitted with AMICS. About 83% of patients were on vasopressors or inotropes, 20% had a witnessed out of hospital cardiac arrest, 29% had in-hospital cardiac arrest, and 10% were under active cardiopulmonary resuscitation during MCS implantation. In accordance with the protocol, 74% of patients had MCS implanted prior to PCI. Right heart catheterization was performed in 92%. About 78% of patients presented with ST-elevation myocardial infarction with average door to support times of 85 ± 63 min and door to balloon times of 87 ± 58 min. Survival to discharge was 72%. Creatinine ≥2, lactate >4, cardiac power output (CPO) <0.6 W, and age ≥ 70 years were predictors of mortality. Lactate and CPO measurements at 12-24 hr reliably predicted overall mortality postindex procedure. CONCLUSION: In contemporary practice, use of a shock protocol emphasizing best practices is associated with improved outcomes.

In the adult brain, multiple cell types are known to produce factors that regulate blood-brain barrier (BBB) properties, including astrocytes. Yet several recent studies disputed a role for mature astrocytes at the BBB. To determine if astrocytes contribute a nonredundant and necessary function in maintaining the adult BBB, we used a mouse model of tamoxifen-inducible astrocyte ablation. In adult mice, tamoxifen induction caused sparse apoptotic astrocyte cell death within 2 hr. Indicative of BBB damage, leakage of the small molecule Cadaverine, and the large plasma protein fibrinogen into the brain parenchyma indicative of BBB damage was detected as early as astrocyte ablation was present. Vessels within and close to regions of astrocyte loss had lower expression of the tight junction protein zonula occludens-1 while endothelial glucose transporter 1 expression was undisturbed. Cadaverine leakage persisted for several weeks suggesting a lack of barrier repair. This is consistent with the finding that ablated astrocytes were not replaced. Adjacent astrocytes responded with partial nonproliferative astrogliosis, characterized by morphological changes and delayed phosphorylation of STAT3, which restricted dye leakage to the brain and vessel surface areas lacking coverage by astrocytes 1 month after ablation. In conclusion, astrocytes are necessary to maintain BBB integrity in the adult brain. BBB-regulating factors secreted by other cell types, such as pericytes, are not sufficient to compensate for astrocyte loss.

Abstract Rituximab, a chimeric antibody that targets CD20+ B cells, produces a 48% response rate in patients with refractory low-grade non-Hodgkin lymphoma. In this phase II trial, patients with low-grade non-Hodgkin lymphoma who had previously received no systemic therapy were treated with rituximab, 375 mg/m2, administered by IV infusion for 4 consecutive weeks. Patients with objective response or stable disease received repeat 4-week courses of rituximab at 6-month intervals. At the time of initial reevaluation at 6 weeks, 21 of 39 patients (54%) had objective response to treatment, and an additional 14 patients (36%) had stable disease or minor response. Response rates were similar in patients with follicular and small lymphocytic (CLL-type) lymphoma (52% versus 57%, respectively). At present, follow-up is short and only 13 patients have undergone a second course of rituximab treatment. However, 4 additional responses were documented either prior to the second course of rituximab (2 patients) or following the second course (2 patients) and 4 patients improved from partial to complete response. The current response rate is 64%, with 6 complete responses (15%). Treatment with rituximab was well tolerated, with only 1 patient experiencing grade 3/4 infusion-related toxicity. Rituximab is well tolerated and highly active in patients with low-grade non-Hodgkin lymphoma previously untreated with systemic therapy. Although further follow-up is required, the demonstration of minimal toxicity and considerable activity of this new biologic agent represents an important beginning of more specific, less toxic treatment for this important group of cancer patients.

OBJECTIVE: Open reduction and internal fixation of unstable posterior pelvic ring injury provides better bony stability and less long term morbidity than nonoperative treatment. However, open reduction and internal fixation of the posterior pelvis may involve substantial intraoperative blood loss, reported infection rates of 6 to 25%, and wound complications in 25%. Our hypothesis was that percutaneous cannulated iliosacral screws placed by fluoroscopic control would provide early, rapid, definitive stabilization with minimal blood loss, infection, and wound complications. DESIGN: A retrospective medical record and radiographic study. MATERIALS, METHODS, MEASUREMENTS AND MAIN RESULTS: Twenty consecutive patients with an unstable posterior pelvic ring injury treated by percutaneous fixation (41 screws) under fluoroscopic guidance were reviewed. Average patient age was 34 years, trauma score was 14.4 +/- 3.3, and Injury Severity Score was 22.9 +/- 10.6. Mechanisms were motor vehicle collisions (11), falls (3), crush injury (3), and pedestrian/auto (3). Pelvic injuries were classified as Tile B (5) or Tile C (15). Associated injuries were present in 80%. Seventy-five percent of patients underwent pelvic fixation less than 72 hours after injury with closed percutaneous screw placement achieved in 60%, assisted by open reduction in 25% or aided by anterior external fixation in 15%. Mean operative time was 52 minutes for patients requiring percutaneous screws only (7 of 20 patients, 35%), whereas average blood loss was 233 mL for all cases (including open anterior and posterior procedures). No loss of fixation or wound complications occurred during 9.6 months follow-up. CONCLUSIONS: Percutaneous iliosacral screw fixation for unstable posterior pelvic disruption provided early fixation with minimal operative time, minimal blood loss, and wound-related morbidity.

A modified low-dose paratracheal approach to stellate ganglion block at the C6 level prevents the possible complications of subarachnoid introduction of large quantities of local anesthetic, brachial plexus block, and toxic reaction to local anesthetics. It is a technically simple procedure with readily identifiable landmarks and can be performed on an outpatient basis with short recovery periods. Successful block can be readily evaluated. It is emphasized that a series of blocks is required to "disorganize" the reflex activity triggered in the internuncial pools of the spinal cord as well as in the sympathetic ganglia themselves.

Contrast induced nephropathy (CIN) is the third leading cause of hospital acquired renal failure and is associated with significant morbidity and mortality. Chronic kidney disease is the primary predisposing factor for CIN. As estimated glomerular filtration rate<60 ml/1.73 m2 represents significant renal dysfunction and defines patients at high risk. Modifiable risk factors for CIN include hydration status, the type and amount of contrast, use of concomitant nephrotoxic agents and recent contrast administration. The cornerstone of CIN prevention, in both the high and low risk patients, is adequate parenteral volume repletion. In the patient at increased risk for CIN it is often appropriate to withhold potentially nephrotoxic medications, and consider the use of n-acetylcysteine. In patients at increased risk for CIN the use of low or iso-osomolar contrast agents should be utilized and strategies employed to minimize contrast volume. In these patients serum creatinine should be obtained forty-eight hours post procedure and it is often appropriate to continue withholding medications such as metformin or non steroidal anti-inflammatories until renal function returns to normal.

BACKGROUND: Initial management of community-acquired pneumonia (CAP) has been a Centers for Medicare and Medicaid Services performance measure for a decade. We hypothesized that an intervention directed at management of CAP that assesses areas not covered by the performance measures-treatment duration and antimicrobial selection after additional microbiology data are available--would further improve CAP management. METHODS: We performed a single-center, prospective study to compare management of adult inpatients with presumed CAP before (from 1 January 2008 through 31 March 2008) and after (from 1 February 2010 through 10 May 2010) an intervention consisting of education and prospective feedback to teams regarding antibiotic choice and duration. The primary outcome measure was duration of antibiotic therapy in the 2 periods. RESULTS: There were 62 patients in the preintervention period and 65 patients in the intervention period. The duration of antibiotic therapy decreased from a median of 10 to 7 days (P < .001), with 148 fewer days of antibiotic therapy. The median lengths of stay were similar in the 2 groups (4 vs 5 days). A causative pathogen was identified less frequently during the intervention period (14% vs 34%); however, antibiotics were more frequently narrowed or modified on the basis of susceptibility results during the intervention period (67% vs 19%). Fewer patients received duplicate therapy within 24 hours in the intervention period (90% vs 55%). CONCLUSIONS: The duration of therapy for CAP was excessive at our institution and was decreased with a stewardship intervention. Confirmatory studies at other institutions are needed; efforts to assess and reduce duration of therapy for CAP should be strongly considered.

Invasive fungal infections (IFIs) are occurring with increasing incidence and are associated with significant morbidity and mortality. Understanding the relationship between the pharmacokinetic and pharmacodynamic properties of antifungals is essential to optimize the potential for favourable clinical and microbiological outcomes while minimizing risks of treatment-related toxicity. Antifungal serum concentrations may aid in the determination of appropriate dosing in select circumstances. The polyene and echinocandin classes of antifungals lack sufficient data to justify serum concentration monitoring in routine clinical practice. In contrast, serum concentration monitoring of flucytosine may help to reduce the risk of treatment-related haematological toxicity. Determination of itraconazole serum concentrations is advised in situations where the drug is used for prolonged periods to treat serious IFIs (such as invasive aspergillosis or histoplasmosis) because of variability in absorption following oral administration (most notable for the capsule formulation). The use of serum concentration monitoring during therapy with the extended-spectrum triazoles (i.e. voriconazole and posaconazole) is still evolving, due primarily to inter-patient variability in drug exposure combined with sparse data regarding relationships with efficacy (posaconazole) and both safety and efficacy (voriconazole).

Focal traumatic brain injury (TBI) induces astrogliosis, a process essential to protecting uninjured brain areas from secondary damage. However, astrogliosis can cause loss of astrocyte homeostatic functions and possibly contributes to comorbidities such as posttraumatic epilepsy (PTE). Scar-forming astrocytes seal focal injuries off from healthy brain tissue. It is these glial scars that are associated with epilepsy originating in the cerebral cortex and hippocampus. However, the vast majority of human TBIs also present with diffuse brain injury caused by acceleration-deceleration forces leading to tissue shearing. The resulting diffuse tissue damage may be intrinsically different from focal lesions that would trigger glial scar formation. Here, we used mice of both sexes in a model of repetitive mild/concussive closed-head TBI, which only induced diffuse injury, to test the hypothesis that astrocytes respond uniquely to diffuse TBI and that diffuse TBI is sufficient to cause PTE. Astrocytes did not form scars and classic astrogliosis characterized by upregulation of glial fibrillary acidic protein was limited. Surprisingly, an unrelated population of atypical reactive astrocytes was characterized by the lack of glial fibrillary acidic protein expression, rapid and sustained downregulation of homeostatic proteins and impaired astrocyte coupling. After a latency period, a subset of mice developed spontaneous recurrent seizures reminiscent of PTE in human TBI patients. Seizing mice had larger areas of atypical astrocytes compared with nonseizing mice, suggesting that these atypical astrocytes might contribute to epileptogenesis after diffuse TBI. SIGNIFICANCE STATEMENT Traumatic brain injury (TBI) is a leading cause of acquired epilepsies. Reactive astrocytes have long been associated with seizures and epilepsy in patients, particularly after focal/lesional brain injury. However, most TBIs also include nonfocal, diffuse injuries. Here, we showed that repetitive diffuse TBI is sufficient for the development of spontaneous recurrent seizures in a subset of mice. We identified an atypical response of astrocytes induced by diffuse TBI characterized by the rapid loss of homeostatic proteins and lack of astrocyte coupling while reactive astrocyte markers or glial scar formation was absent. Areas with atypical astrocytes were larger in animals that later developed seizures suggesting that this response may be one root cause of epileptogenesis after diffuse TBI.

Subclavian vein thrombosis is a relatively uncommon but potentially morbid disease entity. To determine the frequency, cause, and best mode of treatment of this problem, we performed a chart review of all patients with a diagnosis of subclavian vein thrombosis at two major metropolitan hospitals during a 6-year period. A total of 40 patients were identified with subclavian vein thrombosis, which represented 3.5% of all venous thromboses detected during the 6-year period. No side or sex predilection was noted and the majority of patients were outpatients. The cause was fairly evenly divided among intravenous catheters (32%), anatomic abnormalities (45%), and carcinoma with postoperative radiation (22.5%). Despite the increasing use of the subclavian veins for pacemaker leads, hyperalimentation, and permanent intravenous access for chemotherapy, there has not been an increase in diagnosed subclavian vein thrombosis. Anatomic abnormalities with compression of the vein respond well to either heparinization or lytic therapy but require surgery if the venous abnormality persists. Treatment consisted of lytic therapy in 20%, heparinization in 55%, and elevation with removal of the central line in 25% of patients. All patients responded well to treatment, with a decrease in swelling and symptoms; no patient progressed to venous gangrene and only one (2.5%) had a documented pulmonary embolus. Medical treatment provides excellent long-term benefit in most cases unless complicated by an anatomic abnormality.

Political ideologies summarize dimensions of life that define how a person organizes their public and private behavior, including their attitudes associated with sex, family, education, and personal autonomy [1Jost J.T. Federico C.M. Napier J.L. Political ideology: its structure, functions, and elective affinities.Annu. Rev. Psychol. 2009; 60: 307-337Crossref PubMed Scopus (1055) Google Scholar, 2Haidt J. The Righteous Mind: Why Good People Are Divided by Religion and Politics. Pantheon, New York2012Google Scholar]. Despite the abstract nature of such sensibilities, fundamental features of political ideology have been found to be deeply connected to basic biological mechanisms [3Fowler J.H. Baker L.A. Dawes C.T. Genetic variation in political participation.Am. Polit. Sci. Rev. 2008; 102: 233-248Crossref Scopus (256) Google Scholar, 4Alford J.R. Funk C.L. Hibbing J.R. Are political orientations genetically transmitted?.Am. Polit. Sci. Rev. 2005; 99: 153-167Crossref Scopus (590) Google Scholar, 5Hatemi P.K. Gillespie N.A. Eaves L.J. Maher B.S. Webb B.T. Heath A.C. Medland S.E. Smyth D.C. Beeby H.N. Gordon S.D. et al.A genome-wide analysis of liberal and conservative political attitudes.J. Polit. 2011; 73: 271-285Crossref Scopus (86) Google Scholar, 6Settle J.E. Dawes C.T. Fowler J.H. The heritability of partisan attachment.Polit. Res. Q. 2009; 62: 601-613Crossref Scopus (103) Google Scholar, 7Kanai R. Feilden T. Firth C. Rees G. Political orientations are correlated with brain structure in young adults.Curr. Biol. 2011; 21: 677-680Abstract Full Text Full Text PDF PubMed Scopus (275) Google Scholar] that may serve to defend against environmental challenges like contamination and physical threat [8Amodio D.M. Jost J.T. Master S.L. Yee C.M. Neurocognitive correlates of liberalism and conservatism.Nat. Neurosci. 2007; 10: 1246-1247Crossref PubMed Scopus (379) Google Scholar, 9Oxley D.R. Smith K.B. Alford J.R. Hibbing M.V. Miller J.L. Scalora M. Hatemi P.K. Hibbing J.R. Political attitudes vary with physiological traits.Science. 2008; 321: 1667-1670Crossref PubMed Scopus (374) Google Scholar, 10Dodd M.D. Balzer A. Jacobs C.M. Gruszczynski M.W. Smith K.B. Hibbing J.R. The political left rolls with the good and the political right confronts the bad: connecting physiology and cognition to preferences.Philos. Trans. R. Soc. Lond. B Biol. Sci. 2012; 367: 640-649Crossref PubMed Scopus (137) Google Scholar, 11Smith K.B. Oxley D. Hibbing M.V. Alford J.R. Hibbing J.R. Disgust sensitivity and the neurophysiology of left-right political orientations.PLoS ONE. 2011; 6: e25552Crossref PubMed Scopus (167) Google Scholar, 12Schaller M. Park J.H. The behavioral immune system (and why it matters).Curr. Dir. Psychol. Sci. 2011; 20: 99-103Crossref Scopus (608) Google Scholar]. These results invite the provocative claim that neural responses to nonpolitical stimuli (like contaminated food or physical threats) should be highly predictive of abstract political opinions (like attitudes toward gun control and abortion) [13Hibbing J.R. Smith K.B. Alford J.R. Differences in negativity bias underlie variations in political ideology.Behav. Brain Sci. 2014; 37: 297-307Crossref PubMed Scopus (343) Google Scholar]. We applied a machine-learning method to fMRI data to test the hypotheses that brain responses to emotionally evocative images predict individual scores on a standard political ideology assay. Disgusting images, especially those related to animal-reminder disgust (e.g., mutilated body), generate neural responses that are highly predictive of political orientation even though these neural predictors do not agree with participants’ conscious rating of the stimuli. Images from other affective categories do not support such predictions. Remarkably, brain responses to a single disgusting stimulus were sufficient to make accurate predictions about an individual subject’s political ideology. These results provide strong support for the idea that fundamental neural processing differences that emerge under the challenge of emotionally evocative stimuli may serve to structure political beliefs in ways formerly unappreciated.

Abstract Background Gastric variceal bleeding carries significant mortality in the setting of portal hypertension. Among the endoscopic treatment options, endoscopic ultrasound (EUS)-guided glue and/or coil injection is a novel approach, but its role in the treatment of gastric varices is not established due to a lack of robust data. Methods We conducted a comprehensive search of several databases (inception to June 2019) to identify studies evaluating EUS in the treatment of gastric varices. Our primary goals were to estimate the pooled rates of treatment efficacy, obliteration and recurrence of gastric varices, early and late rebleeding, and adverse events with EUS-guided therapy in gastric varices. We also searched for studies that evaluated direct endoscopic glue (END-glue) injection for treatment of gastric varices, and used the pooled rates as comparators. Results 23 studies (851 patients) evaluating EUS-guided therapy were included. The pooled treatment efficacy was 93.7 % (95 % confidence interval [CI] 89.5 – 96.3, I 2 = 53.7), gastric varices obliteration was 84.4 % (95 %CI 74.8 – 90.9, I 2 = 77), gastric varices recurrence was 9.1 % (95 %CI 5.2 – 15.7, I 2 = 32), early rebleeding was 7.0 % (95 %CI 4.6 – 10.7, I 2 = 0), and late rebleeding was 11.6 % (95 %CI 8.8 – 15.1, I 2 = 22). The rates were comparable to END-glue therapy (28 studies, 3467 patients) except for obliteration, which was significantly better with EUS-guided therapy. On subgroup analysis, EUS-coil/glue combination showed superior outcomes. Conclusions EUS-guided therapy demonstrated clinical efficacy for treatment of gastric varices in terms of obliteration, recurrence, and long-term rebleeding, and may be superior to END-glue.

Abstract Background Endoscopic transpapillary gallbladder drainage (ETGBD) and endoscopic ultrasound-guided gallbladder drainage (EUSGBD) are alternatives to percutaneous gallbladder drainage (PCGBD) for patients with acute cholecystitis who are unfit for surgery. Data comparing these modalities are limited and have reported conflicting results. Methods We searched multiple databases from inception to May 2019 to identify studies that reported on ETGBD, EUSGBD, and PCGBD in the management of acute cholecystitis in patients with a high surgical risk. Aims were to compare the pooled rates of technical success, clinical success, adverse events, and disease recurrence. Results 1223 patients (22 studies), 557 patients (14 studies), and 13 351 patients (46 studies) were treated by ETGBD, EUSGBD, and PCGBD, respectively. The pooled technical and clinical successes were: ETGBD 83 % (95 % confidence interval [CI] 80.1 – 85.5, I 2 = 29) and 88.1 % (95 %CI 83.6 – 91.4, I 2 = 50), respectively; EUSGBD 95.3 % (95 %CI 92.8 – 96.9, I 2 = 0) and 96.7 % (95 %CI 94.0 – 98.2, I 2 = 0), respectively; and PCGBD 98.7 % (95 %CI 98.0 – 99.1, I 2 = 0) and 89.3 % (95 %CI 86.6 – 91.5, I 2 = 84), respectively. Clinical success with EUSGBD was significantly superior to the other approaches. All complications were comparable between the groups. Pancreatitis occurred with ETGBD in 5.1 % (95 %CI 3.5 – 7.3), whereas bleeding and perforation occurred with EUSGBD in 4.3 % (95 %CI 2.7 – 6.8) and 3.7 % (95 %CI 2.3 – 6.0), respectively. Stent migration occurred with PCGBD in 7.4 % (95 %CI 5.5 – 10.0). Conclusion EUSGBD demonstrated better clinical success than ETGBD and PCGBD in the management of acute cholecystitis patients at high surgical risk.

BACKGROUND AND PURPOSE: On the basis of phase II trials, we considered that transcranial laser therapy could have neuroprotective effects in patients with acute ischemic stroke. METHODS: We studied transcranial laser therapy in a double-blind, sham-controlled randomized clinical trial intended to enroll 1000 patients with acute ischemic stroke treated ≤24 hours after stroke onset and who did not undergo thrombolytic therapy. The primary efficacy measure was the 90-day functional outcome as assessed by the modified Rankin Scale, with hierarchical Bayesian analysis incorporating relevant previous data. Interim analyses were planned after 300 and 600 patients included. RESULTS: The study was terminated on recommendation by the Data Monitoring Committee after a futility analysis of 566 completed patients found no difference in the primary end point (transcranial laser therapy 140/282 [49.6%] versus sham 140/284 [49.3%] for good functional outcome; modified Rankin Scale, 0-2). The results remained stable after inclusion of all 630 randomized patients (adjusted odds ratio, 1.024; 95% confidence interval, 0.705-1.488). CONCLUSIONS: Once the results of the interim futility analysis became available, all study support was immediately withdrawn by the capital firms behind PhotoThera, and the company was dissolved. Proper termination of the trial was difficult but was finally achieved through special efforts by former employees of PhotoThera, the CRO Parexel and members of the steering and the safety committees. We conclude that transcranial laser therapy does not have a measurable neuroprotective effect in patients with acute ischemic stroke when applied within 24 hours after stroke onset. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01120301.

Interpersonal problems are a core symptom of borderline personality disorder (BPD). This study investigated the relationship between emotion dysregulation, impulsiveness, and impaired mentalizing in the context of predicting interpersonal problems in BPD. A total of 210 patients with BPD completed the Difficulties in Emotion Regulation Scale (DERS), Barratt Impulsiveness Scale (BIS-11), Reflective Functioning Questionnaire (RFQ), and Inventory of Interpersonal Problems (IIP-32). The authors conducted three path models, with either mentalizing, emotion regulation, or impulsiveness as the exogenous variable. Emotion dysregulation and attentional impulsiveness predicted interpersonal problems directly, whereas hypomentalizing predicted interpersonal problems only indirectly throughout emotion dysregulation and attentional impulsiveness. The results suggest that these domains contribute significantly to interpersonal problems in BPD. Moreover, hypomentalizing might affect on interpersonal problems via its effect on impulsiveness and emotion regulation. The authors argue that focusing on emotion regulation and mentalizing in BPD treatments might have interlinked beneficial effects on interpersonal problems.

Metabolomics is the latest 'omics' technology and systems biology science that allows for comprehensive profiling of small-molecule metabolites in biological systems at a specific time and condition. Metabolites are cellular intermediate products of metabolic reactions, which reflect the ultimate response to genomic, transcriptomic, proteomic, or environmental changes in a biological system. Aging is a complex biological process that is characterized by a gradual and progressive decline in molecular, cellular, tissue, organ, and organismal functions, and it is influenced by a combination of genetic, environmental, diet, and lifestyle factors. The precise biological mechanisms of aging remain unknown. Metabolomics has emerged as a powerful tool to characterize the organism phenotypes, identify altered metabolites, pathways, novel biomarkers in aging and disease, and offers wide clinical applications. Here, I will provide a comprehensive overview of our current knowledge on metabolomics led studies in aging with particular emphasis on studies leading to biomarker discovery. Based on the data obtained from model organisms and humans, it is evident that metabolites associated with amino acids, lipids, carbohydrate, and redox metabolism may serve as biomarkers of aging and/or longevity. Current challenges and key questions that should be addressed in the future to advance our understanding of the biological mechanisms of aging are discussed.

BACKGROUND: The impact of diagnostic delay in inflammatory bowel disease, including Crohn's disease (CD) and ulcerative colitis (UC), on disease course remains uncertain. This study examines factors that may influence time to diagnosis and disease outcomes in a U.S. patient cohort. METHODS: We retrospectively collected data on patient characteristics, time to diagnosis, disease phenotype, and complications in 177 patients with inflammatory bowel disease (110 CD and 67 UC) diagnosed at our institution from 2008 to 2015. Factors potentially affecting time to diagnosis were analyzed. Association between disease complications (perianal disease, intestinal strictures, surgery, fistula, abscess, and perforation) and time to diagnosis was tested by multivariable analysis. RESULTS: The median time to diagnosis was longer for patients with CD compared with patients with UC (median 9.5 versus 3.1 months; P < 0.001). The median time from symptom onset to initial physician visit was similar for patients with CD and patients with UC (1 month). However, the median time from symptom onset to specialist evaluation was longer for patients with CD compared with patients with UC: 7 months (interquartile range: 3-23) versus 3 months (interquartile range: 1-8), respectively (P < 0.001). In CD, ileal disease and hematochezia were positively and negatively correlated, respectively, with longer time to diagnosis (P < 0.05). Compared with patients with time to diagnosis ≤4 months, patients with time >26 months had increased overall complications (odds ratio, 8.22; P = 0.007) and intestinal strictures (odds ratio, 8.96; P = 0.012) at time of diagnosis. Such correlation persisted at follow-up. CONCLUSIONS: Time to diagnosis was long in CD. Physician-related delay in diagnosing CD was associated with increased overall complications and intestinal strictures (See Video Abstract, Supplemental Digital Content 1, http://links.lww.com/IBD/B646).