The authors reply

No abstract available

http://ift.tt/2sbL7Ac

Sepsis-Associated 30-Day Risk-Standardized Readmissions: Analysis of a Nationwide Medicare Sample*

Objectives: To determine national readmission rates among sepsis survivors, variations in rates between hospitals, and determine whether measures of quality correlate with performance on sepsis readmissions. Design: Cross-sectional study of sepsis readmissions between 2008 and 2011 in the Medicare fee-for-service database. Setting: Acute care, Medicare participating hospitals from 2008 to 2011. Patients: Septic patients as identified by International Classification of Diseases, Ninth Revision codes using the Angus method. Interventions: None. Measurements and Main Results: We generated hospital-level, risk-standardized, 30-day readmission rates among survivors of sepsis and compared rates across region, ownership, teaching status, sepsis volume, hospital size, and proportion of underserved patients. We examined the relationship between risk-standardized readmission rates and hospital-level composite measures of quality and mortality. From 633,407 hospitalizations among 3,315 hospitals from 2008 to 2011, median risk-standardized readmission rates was 28.7% (interquartile range, 26.1–31.9). There were differences in risk-standardized readmission rates by region (Northeast, 30.4%; South, 29.6%; Midwest, 28.8%; and West, 27.7%; p

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Pheochromocytoma Crisis in the ICU: A French Multicenter Cohort Study With Emphasis on Rescue Extracorporeal Membrane Oxygenation

Objectives: To describe the characteristics, management, and outcome of patients admitted to ICUs for pheochromocytoma crisis. Design: A 16-year multicenter retrospective study. Setting: Fifteen university and nonuniversity ICUs in France. Patients: Patients admitted in ICU for pheochromocytoma crisis. Interventions: None. Measurement and Main Results: We included 34 patients with a median age of 46 years (40–54 yr); 65% were males. At admission, the median Sequential Organ Failure Assessment score was 8 (4–12) and median Simplified Acute Physiology Score II 49.5 (27–70). The left ventricular ejection fraction was consistently decreased with a median value of 30% (15–40%). Mechanical ventilation was required in 23 patients, mainly because of congestive heart failure. Vasoactive drugs were used in 23 patients (68%) and renal replacement therapy in eight patients (24%). Extracorporeal membrane oxygenation was used as a rescue therapy in 14 patients (41%). Pheochromocytoma was diagnosed by CT in 33 of 34 patients. When assayed, urinary metanephrine and catecholamine levels were consistently elevated. Five patients underwent urgent surgery, including two during extracorporeal membrane oxygenation. Overall ICU mortality was 24% (8/34), and overall 90-day mortality was 27% (9/34). Crude 90-day mortality was not significantly different between patients managed with versus without extracorporeal membrane oxygenation (22% vs 30%) (p = 0.7) despite higher severity scores at admission in the extracorporeal membrane oxygenation group. Conclusions: Mortality is high in pheochromocytoma crisis. Routinely considering this diagnosis and performing abdominal CT in patients with unexplained cardiogenic shock may allow an earlier diagnosis. Extracorporeal membrane oxygenation and adrenalectomy should be considered as a therapeutic in most severe cases.

http://ift.tt/2sbvb0G

Simulation of a Novel Schedule for Intensivist Staffing to Improve Continuity of Patient Care and Reduce Physician Burnout

Objective: Despite widespread adoption of in-house call for ICU attendings, there is a paucity of research on optimal scheduling of intensivists to provide continuous on-site coverage. Overnight call duties have traditionally been added onto 7 days of continuous daytime clinical service. We designed an alternative ICU staffing model to increase continuity of attending physician care for patients while also decreasing interruptions to attendings' nonclinical weeks. Design: Computer-based simulation of a 1-year schedule. Setting: A simulated ICU divided into two daytime teams each covered by a different attending and both covered by one overnight on-call attending. Subjects: Simulated patients were randomly admitted on different service days to assess continuity of care. Interventions: A "shared service schedule" was compared to a standard "7 days on schedule." For the 7 days on schedule, an attending covered a team for 7 consecutive days and off-service attendings cross-covered each night. For the shared schedule, four attendings shared the majority of daytime and nighttime service for two teams over 2 weeks, with recovery periods built into the scheduled service time. Measurements and Main Results: Continuity of care as measured by the Continuity of Attending Physician Index increased by 9% with the shared schedule. Annually, the shared service schedule was predicted to increase free weekends by 3.4 full weekends and 1.3 weekends with either Saturday or Sunday off. Full weeks without clinical obligations increased by 4 weeks. Mean time between clinical obligations increased by 5.8 days. Conclusions: A shared service schedule is predicted to improve continuity of care while increasing free weekends and continuity of uninterrupted nonclinical weeks for attendings. Computer-based simulation allows assessment of benefits and tradeoffs of the alternative schedule without disturbing existing clinical systems.

http://ift.tt/2tcPOId

Accuracy of Zero-Heat-Flux Cutaneous Temperature in Intensive Care Adults

Objectives: To compare accuracy of a continuous noninvasive cutaneous temperature using zero-heat-flux method to esophageal temperature and arterial temperature. Design: Prospective study. Setting: ICU and NeuroICU, University Hospital. Patients: Fifty-two ICU patients over a 4-month period who required continuous temperature monitoring were included in the study, after informed consent. Interventions: All patients had esophageal temperature probe and a noninvasive cutaneous device to monitor their core temperature continuously. In seven patients who required cardiac output monitoring, continuous iliac arterial temperature was collected. Simultaneous core temperatures were recorded from 1 to 5 days. Comparison to the esophageal temperature, considered as the reference in this study, used the Bland and Altman method with adjustment for multiple measurements per patient. Measurements and Main Results: The esophageal temperature ranged from 33°C to 39.7°C, 61,298 pairs of temperature using zero-heat-flux and esophageal temperature were collected and 1,850 triple of temperature using zero-heat-flux, esophageal temperature, and arterial temperature. Bias and limits of agreement for temperature using zero-heat-flux were 0.19°C ± 0.53°C compared with esophageal temperature with an absolute difference of temperature pairs equal to or lower than 0.5°C of 92.6% (95% CI, 91.9–93.4%) of cases and equal to or lower than 1°C for 99.9% (95% CI, 99.7–100.0%) of cases. Compared with arterial temperature, bias and limits of agreement were –0.00°C ± 0.36°C with an absolute difference of temperature pairs equal to or lower than 0.5°C of 99.8% (95% CI, 95.3–100%) of cases. All absolute difference of temperature pairs between temperature using zero-heat-flux and arterial temperature and between arterial temperature and esophageal temperature were equal to or lower than 1°C. No local or systemic serious complication was observed. Conclusions: These results suggest a comparable reliability of the cutaneous sensor using the zero-heat-flux method compared with esophageal or iliac arterial temperatures measurements.

http://ift.tt/2sbL7jG

Neuron-Specific Enolase Predicts Poor Outcome After Cardiac Arrest and Targeted Temperature Management: A Multicenter Study on 1,053 Patients

Objective: Outcome prediction after cardiac arrest is important to decide on continuation or withdrawal of intensive care. Neuron-specific enolase is an easily available, observer-independent prognostic biomarker. Recent studies have yielded conflicting results on its prognostic value after targeted temperature management. Design, Setting, and Patients: We analyzed neuron-specific enolase serum concentrations 3 days after nontraumatic in-hospital cardiac arrest and out-of-hospital cardiac arrest and outcome of patients from five hospitals in Germany, Austria, and Italy. Patients were treated at 33°C for 24 hours. Cerebral Performance Category was evaluated upon ICU discharge. We performed case reviews of good outcome patients with neuron-specific enolase greater than 90 μg/L and poor outcome patients with neuron-specific enolase less than or equal to 17 μg/L (upper limit of normal). Measurements and Main Results: A neuron-specific enolase serum concentration greater than 90 μg/L predicted Cerebral Performance Category 4–5 with a positive predictive value of 99%, false positive rate of 0.5%, and a sensitivity of 48%. All three patients with neuron-specific enolase greater than 90 μg/L and Cerebral Performance Category 1–2 had confounders for neuron-specific enolase elevation. An neuron-specific enolase serum concentration less than or equal to 17 μg/L excluded Cerebral Performance Category 4–5 with a negative predictive value of 92%. The majority of 14 patients with neuron-specific enolase less than or equal to 17 μg/L who died had a cause of death other than hypoxic-ischemic encephalopathy. Specificity and sensitivity for prediction of poor outcome were independent of age, sex, and initial rhythm but higher for out-of-hospital cardiac arrest than for in-hospital cardiac arrest patients. Conclusion: High neuron-specific enolase serum concentrations reliably predicted poor outcome at ICU discharge. Prediction accuracy differed and was better for out-of-hospital cardiac arrest than for in-hospital cardiac arrest patients. Our "in-the-field" data indicate 90 μg/L as a threshold associated with almost no false positives at acceptable sensitivity. Confounders of neuron-specific enolase elevation should be actively considered: neuron-specific enolase–producing tumors, acute brain diseases, and hemolysis. We strongly recommend routine hemolysis quantification. Neuron-specific enolase serum concentrations less than or equal to 17 μg/L argue against hypoxic-ischemic encephalopathy incompatible with reawakening.

http://ift.tt/2tcFosf

The authors reply

No abstract available

http://ift.tt/2rGhJOE

Pilot Feasibility Study of Therapeutic Hypothermia for Moderate to Severe Acute Respiratory Distress Syndrome*

Objectives: Prior studies suggest hypothermia may be beneficial in acute respiratory distress syndrome, but cooling causes shivering and increases metabolism. The objective of this study was to assess the feasibility of performing a randomized clinical trial of hypothermia in patients with acute respiratory distress syndrome receiving treatment with neuromuscular blockade because they cannot shiver. Design: Retrospective study and pilot, prospective, open-label, feasibility study. Setting: Medical ICU. Patients: Retrospective review of 58 patients with acute respiratory distress syndrome based on Berlin criteria and PaO2/FIO2 less than 150 who received neuromuscular blockade. Prospective hypothermia treatment in eight acute respiratory distress syndrome patients with PaO2/FIO2 less than 150 receiving neuromuscular blockade. Intervention: Cooling to 34–36°C for 48 hours. Measurements and Main Results: Core temperature, hemodynamics, serum glucose and electrolytes, and P/F were sequentially measured, and medians (interquartile ranges) presented, 28-day ventilator-free days, and hospital mortality were calculated in historical controls and eight cooled patients. Average patient core temperature was 36.7°C (36–37.3°C), and fever occurred during neuromuscular blockade in 30 of 58 retrospective patients. In the prospectively cooled patients, core temperature reached target range less than or equal to 4 hours of initiating cooling, remained less than 36°C for 92% of the 48 hours cooling period without adverse events, and was lower than the controls (34.35°C [34–34.8°C]; p

http://ift.tt/2tcI3lH

The author replies

No abstract available

http://ift.tt/2sbqwf6

A Contemporary Assessment of Acute Mechanical Ventilation in Beijing: Description, Costs, and Outcomes

Objective: To evaluate the contemporary practice, outcomes, and costs related to mechanical ventilation among ICUs in China. Design: A prospective observational cohort study. Setting: Fourteen ICUs among 13 hospitals in Beijing, China. Patients: Seven hundred ninety-three patients who received at least 24 hours of mechanical ventilation within the first 48 hours of ICU stay. Intervention: None. Measurements and results: The mean age was 64 years. Sixty-three percent were male. New acute respiratory failure accounted for 85.5% of mechanical ventilation cases. Only 4.7% of the patients received mechanical ventilation for acute exacerbation of chronic obstructive pulmonary disease. The most widely used ventilation mode was the combination of synchronized intermittent mandatory ventilation and pressure support (43.6%). Use of lung-protective ventilation is widespread with tidal volumes of 7.1 mL/kg (2.1 mL/kg). The ICU/hospital mortality was 27.6%/29.3%, respectively (8.5%/9.7% for surgical patients and 41.3%/43.2% for medical patients, respectively). The mean level of ICU/hospital cost per patient was $15,271 (18,940)/$22,946 (25,575), respectively. The mean daily ICU cost per patient was $1,212. Conclusion: For the first time, we obtained a preliminary epidemiology data of mechanical ventilation in Beijing, China, through the study. Compared with the other nations, our patients are older, predominantly male, and treated according to prevailing international guidelines yet at a relatively high cost and high mortality. The expanding elderly population predicts increase demand for mechanical ventilation that must be met by continuous improvement in quality and efficiency of critical care services.

http://ift.tt/2tcILza

Urgent Chemotherapy for Life-Threatening Complications Related to Solid Neoplasms

Objectives: Solid neoplasms can be directly responsible for organ failures at the time of diagnosis or relapse. The management of such specific complications relies on urgent chemotherapy and eventual instrumental or surgical procedures, combined with advanced life support. We conducted a multicenter study to address the prognosis of this condition. Design: A multicenter retrospective (2001–2015) chart review. Setting: Medical and respiratory ICUs. Patients: Adult patients who received urgent chemotherapy in the ICU for organ failure related to solid neoplasms were included. The modalities of chemotherapy, requirements of adjuvant instrumental or surgical procedures, and organ supports were collected. Endpoints were short- and long-term survival rates. Interventions: None. Measurements and Main Results: One hundred thirty-six patients were included. Lung cancer was the most common malignancy distributed into small cell lung cancer (n = 57) and non-small cell lung cancer (n = 33). The main reason for ICU admission was acute respiratory failure in 111 patients (81.6%), of whom 89 required invasive mechanical ventilation. Compression and tissue infiltration by tumor cells were the leading mechanisms resulting in organ involvement in 78 (57.4%) and 47 (34.6%) patients. The overall in-ICU, in-hospital, 6-month, and 1-year mortality rates were 37%, 58%, 74%, and 88%, respectively. Small cell lung cancer was identified as an independent predictor of hospital survival. However, this gain in survival was not sustained since the 1-year survival rates of small cell lung cancer, non-small cell lung cancer, and non-lung cancer patients all dropped below 20%. Conclusions: Urgent chemotherapy along with aggressive management of organ failures in the ICU can be lifesaving in very selected cancer patients, most especially with small cell lung cancer, although the long-term survival is hardly sustainable.

http://ift.tt/2sby3uy

Population-Based Epidemiology of Sepsis in a Subdistrict of Beijing

Objective: Information about the epidemiology of sepsis in community residents in China remains scarce and incomplete. The purpose of this study was to describe the occurrence rate and outcome of sepsis in Yuetan Subdistrict of Beijing and to estimate the occurrence rate of sepsis in China. Design: Retrospective cohort study. Setting: All public hospitals serving residents in Yuetan Subdistrict, Beijing. Patients: All patients (n = 1,716) meeting criteria for sepsis based on American College of Chest Physicians/Society of Critical Care Medicine consensus definition. Interventions: None. Measurement and Main Results: We screened all adult residents in Yuetan Subdistrict who were hospitalized from July 1, 2012, to June 30, 2014, and reviewed medical records. Patients with sepsis were included in the analysis. We enrolled 1,716 patients with sepsis out of 21,191 hospitalized adults screened, among whom severe sepsis developed in 256 patients, and septic shock developed in 233 patients. The crude annual occurrence rates of sepsis, severe sepsis, and septic shock in Yuetan Subdistrict were 667, 103, and 91 cases per 100,000 population, corresponding to standardized occurrence rates of 461, 68, and 52 cases per 100,000 population per year, respectively. Both occurrence rate and mortality increased significantly with age, although males had higher age-adjusted occurrence rate and mortality. The occurrence rate of sepsis also exhibited seasonal variation, peaking in winter season. The overall hospital mortality rate of sepsis was 20.6%, yielding a standardized mortality rate of 79 cases per 100,000 population per year. Conclusions: Sepsis is a common and frequently fatal syndrome in Yuetan Subdistrict, Beijing. The occurrence rate and mortality of sepsis are significantly higher in males and elderly people.

http://ift.tt/2tcHEzL

Electroencephalography Predicts Poor and Good Outcomes After Cardiac Arrest: A Two-Center Study*

Objective: The prognostic role of electroencephalography during and after targeted temperature management in postcardiac arrest patients, relatively to other predictors, is incompletely known. We assessed performances of electroencephalography during and after targeted temperature management toward good and poor outcomes, along with other recognized predictors. Design: Cohort study (April 2009 to March 2016). Setting: Two academic hospitals (Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; Mayo Clinic, Rochester, MN). Patients: Consecutive comatose adults admitted after cardiac arrest, identified through prospective registries. Interventions: All patients were managed with targeted temperature management, receiving prespecified standardized clinical, neurophysiologic (particularly, electroencephalography during and after targeted temperature management), and biochemical evaluations. Measurements and Main Results: We assessed electroencephalography variables (reactivity, continuity, epileptiform features, and prespecified "benign" or "highly malignant" patterns based on the American Clinical Neurophysiology Society nomenclature) and other clinical, neurophysiologic (somatosensory-evoked potential), and biochemical prognosticators. Good outcome (Cerebral Performance Categories 1 and 2) and mortality predictions at 3 months were calculated. Among 357 patients, early electroencephalography reactivity and continuity and flexor or better motor reaction had greater than 70% positive predictive value for good outcome; reactivity (80.4%; 95% CI, 75.9–84.4%) and motor response (80.1%; 95% CI, 75.6–84.1%) had highest accuracy. Early benign electroencephalography heralded good outcome in 86.2% (95% CI, 79.8–91.1%). False positive rates for mortality were less than 5% for epileptiform or nonreactive early electroencephalography, nonreactive late electroencephalography, absent somatosensory-evoked potential, absent pupillary or corneal reflexes, presence of myoclonus, and neuron-specific enolase greater than 75 µg/L; accuracy was highest for early electroencephalography reactivity (86.6%; 95% CI, 82.6–90.0). Early highly malignant electroencephalography had an false positive rate of 1.5% with accuracy of 85.7% (95% CI, 81.7–89.2%). Conclusions: This study provides class III evidence that electroencephalography reactivity predicts both poor and good outcomes, and motor reaction good outcome after cardiac arrest. Electroencephalography reactivity seems to be the best discriminator between good and poor outcomes. Standardized electroencephalography interpretation seems to predict both conditions during and after targeted temperature management.

http://ift.tt/2sbvAAl

Resuscitation With Balanced Fluids Is Associated With Improved Survival in Pediatric Severe Sepsis*

Objective: To evaluate outcomes in patients receiving balanced fluids for resuscitation in pediatric severe sepsis. Design: Observational cohort review of prospectively collected data from a large administrative database. Setting: PICUs from 43 children's hospitals. Patients: PICU patients diagnosed with severe sepsis. Interventions: None. Measurements and Main Results: We reviewed data from the Pediatric Health Information System database from 2004 to 2012. Children with pediatric severe sepsis receiving balanced fluids for resuscitation in the first 24 and 72 hours of treatment were compared to those receiving unbalanced fluids. Thirty-six thousand nine hundred eight patients met entry criteria for analysis. Two thousand three hundred ninety-eight patients received exclusively balanced fluids at 24 hours and 1,641 at 72 hours. After propensity matching, the 72-hour balanced fluids group had lower mortality (12.5% vs 15.9%; p = 0.007; odds ratio, 0.76; 95% CI, 0.62–0.93), lower prevalence of acute kidney injury (16.0% vs 19.2%; p = 0.028; odds ratio, 0.82; 95% CI, 0.68–0.98), and fewer vasoactive infusion days (3.0 vs 3.3 d; p

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MicroRNA-21 Is Required for Local and Remote Ischemic Preconditioning in Multiple Organ Protection Against Sepsis*

Objective: Sepsis, triggered by microbial infection, is a common and life-threatening systemic illness, often leads to impaired function of vital organs. Ischemic preconditioning induced by transient brief episodes of ischemia is a powerful innate mechanism of organ protection. We have reported that a 15-minute renal ischemic preconditioning substantially attenuated subsequent renal ischemia-reperfusion injury. Here, we investigate whether a brief ischemia and reperfusion in kidney can provide protection at local and remote sites against sepsis-induced organ injury, and whether this protection is microRNA-21 dependent. Design: Laboratory study. Setting: University laboratory. Subjects: Mouse renal tubular epithelial cells, C57BL/6 J wildtype (Animal Center of Fudan University, Shanghai, China) and microRNA-21–/– mice (B6.129-Mir21atm1Smoc, Shanghai Biomodel Organism Science & Technology Development Co. Shanghai, China). Interventions: Mouse renal tubular epithelial cells were treated with hypoxia (2% oxygen). Renal ischemic preconditioning was induced by bilateral renal pedicle clamping for 15 minutes, and sepsis was induced by a single intraperitoneal injection of lipopolysaccharide at a dose of 20 mg/kg or cecal ligation and puncture in mice. Measurements and Main Results: Mice treated with renal ischemic preconditioning were protected from endotoxemia or polymicrobial sepsis-induced multiple organ injury, including kidneys, heart, liver, and lungs. Renal ischemic preconditioning induced activation of hypoxia-inducible factor-1α in kidneys, which up-regulated microRNA-21 at transcriptional level, subsequently, leading to increased expression of microRNA-21 in serum exosomes and remote organs, resulting in decreased apoptosis and reduced proinflammatory cytokines production in these organs. In vivo knockdown of microRNA-21 or genetic deletion of microRNA-21 abrogated the organoprotective effects conferred by renal ischemic preconditioning. Mechanistically, we discovered that knockdown of microRNA-21 increased programmed cell death protein 4 expression and nuclear factor-kappa B activity, decreased expression of anti-apoptotic B-cell lymphoma-2. Conclusion: MicroRNA-21 is required for local and remote ischemic preconditioning in multiple organ protection against sepsis, and up-regulation of miR-21 may be a potential therapy for sepsis.

http://ift.tt/2sbukx5

Distribution-Weighted Cost-Effectiveness Analysis Using Lifetime Health Loss

Abstract

Background

It is widely acknowledged that concerns for the worse off need to be integrated with the concern for cost effectiveness in priority setting, and several countries are seeking to do so. In Norway, a comprehensive framework for priority setting was recently proposed to specify the worse off in terms of lifetime loss of quality-adjusted life-years (QALYs). However, few studies have shown how to calculate such health losses, how to integrate health loss into cost-effectiveness analyses (CEAs) and how such integration impacts the incremental cost-effectiveness ratios (ICERs). The aim of this study was to do so.

Methods

The proposed framework was applied to data from 15 recent economic evaluations of drugs. Available data were used to calculate the lifetime health loss of the target groups, and the proposed marginal weighting function was employed to adjust standard ICERs according to the size of this loss. Standard and weighted ICERs were compared to a threshold of US$35,000 per QALY gained.

Results

Lifetime health loss can be calculated with the use of available data and integrated by a marginal weighting function with CEAs. Such integration affected standard ICERs to a varying degree and changed the number of interventions considered cost effective from three to eight.

Conclusion

Calculation of lifetime health loss and its integration with CEA is feasible and can influence the reimbursement and ranking of interventions. To facilitate regular integration, guidelines for economic evaluations could require (i) adjustment according to distributional concerns and (ii) that data on health loss are extracted directly from the models and reported. Generic databases on health loss could be developed alongside such efforts.

http://ift.tt/2tczqYn

Prevalence, incidence and aetiologies of pulmonary hypertension in Africa: a systematic review and meta-analysis protocol

Introduction

There are no data summarising the epidemiology of pulmonary hypertension (PH) among adults residing in Africa. Establishment of accurate epidemiological data on PH in this region may guide decision-making toward interventions to curb the burden of PH in Africa. The aim of this systematic review is to determine the prevalence, incidence and aetiologies of PH among people residing in Africa.

Methods and analysis

This systematic review and meta-analysis will follow the MOOSE guidelines for reporting. Relevant abstracts published until 30 September 2016 will be searched in PubMed/Medline, EMBASE (Excerpta Medica Database), African Journals Online and Africa Index Medicus. Full texts of eligible studies will then be accessed through PubMed, Google Scholar, HINARI and the respective journals' websites. Relevant unpublished papers and conference proceedings will also be checked. Data will be analysed using STATA version 13 software. The study-specific estimates will be pooled through a random-effects meta-analysis model to obtain an overall summary estimate of the prevalence/incidence and aetiologies of PH across studies. Heterogeneity of studies will be evaluated by the ² test on Cochrane's Q statistic. Funnel plot analysis and Egger's test will be done to detect publication bias. Results will be presented by geographical region (central, eastern, northern, southern and western Africa).

Ethics and dissemination

The current study is based on published data; ethical approval is, therefore, not required. This review will guide policy, practice and research by providing information on the magnitude of PH among people residing in Africa. Findings will be presented in evidence tables of individual studies as well as in summary tables. The final report of this systematic review, in the form of a scientific paper, will be published in a peer-reviewed journal. Furthermore, findings will be presented at conferences and submitted to relevant health authorities.

Review registration number

PROSPERO CRD42016049351.

http://ift.tt/2szDDHE

The emerging role of anamorelin hydrochloride in the management of patients with cancer anorexia-cachexia

Future Oncology Ahead of Print.


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Inhibition of the AKT/mTOR Pathway Augments the Anticancer Effects of Sorafenib in Thyroid Cancer

Cancer Biotherapy & Radiopharmaceuticals Jun 2017, Vol. 32, No. 5: 176-183.


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Molecular Targeted Drugs and Treatment of Colorectal Cancer: Recent Progress and Future Perspectives

Cancer Biotherapy & Radiopharmaceuticals Jun 2017, Vol. 32, No. 5: 149-160.


http://ift.tt/2txzz8c

Who can be a legitimate author on an article?

Publication date: Available online 16 June 2017
Source:Women and Birth
Author(s): Linda Sweet




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Treating ER+ Breast Cancer with CDK4/6 Inhibitors [News in Brief]

Targeted treatment improves progression-free survival, may reverse acquired resistance to endocrine therapy.

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A Subset of Gene Promoters Exhibit Both Promoter and Enhancer Activity [Research Watch]

Approximately 2%–3% of gene promoters also display distal enhancer activity (termed Epromoters).

http://ift.tt/2szL3La

Drug-Induced Epigenetic Reprogramming Promotes Drug Resistance [Research Watch]

Drug treatment causes resistance in cells with transiently high expression of drug resistance markers.

http://ift.tt/2txvGQE

Cyclin D3-CDK6 Has a Metabolic Prosurvival Role in T-ALL [Research Watch]

Cyclin D3–CDK6 inhibits the glycolytic enzymes PFK1 and PKM2 to prevent T-ALL cell apoptosis.

http://ift.tt/2szGAIq

Mismatch-Repair Deficiency Confers Sensitivity to Checkpoint Blockade [Research Watch]

PD-1 blockade with pembrolizumab achieves responses in 53% of patients with MMR-deficient tumors.

http://ift.tt/2txCoG6

Dabrafenib plus Trametinib Achieves Overall and Intracranial Responses [Research Watch]

Dabrafenib plus trametinib achieves intracranial responses in BRAF-mutant melanoma brain metastases.

http://ift.tt/2szDior

Clinical and molecular genetic features of cerebrotendinous xanthomatosis patients in Chinese families

Abstract

Cerebrotendinous xanthomatosis (CTX) is a lipid-storage disease caused by mutations in CYP27A1. Current publications of Chinese CTX were mainly based on case reports. Here we investigated the clinical manifestations, genetic features in Chinese CTX patients. The clinical materials of 4 Chinese CTX pedigrees were collected. The genetic testing was done by polymerase chain reaction plus Sanger sequencing. The features of Chinese CTX patients reported previously were also reviewed. Three novel mutations of p.Arg513Cys, c.1477-2A > C in family 1 and p.Arg188Stop in family 4 (NM 000784.3) in CYP27A1 were found. The probands in our study manifested cerebellar ataxia, tendon xanthoma and spastic paresis in family 1 and 4, tendon xanthoma plus spastic paraparesis in family 2, asymptomatic tendon xanthoma in family 3. Three known mutations of p.Arg137Gln, p.Arg127Trp and p.Arg405Gln were found respectively in Family 2, 3 and 4. For the Chinese patients reviewed, the most common findings were xanthomatosis (100%), pyramidal signs (100%), cerebellar ataxia (66.7%), cognitive impairment (66.7%), cataracts (50.0%), and peripheral neuropathy (33.3%). Chronic diarrhea was infrequently seen (5.6%). No mutation was found associated with any given clinical features. We identified 3 novel mutations in CYP27A1. In Chinese CTX patients, xanthomatosis was the most common symptom while cataracts and chronic diarrhea were less frequent. The special features in Chinese CTX patients might caused by the lack of serum cholestanol test and should be confirmed in larger number of patients in the future.

http://ift.tt/2txARQy

United States Medical Licensing Examination and American Board of Pediatrics Certification Examination Results: Does the Residency Program Contribute to Trainee Achievement

To determine whether training site or prior examinee performance on the US Medical Licensing Examination (USMLE) step 1 and step 2 might predict pass rates on the American Board of Pediatrics (ABP) certifying examination.

http://ift.tt/2sCBcVM

The Relationship between Dietary Intake, Growth, and Body Composition in Inborn Errors of Intermediary Protein Metabolism

To examine relationships between dietary intake, growth and body composition patterns in patients with inborn errors of intermediary protein metabolism and to determine a safe protein:energy ratio (P:E ratio) associated with optimal growth outcomes.

http://ift.tt/2sCLKUP

Generalized Pustular Psoriasis

A 6-year-old boy presented to our department with a 1-week history of generalized pustules with a high fever. It was suspected that he had pustular psoriasis when he was 8 months old. He had been treated with a topical dry distillation tar of delipidated soybean. The lesions were recurrent but had been under recent control. He had no recent history of infection or any new medication. Physical examination revealed multiple coalescing creamy-white pustules on a background of erythema over the whole body (Figure 1).

http://ift.tt/2tcJiBw

Sensitivity and Specificity of Empiric Treatment for Sexually Transmitted Infections in a Pediatric Emergency Department

To determine test characteristics of provider judgment for empiric antibiotic provision to patients undergoing testing for a sexually transmitted infection.

http://ift.tt/2tcirW5

Sudden Death in Epilepsy: Knowledge among Pediatric Providers

A survey of 146 pediatric care providers (PCPs) revealed that 75.3% were unaware that children with epilepsy were at risk of death, specifically from sudden unexpected (or unexplained) death in epilepsy (SUDEP). PCPs assume that the treating neurologist discusses these risks. Increasing PCPs' knowledge of SUDEP will help address the care gap related to informing families about SUDEP.

http://ift.tt/2tceTmR

Is childhood cardiometabolic status a risk factor from early infancy or toddler age?

In an analysis of cohorts of young children, Smego et al found that a body mass index (BMI) exceeding the 85th percentile in the first 4-6 months of life increases the risk of severe obesity by age 6 years by 2.5-fold.1 This finding is important because early identification and intervention in infants at risk for severe preschool-age obesity is critical, given that severe obesity associated with visceral fat deposition leads to comorbidities and is difficult to treat.2,3

http://ift.tt/2sCGAI9

Intestine-specific homeobox gene ISX integrates interleukin-6 signaling, tryptophan catabolism and immune suppression

The intestine-specific homeobox transcription factor ISX is an IL-6-inducible proto-oncogene implicated in the development of hepatocellular carcinoma (HCC), but its mechanistic contributions to this process are undefined. In this study, we provide evidence that ISX mediates a positive feedback loop integrating inflammation, tryptophan cataboism and immune suppression. We found that ISX mediated IL-6-induced expression of the tryptophan catabolic enzymes IDO1 and TDO2 in HCC cells, resulting in an ISX-dependent increase in the tryptophan catabolite kynurenine and its receptor aryl hydrocarbon receptor (AHR). Activation of this kynurenine/AHR signaling axis acted through a positive feedback mechanism to increase ISX expression and enhance cellular proliferation and tumorigenic potential. RNAi-mediated attenuation of ISX or AHR reversed these effects. In an IDO1-dependent manner, ectopic expression of ISX induced expression of genes encoding the critical immune modulators CD86 (B7-2) and PD-L1, through which ISX conferred a significant suppressive effect on the CD8+ T cell response. In HCC specimens, expression of IDO1, kynurenine, AHR and PD-L1 correlated negatively with survival. Overall, our results identified a feed-forward mechanism of immune suppression in HCC organized by ISX which involves kynurenine-AHR signaling and PD-L1, offering insights into immune escape by HCC which may improve its therapeutic management.

http://ift.tt/2tcgitm

The alkylating chemotherapeutic temozolomide induces metabolic stress in IDH1-mutant cancers and potentiates NAD+ depletion-mediated cytotoxicity

IDH1-mutant gliomas are dependent upon the canonical coenzyme nicotinamide adenine dinucleotide (NAD+) for survival. It is known that Poly(ADP-ribose) polymerase (PARP) activation consumes NAD+ during base excision repair (BER) of chemotherapy-induced DNA damage. We therefore hypothesized that a strategy combining NAD+ biosynthesis inhibitors with the alkylating chemotherapeutic agent temozolomide (TMZ) could potentiate NAD+ depletion-mediated cytotoxicity in mutant IDH1 cancer cells. To investigate the impact of TMZ on NAD+ metabolism, patient-derived xenografts and engineered mutant IDH1-expressing cell lines were exposed to TMZ, in vitro and in vivo, both alone and in combination with nicotinamide phosphoribosyltransferase (NAMPT) inhibitors, which block NAD+ biosynthesis. The acute time-period (<3 hrs) after TMZ treatment displayed a burst of NAD+ consumption driven by PARP activation. In IDH1 mutant-expressing cells, this consumption reduced further the abnormally-lowered basal steady-state levels of NAD+, introducing a window of hyper-vulnerability to NAD+ biosynthesis inhibitors. This effect was selective for IDH1-mutant cells and independent of methylguanine methyltransferase (MGMT) or mismatch repair (MMR) status, which are known rate-limiting mediators of adjuvant TMZ genotoxic sensitivity. Combined TMZ and NAMPT inhibition in an in vivo IDH1-mutant cancer model exhibited enhanced efficacy compared to each agent alone. Thus, we find IDH1-mutant cancers have distinct metabolic stress responses to chemotherapy-induced DNA damage and that combination regimens targeting non-redundant NAD+ pathways yield potent anti-cancer efficacy in vivo. Such targeting of convergent metabolic pathways in genetically-selected cancers could minimize treatment toxicity and improve durability of response to therapy.

http://ift.tt/2sCrHWk

p300-mediated acetylation of the Notch effector transcription factor Maml-1 recruits NACK to initiate Notch-dependent transcription

Although it has long been appreciated that p300 acts as a critical Notch coactivator, the mechanistic details of p300 in Notch-mediated transcription remain unclear. We previously demonstrated that PEAK1-related kinase activating pseudokinase 1 (NACK) is a critical co-activator of Notch signaling and binds to the Notch1 ternary complex. Herein we report that p300 and CBP acetylate mastermind-like transcriptional coactivator 1 (Maml1) on amino acid residues K188 and K189 to recruit NACK to the Notch1 ternary complex, which results in the recruitment of RNA polymerase II to initiate transcription. NACK was recruited to the ternary complexes containing Maml1 and Maml3, but not Maml2. Simultaneous inhibition of p300/CBP and Notch had a synergistic effect in esophageal adenocarcinoma. These results support the hypothesis that Notch transcriptional co-factors have selectivity for a specific Notch ternary complex, and they provide rationale and proof of concept for a combinatorial therapeutic attack on Notch-dependent cancers.

http://ift.tt/2tbTKJt

A genome-wide CRISPR screen identifies genes critical for resistance to FLT3 inhibitor AC220

Acute myeloid leukemia (AML) is a malignant hematopoietic disease and the most common type of acute leukemia in adults. The mechanisms underlying drug resistance in AML are poorly understood. Activating mutations in FMS-like tyrosine kinase 3 (FLT3) are the most common molecular abnormality in AML. Quizartinib (AC220) is a potent and selective second-generation inhibitor of FLT3. It is in clinical trials for the treatment of relapsed or refractory FLT3-ITD-positive and -negative AML patients and as maintenance therapy. To understand the mechanisms of drug resistance to AC220, we undertook an unbiased approach with a novel CRISPR pooled library to screen new genes whose loss of function confers resistance to AC220. We identified SPRY3, an intracellular inhibitor of FGF signaling, and GSK3, a canonical Wnt signaling antagonist, and demonstrated that re-activation of downstream FGF/Ras/ERK and Wnt signaling as major mechanisms of resistance to AC220. We confirmed these findings in primary AML patient samples. Expression of SPRY3 and GSK3A was dramatically reduced in AC220-resistant AML samples, and SPRY3-deleted primary AML cells were resistant to AC220. Intriguingly, expression of SPRY3 was greatly reduced in GSK3 knockout AML cells, which positioned SPRY3 downstream of GSK3 in the resistance pathway. Taken together, our study identified novel genes whose loss of function conferred resistance to a selective FLT3 inhibitor, providing new insight into signaling pathways that contribute to acquired resistance in AML.

http://ift.tt/2sCFQD9

A Naturally Generated Decoy of the Prostate Apoptosis Response-4 Protein Overcomes Therapy Resistance in Tumors

Primary tumors are often heterogeneous, composed of therapy-sensitive and emerging therapy-resistant cancer cells. Interestingly, treatment of therapy-sensitive tumors in heterogeneous tumor microenvironments results in apoptosis of therapy-resistant tumors. In this study, we identify a Par-4 amino-terminal fragment (PAF) that is released by diverse therapy-sensitive cancer cells following therapy-induced caspase cleavage of the tumor suppressor Par-4 protein. PAF caused apoptosis in cancer cells resistant to therapy and inhibited tumor growth. A VASA segment of Par-4 mediated its binding and degradation by the ubiquitin ligase Fbxo45, resulting in loss of Par-4 pro-apoptotic function. Conversely, PAF, which contains this VASA segment, competitively bound to Fbxo45 and rescued Par-4-mediated induction of cancer cell-specific apoptosis. Collectively, our findings identify a molecular decoy naturally generated during apoptosis that inhibits a ubiquitin ligase to overcome therapy resistance in tumors.

http://ift.tt/2tcgr02

Comparing the Intracarotid Amobarbital Test and Functional MRI for the Presurgical Evaluation of Language in Epilepsy

Abstract

Surgery is the treatment of choice for drug-resistant temporal lobe epilepsy (TLE). However, such surgery frequently causes deficits in language function, especially if performed on the dominant hemisphere. In recent years, the intracarotid amobarbital test (IAT) has been gradually replaced by functional magnetic resonance imaging (fMRI) in the preoperative identification of language areas to estimate the risk of postoperative language decline. In this paper, we review the neural substrates for language processing, how language impairment can result both from TLE itself and from surgical attempts to treat it. Subsequently, we discuss the strengths and limitations of, and current indications for fMRI and IAT during the preoperative workup, both by discussion of the studies that have evaluated them individually and through meta-analysis of data from 31 studies deemed eligible for analysis. Electrocortical stimulation mapping (ESM) is also discussed, as is the usefulness of the novel technique of resting-state fMRI. Finally, surgical techniques designed to avoid or reduce language decline in patients at risk are explored.

http://ift.tt/2rAV2jZ

Transcriptional Complexity and Distinct Expression Patterns of auts2 Paralogs in Danio rerio

Several genes that have been implicated in autism spectrum disorders are large and have multiple transcripts. Neurons are especially enriched with longer transcripts compared to non-neural cell types. The human autism susceptibility candidate 2 (AUTS2) gene is ~1.2 Mb long and is implicated in a number of neurological disorders including autism, intellectual disability, addiction and developmental delay. Recent studies show AUTS2 to be important for activation of transcription of neural specific genes, neuronal migration and neurite outgrowth. However, much remains to be understood regarding the transcriptional complexity and the functional roles of AUTS2 in neurodevelopment. Zebrafish provide an excellent model system for studying both these questions. We undertook genomic identification and characterization of auts2 and its paralogous genes in zebrafish. There are four auts2 family genes in zebrafish: auts2a, auts2b, fbrsl1 and fbrs. The absence of complete annotation of their structures hampers functional studies. We present evidence for transcriptional complexity of these four genes mediated by alternative splicing and alternative promoter usage. Furthermore, the expression of the various paralogs is tightly regulated both spatially and developmentally. Our findings suggest that auts2 paralogs serve distinct functions in the development and functioning of target tissues.

http://ift.tt/2rFHjn5

Sex Chromosome Evolution, Heterochiasmy and Physiological QTL in the Salmonid Brook Charr Salvelinus fontinalis

Whole genome duplication can have large impacts on genome evolution, and much remains unknown about these impacts. This includes the mechanisms of coping with a duplicated sex determination system and whether this has an impact on increasing the diversity of sex determination mechanisms. Other impacts include sexual conflict, where alleles having different optimums in each sex can result in sequestration of genes into non-recombining sex chromosomes. Sex chromosome development itself may involve sex-specific recombination rate (i.e. heterochiasmy), which is also poorly understood. Family Salmonidae is a model system for these phenomena, having undergone autotetraploidization and subsequent rediploidization in most of the genome at the base of the lineage. The salmonid master sex determining gene is known, and many species have non-homologous sex chromosomes, putatively due to transposition of this gene. In this study, we identify the sex chromosome of Brook Charr Salvelinus fontinalis and compare sex chromosome identities across the lineage (eight species, four genera). Although non-homology is frequent, homologous sex chromosomes and other consistencies are present in distantly related species, indicating probable convergence on specific sex and neo-sex chromosomes. We also characterize strong heterochiasmy with 2.7-fold more crossovers in maternal than paternal haplotypes with paternal crossovers biased to chromosome ends. When considering only rediploidized chromosomes, the overall heterochiasmy trend remains, although with only 1.9-fold more recombination in the female than the male. Y chromosome crossovers are restricted to a single end of the chromosome, and this chromosome contains a large interspecific inversion, although its status between males and females remains unknown. Finally, we identify QTL for 21 unique growth, reproductive and stress-related phenotypes to improve knowledge of the genetic architecture of these traits important to aquaculture and evolution.

http://ift.tt/2sb0rwY

Galanin suppresses proliferation of human U251 and T98G glioma cells via its subtype 1 receptor

Journal Name: Biological Chemistry
Issue: Ahead of print


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CXCL10 suppression of hem- and lymph-angiogenesis in inflamed corneas through MMP13

Abstract

Though not present in the normal adult cornea, both hem- and lymph-angiogenesis can be induced in this tissue after an inflammatory, infectious, or traumatic insult. We previously showed that the chemokine CXCL10 plays a key role in eradicating invading Candida (C.) albicans in C57BL6 mouse corneas. However, even after the clearance of pathogens, infection-induced inflammation and angiogenesis continue to progress in the cornea. The aim of this study is define the role of CXCL10 as a major angiostatic factor in modulating cornea angiogenesis in B6 mouse corneas under pathogenic conditions. We showed that epithelial expression of CXCL10, driven by AAV9 vector, suppressed both infection- and inflammation-induced hem and lymph angiogenesis, whereas the neutralization of CXCL10 as well as its receptor CXCR3 greatly promoted these processes. The inhibitory effect of CXCL10 was unrelated to its antimicrobial activity, but through the suppression of the expression of many angiogenic factors, including VEGFa and c, and MMP-13 in vivo. Inhibition of MMP13 but not TIMPs, attenuated suture-induced neovascularization but had no effects on CXCL10 expression. Strikingly, topical application of CXCL10 post-C. albicans infection effectively blocked both hem- and lymph-angiogenesis and preserved the integrity of sensory nerves in the cornea. Taken together, CXCL10 has strong inhibitory effects on neovascularization, whereas MMP13 is required for neovascularization in C. albicans-infected corneas and the local application of CXCL10 or MMP13 inhibitors, alone or as adjuvant therapy, may target hem- and lymph-angiogenesis in the inflamed corneas.

http://ift.tt/2sz4fIM

Conditioning and Robustness of RNA Boltzmann Sampling under Thermodynamic Parameter Perturbations

Understanding how RNA secondary structure prediction methods depend on the underlying nearest-neighbor thermodynamic model remains a fundamental challenge in the field. Minimum free energy (MFE) predictions are known to be "ill conditioned" in that small changes to the thermodynamic model can result in significantly different optimal structures. Hence, the best practice is now to sample from the Boltzmann distribution, which generates a set of suboptimal structures. Although the structural signal of this Boltzmann sample is known to be robust to stochastic noise, the conditioning and robustness under thermodynamic perturbations have yet to be addressed.

http://ift.tt/2rAg02k

Conditioning and Robustness of RNA Boltzmann Sampling under Thermodynamic Parameter Perturbations

Understanding how RNA secondary structure prediction methods depend on the underlying nearest-neighbor thermodynamic model remains a fundamental challenge in the field. Minimum free energy (MFE) predictions are known to be "ill conditioned" in that small changes to the thermodynamic model can result in significantly different optimal structures. Hence, the best practice is now to sample from the Boltzmann distribution, which generates a set of suboptimal structures. Although the structural signal of this Boltzmann sample is known to be robust to stochastic noise, the conditioning and robustness under thermodynamic perturbations have yet to be addressed.

http://ift.tt/2rAg02k

Tumour heterogeneity poses a significant challenge to cancer biomarker research

Tumour heterogeneity poses a significant challenge to cancer biomarker research

British Journal of Cancer advance online publication, June 15 2017. doi:10.1038/bjc.2017.171

Authors: Karolina Cyll, Elin Ersvær, Ljiljana Vlatkovic, Manohar Pradhan, Wanja Kildal, Marte Avranden Kjær, Andreas Kleppe, Tarjei S Hveem, Birgitte Carlsen, Silje Gill, Sven Löffeler, Erik Skaaheim Haug, Håkon Wæhre, Prasanna Sooriakumaran & Håvard E Danielsen

http://ift.tt/2tsJhsk

Extreme assay sensitivity in molecular diagnostics further unveils intratumour heterogeneity in metastatic colorectal cancer as well as artifactual low-frequency mutations in the KRAS gene

Extreme assay sensitivity in molecular diagnostics further unveils intratumour heterogeneity in metastatic colorectal cancer as well as artifactual low-frequency mutations in the KRAS gene

British Journal of Cancer advance online publication, June 15 2017. doi:10.1038/bjc.2017.170

Authors: Sara Mariani, Luca Bertero, Simona Osella-Abate, Cristiana Di Bello, Paola Francia di Celle, Vittoria Coppola, Anna Sapino, Paola Cassoni & Caterina Marchiò

http://ift.tt/2suDp4w

Selection-dependent and Independent Generation of CRISPR/Cas9-mediated Gene Knockouts in Mammalian Cells

Recent advances in the ability to genetically manipulate somatic cell lines hold great potential for basic and applied research. Here, we present two approaches for CRISPR/Cas9 generated knockout production and screening in mammalian cell lines, with and without the use of selectable markers.

http://ift.tt/2rzm0IV

Migration of the distal catheter of the ventriculoperitoneal shunt in hydrocephalus

There have been many reports on migration of the distal catheter of the ventriculoperitoneal shunt (VPS) since this phenomenon was recognized 50 years ago. However, there have been no attempts to analyze its different patterns or to assess these patterns in terms of potential risk to patients. We comprehensively reviewed all reports of distal VPS catheter migration indexed in PubMed and identified three different anatomical patterns of migration based on catheter extension and organs involved: (1) internal, when the catheter invades any viscus inside the thoracic, abdominal, or pelvic cavity; (2) external, when the catheter penetrates through the body wall either incompletely (subcutaneously) or completely (outside the body); and (3) compound, when the catheter penetrates a hollow viscus and protrudes through a pre-existing anatomical orifice. We also analyzed the association between each migration type and several key factors. External migration occurred mostly in infants. In contrast, internal migration occurred mostly in adults. A body wall weakness was not a risk factor for catheter protrusion. Shunt duration was a critical factor in the migration pattern, as most newly-replaced shunts tended to migrate externally. Clinicians must pay close attention to cases of large bowel perforation, since they were most often associated with intracranial infections. The organ involved in compound migration could determine the route of extrusion, as the bowel was involved in all trans-anal migrations and the stomach in most trans-oral cases. Clin. Anat., 2017. © 2017 Wiley Periodicals, Inc.

http://ift.tt/2ross0T

Visualization of the Axonal Projection Pattern of Embryonic Motor Neurons in Drosophila

This work details a standard immunohistochemistry method to visualize motor neuron projections of late stage-16 Drosophila melanogaster embryos. The filleted preparation of fixed embryos stained with FasII antibody provides a powerful tool to characterize the genes required for motor axon pathfinding and target recognition during neural development.

http://ift.tt/2taZDqb

Parents who lost child to heart disease placing AEDs around Ill. town

The Greg Holthaus Memorial Fund partnered with St. Joseph's Hospital to place AEDs near high schools

http://ift.tt/2twe7jU

Experimental study on the friction effect of plastic stent for biliary stone fragmentation (with video)

Abstract

Objectives

In patients with irretrievable or intractable bile duct stone, temporary insertion of plastic stent (PS) followed by further ERCP or surgery has been recommended as a "bridge" therapy. However, the exact mechanism of stone fragmentation has not been discovered. The aim of this study was to evaluate whether PS shape can facilitate stone fragmentation.

Methods

Using a new in vitro bile flow phantom model, we compared the friction effect among the three different PS groups (straight PS group; double pigtail-shaped PS group, and screw-shaped PS group) and the control group. Each group had 10 silicon tube rooms that separately contained one stone and two PS. The control group had 10 rooms each with only a stone and no PS. We performed an analysis of the friction effect by the stone weight and volume changes among the groups, excluding fragmented stones.

Results

After eight weeks, complete fragmentation was noted in one out of 34 cholesterol stones (2.9%), and four out of six pigmented stones (66.7%). They tended to be more prominent in the screw-shaped PS group than them they were in the straight PS group, double pigtail-shaped group, and control group (volume change: -11.33%, 7.94%, 4.43%, and 2.05%, respectively, p=0.1390; weight change: -9.30%, 0.71%, -0.10%, and -1.23%, respectively, p=0.3553).

Conclusion

Stone fragmentation may be induced by PS friction effect. Also, the screw-shaped plastic stents may improve friction effect. These results may help guide future PS development and clinical decisions.

This article is protected by copyright. All rights reserved.

http://ift.tt/2sy8Vi5

Feasibility study of personalized peptide vaccination for hepatocellular carcinoma patients refractory to loco-regional therapies

Summary

Overall survival (OS) of patients with hepatocellular carcinoma (HCC) refractory to loco-regional therapy is dismal even by treatment with sorafenib, a multi-kinase inhibitor. To develop a more efficacious treatment modality, we conducted a feasibility study of personalized peptide vaccination (PPV) for HCC, in which the peptides were selected from 31 peptide candidates based on the pre-existing immunity. Twenty-six HCC patients refractory to loco-regional therapies (Cohort 1) and 30 patients refractory to both loco-regional and systemic therapies (Cohort 2) were entered to the study. There were no severe adverse events related to PPV except for one injection site reaction. At the end of the 1^st cycle of 6 vaccinations, successful CTL or IgG boosting was observed in 57% or 46% in the Cohort 1 and in 54% or 52% in the Cohort 2, respectively. Successful IgG boosting at the end of 2^nd cycle was observed in the majority of patients tested. Median OS of the Cohort 1 or Cohort 2 was 18.7 months (M) (95%CI: 12.2-22.5 M) or 8.5 M (95% CI: 5.9-12.2 M), respectively. Based on the higher rates of immune boosting and safety profile of PPV, further clinical studies of PPV would be warranted for patients with HCC refractory to not only loco-regional therapy but also both loco-regional and systemic therapies.

This article is protected by copyright. All rights reserved.

http://ift.tt/2sy9dFN

How to record high-frequency oscillations in epilepsy: A practical guideline

Summary

Objective

Technology for localizing epileptogenic brain regions plays a central role in surgical planning. Recent improvements in acquisition and electrode technology have revealed that high-frequency oscillations (HFOs) within the 80–500 Hz frequency range provide the neurophysiologist with new information about the extent of the epileptogenic tissue in addition to ictal and interictal lower frequency events. Nevertheless, two decades after their discovery there remain questions about HFOs as biomarkers of epileptogenic brain and there use in clinical practice.

Methods

In this review, we provide practical, technical guidance for epileptologists and clinical researchers on recording, evaluation, and interpretation of ripples, fast ripples, and very high-frequency oscillations.

Results

We emphasize the importance of low noise recording to minimize artifacts. HFO analysis, either visual or with automatic detection methods, of high fidelity recordings can still be challenging because of various artifacts including muscle, movement, and filtering. Magnetoencephalography and intracranial electroencephalography (iEEG) recordings are subject to the same artifacts.

Significance

High-frequency oscillations are promising new biomarkers in epilepsy. This review provides interested researchers and clinicians with a review of current state of the art of recording and identification and potential challenges to clinical translation.

http://ift.tt/2sjpoVi

Comparison between chemoselection and definitive radiotherapy in patients with cervical esophageal squamous cell carcinoma

Abstract

Backgroud

Laryngeal preservation is an important consideration when treating cervical esophageal cancers (CECs) such as laryngeal cancer. The standard treatment for CEC allowing laryngeal preservation is chemoradiotherapy. However, in cases of laryngeal cancer, chemoselection has also been applied as a treatment strategy that promotes larynx preservation. This strategy involves assigning the appropriate radical treatment according to the primary tumor's response to induction chemotherapy. Since there have been no studies of the application of chemoselection in CEC cases, the present study compared the results, including laryngeal preservation rates, obtained upon applying chemoselection and chemoradiotherapy to CEC.

Study design

This was a retrospective cohort study of cervical esophageal squamous cell carcinoma patients treated using chemoselection or chemoradiotherapy at Aichi Cancer Center Hospital between January 2000 and March 2013. A total of 42 patients were enrolled.

Results

The 2-year overall survival and laryngeal preservation rates for the chemoselection group versus the primary radiotherapy group were 65.1 and 57.3 versus 40 and 83.3%, respectively (P = 0.017 and P = 0.122, respectively). The 2-year locoregional control rates for the chemoselection and primary radiotherapy groups were 68 and 25%, respectively (P = 0.045).

Conclusion

The chemoselection group achieved favorable results. Therefore, chemoselection can be applied as a treatment strategy for CEC.

http://ift.tt/2sB80ye

Investigating Emotional Spillover in the Brain

Life is full of emotional highs and lows, ranging from enjoying an activity with a loved one and savoring a delicious meal to feeling hurt by a negative interaction with a co-worker or that recent scuffle with a family member. But when we let emotions from one event carry on to the next, such spillover can color our impressions and behavior in those new situations – sometimes for the worse.

Researchers at the Center for Healthy Minds at the University of Wisconsin–Madison are discovering what happens in the brain when such emotional spillover occurs and, for the first time, are able to pinpoint areas directly responsible. Their findings are published in Psychological Science, a journal of the Association for Psychological Science.

Using Transcranial Magnetic Stimulation (TMS), a technique that produces a magnetic field that can temporarily "knock out" or inhibit activity in specific parts of the brain, the team discovered that when the lateral prefrontal area of the brain (a region known for executive function) was inhibited by the stimulation, participants showed more emotional spillover. In the experiment, they measured this by collecting people's ratings and first impressions of neutral faces they saw immediately after faces that were smiling (prompting positive emotions) or fearful (prompting negative emotions).

The findings, supported by a grant from the National Institute of Mental Health, are part of larger efforts to understand the complexity of the brain and what types of mental training or activities can best improve emotional reactions known to promote higher levels of well-being. TMS therapy is approved for depression by the FDA, and this work may shed light on why stimulating parts of the prefrontal cortex is successful in improving the ability to regulate negative emotions.

"It was interesting because participants saw the emotional faces very briefly," says Regina Lapate, Center for Healthy Minds collaborator and current postdoctoral researcher at the University of California, Berkeley, who led the work. "And when asked afterward, they didn't think that they had been influenced by it in their ratings. Having their prefrontal cortex disrupted generated spillover onto their unrelated events that followed. Emotional spillover can happen without us being aware of it."

The team discovered that when the lateral prefrontal cortex was intact (when the brain was not inhibited by TMS), the person did not show spillover when viewing subsequent neutral faces. And when the opposite occurred – when the lateral prefrontal cortex was inhibited by TMS, emotional spillover occurred more frequently and with greater intensity. Three days later outside of the laboratory, participants still showed that emotional bias when asked to rate the same neutral faces, suggesting that the negative emotional spillover they first showed in the laboratory produced long-lasting, biased first impressions.

"If your first impression of someone is formed when you're experiencing emotional spillover from a previous context, that negative impression may stick," Lapate adds.

In addition, research on mindfulness meditation has been suggested to improve emotion regulation and connectivity between the prefrontal cortex and more emotion-centered areas of the brain such as the amygdala. If scientists know that there's a causal relationship between these areas of the brain, they can more accurately tailor interventions to target these areas and improve well-being.

"We are excited about this experiment because it demonstrates the causal role of the prefrontal cortex in regulating emotional behavior," says Richard Davidson, William and James Vilas Professor of Psychology and Psychiatry who worked on the study and directs the Center for Healthy Minds. "It invites the possibility that strategies that promote prefrontal engagement may have beneficial consequences for emotion regulation."

Next on Lapate's agenda is to test whether the reverse works – can TMS stimulation that increases neural firing in the prefrontal cortex lead to a decrease in negative emotional spillover? At the University of California, Berkeley, she'll continue exploring that question as well as how the lateral prefrontal cortex as a whole changes the neural coding for positive and negative information.

Meanwhile, the team at UW–Madison will further examine how contemplative practices may change emotional spillover and target these areas as measured by neural activity recorded in a brain scanner.

In addition to Lapate and Davidson, co-authors on the study include Jason Samaha, Bas Rokers, Hamdi Hamzah, and Bradley R. Postle of the University of Wisconsin-Madison.

This study was supported by National Institute of Mental Health Grants R01-MH43454 (to R. J. Davidson), P50-MH069315 (to R. J. Davidson), F32-MH113347 (to R. C. Lapate), and MH095984 (to B. R. Postle).

All materials have been made publicly available via Open Science Framework. The complete Open Practices Disclosure for this article is available online. This article has received the badge for Open Materials.

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Table of Contents

Publication date: July 2017
Source:The Spine Journal, Volume 17, Issue 7





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Table of Contents

Publication date: July 2017
Source:The Spine Journal, Volume 17, Issue 7





http://ift.tt/2sjxcWW

Table of Contents

Publication date: July 2017
Source:The Spine Journal, Volume 17, Issue 7





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Is the clinical cervical extensor endurance test capable of differentiating the local and global muscles?

Publication date: July 2017
Source:The Spine Journal, Volume 17, Issue 7
Author(s): Amir H. Kahlaee, Asghar Rezasoltani, Leila Ghamkhar
Background ContextDifferential alterations have been reported in the local and global cervical muscles in the presence of chronic neck pain (CNP), including the endurance alterations of these muscles. Identifying the involved muscles is crucial to the assessment and rehabilitation of patients with CNP.PurposeTo assess the relationship between clinical endurance test results, pain and disability indices, and ultrasonographic (US) measurements of the neck extensor muscles; to compare the deep and superficial cervical extensor muscle endurance and size of CNP patients with those of asymptomatic subjects and to compare the relationship between local and global extensor endurance with US measures, pain intensity, and disability.Study Design/SettingCross-sectional correlational analysis with a case-control design.Patient SampleThirty patients with CNP and 30 asymptomatic subjects participated in this study.Outcome MeasuresEndurance, thickness, cross-sectional area, and shape ratio of the cervical extensor muscles (splenius capitis [SpCap], semispinalis capitis [SSCap], semispinalis cervicis [SSCer], and multifidus [MF]); pain intensity measured by the visual analog scale (VAS); neck disability index (NDI); correlation between US measures, pain intensity and NDI and extensor endurance; and correlation of US measures with pain intensity and NDI.MethodsThe deep and superficial cervical extensor muscle endurance and dimensions were measured via a clinical test and by US, respectively. Participants were asked to hold the neutral chin-tuck position while lying prone. The test would be terminated if the head moved into either flexion or extension, which would yield "global" or "local" extensor muscle endurance, respectively.ResultsThe CNP patients showed lower global extensor endurance levels than the control participants (p<.05). The US measures of the deep extensor muscles were also smaller in the CNP group (p<.05). There were no significant correlations between extensor endurance test results and US measures in either group except for the SSCap muscle size with local and total endurance (p=.04 for both) of CNP and control participants, respectively. NDI was correlated with SpCap and SSCer muscle thicknesses in a positive and negative manner, respectively (p=.03 for both). There was also a significant correlation between MF size and VAS (p<.05).ConclusionsThe findings showed higher levels of global muscle fatigability and smaller size of deep neck extensor muscles in CNP patients. Disability and extensor endurance were found to be associated with extensor muscle size. The results challenge the validity of the clinical extensor muscle endurance test in the differentiation of the deep and superficial extensor muscle endurance and the use of US in the assessment of cervical muscle endurance. Further investigations are needed to judge the superficial and deep muscle endurance in CNP patients.



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Editorial Board

Publication date: July 2017
Source:The Spine Journal, Volume 17, Issue 7





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Is the use of minimally invasive fusion technologies associated with improved outcomes after elective interbody lumbar fusion? Analysis of a nationwide prospective patient-reported outcomes registry

Publication date: July 2017
Source:The Spine Journal, Volume 17, Issue 7
Author(s): Matthew J. McGirt, Scott L. Parker, Praveen Mummaneni, John Knightly, Deborah Pfortmiller, Kevin Foley, Anthony L. Asher
Background ContextOver the last decade, clinical investigators and biomedical industry groups have used significant resources to develop advanced technologies that enable less invasive spine fusions. These minimally invasive surgery (MIS) technologies often require increased expenditures by hospitals and payers. Although several small single center studies have suggested MIS technologies decrease surgical morbidity and reduce hospital stay, evidence documenting benefit from a patient perspective remains limited. Furthermore, MIS outcomes have yet to be evaluated from the perspective of multiple practice types representing the broad spectrum of US spine surgery.PurposeThis study aimed to examine a population of patients who underwent one- or two-level interbody lumbar fusion diagnosed with lumbar stenosis or Grade 1 spondylolisthesis in an observational, prospective national registry for the purposes of determining how MIS and traditional open technologies affect postsurgical and patient-reported outcomes (PROs).Study Design/SettingThis study used observational analysis of prospectively collected data.Patient SampleThe sample consisted of cases from the National Neurosurgery Quality and Outcomes Database (N²QOD).Outcome MeasuresNumeric rating scale for back and leg pain, Oswestry Disability Index, EuroQol-5D, return to work, and perioperative morbidity were the outcome measures.MethodsThe N²QOD is a prospective PROs registry enrolling patients undergoing elective spine surgery from 60 hospitals in 27 US states via representative sampling. We analyzed the N²QOD aggregate dataset (2010–2014) to identify one- and two-level lumbar interbody fusion procedures performed for lumbar stenosis or Grade 1 spondylolisthesis with 12 months' follow-up where surgical instrumentation and implant types were clearly identified. Perioperative and 1-year outcomes were compared between cases performed with MIS enabling technologies versus traditional open technologies before and after propensity matching.ResultsThere were 467 (24%) patients who underwent elective interbody lumbar fusion using MIS enabling technologies whereas 1,480 (76%) underwent the procedure using traditional open technologies. The MIS patients were slightly healthier (American Society of Anesthesiologists grade), had private insurance more frequently, and underwent two-level fusion less frequently. Unmatched, the MIS cohort was associated with reduced blood loss, a 0.7-day reduction in mean length of hospital stay, and 5% reduced need for post-discharge inpatient rehabilitation, but equivalent 90-day safety measures. After propensity matching, the MIS cohort remained associated with reduced blood loss and a shorter length of stay for one-level fusion (p<.05) but had equivalent length of stay for two-level fusion. Outcomes in all other 90-day safety measures were similar. In both unadjusted and propensity-matched comparison, MIS versus open technologies were associated with equivalent return to work, patient-reported pain, physical disability, and quality of life at 3 and 12 months' follow-up.ConclusionsIn a representative sampling registry of elective interbody lumbar spine fusion procedures spanning 27 US states, nearly a quarter of procedures performed from 2010 to 2014 used minimally invasive enabling technologies. Regardless of approach, interbody lumbar fusion was associated with significant and sustained improvements in all measured health domains. When used in everyday care by a wide spectrum of spine surgeons in non-research settings, the use of MIS technologies was associated with reduced intraoperative blood loss but only a half-day reduction in mean length of hospital stay for one-level fusions. Minimally invasive surgery was not associated with any improved perioperative safety measures or 12-month outcomes. Although MIS enabling technologies may increase some in-hospital care efficiencies, MIS clinical outcomes are similar to open surgery for patients undergoing one- and two-level interbody lumbar fusions.



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Does sedentary behavior increase the risk of low back pain? A population-based co-twin study of Spanish twins

Publication date: July 2017
Source:The Spine Journal, Volume 17, Issue 7
Author(s): Anita B. Amorim, Gavin M. Levy, Francisco Pérez-Riquelme, Milena Simic, Evangelos Pappas, Amabile B. Dario, Manuela L. Ferreira, Eduvigis Carrillo, Alejandro Luque-Suarez, Juan R. Ordoñana, Paulo H. Ferreira
BackgroundThe relationship between sedentary lifestyle and low back pain (LBP) remains unclear and previous research has not accounted for genetic and early environmental factors.PurposeOur aim was to investigate if sedentary behavior is associated with the lifetime prevalence of persistent LBP and the risk of developing persistent LBP, care-seeking due to LBP, and activity limiting LBP when genetics and early environmental factors are accounted for.Study DesignBoth cross-sectional and longitudinal designs with a within-pair twin case-control were implemented.Patient SampleThere were 2,148 twins included in the cross-sectional analysis whereas 1,098 twins free of persistent LBP at baseline were included in the longitudinal analysis.Outcome MeasuresSedentary behavior was the explanatory variable. Lifetime prevalence of LBP was the outcome variable in the cross-sectional analysis. The incidence of persistent LBP, care-seeking due to LBP, and activity limiting LBP were the outcome variables for the longitudinal analysis.MethodsThis observational study was supported by a grant in 2012. No competing interests were declared.ResultsIn the cross-sectional analysis, sedentary behavior was slightly associated with an increased prevalence of persistent LBP in females but not in males. This association was not apparent when genetics and early environmental factors were accounted for. We acknowledge that the small sample included in the co-twin analyses have yielded wide confidence intervals, and that caution should be exercised when interpreting and an association may not be ruled out. In the longitudinal analysis, sedentary behavior did not significantly increase the risk of persistent LBP, care-seeking due to LBP, or activity limiting LBP.ConclusionsSedentary behavior is associated with concurrent LBP. However, this association is weak; it only appears in females and decreases when accounting for genetics. Future studies using a twin design with larger samples should be conducted to further test these findings.



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Are patient-reported outcomes predictive of patient satisfaction 5 years after anterior cervical spine surgery?

Publication date: July 2017
Source:The Spine Journal, Volume 17, Issue 7
Author(s): Gregory D. Schroeder, Dom Coric, Han Jo Kim, Todd J. Albert, Kris E. Radcliff
Background ContextPatient satisfaction is becoming an increasing common proxy for surgical quality; however, the correlation between patient satisfaction and surgical outcomes 2 and 5 years after anterior cervical surgery has not been evaluated.PurposeThe study aimed to determine if patient satisfaction is predicted by improvement in patient-reported outcomes (PRO) 2 and 5 years after anterior cervical spine surgery.Study DesignThis is a retrospective analysis of prospectively collected data.Patient SampleThe sample included patients enrolled in the Food and Drug Administration investigational device exemption clinical trial comparing total disc replacement with Mobi-C cervical artificial disc and anterior cervical discectomy and fusion.Outcome MeasuresThe outcome measures were visual analog scale (VAS) neck pain score, Neck Disability Index (NDI), and Short-Form 12-Item scores, as well as patient satisfaction.MethodsReceiver operating characteristic curves were used to determine if improvement in different PRO metrics can accurately identify patient satisfaction. Additionally, a logistic regression analysis was performed on the results at 24 months and 60 months to identify independent predictors of patient satisfaction. This research was supported by LDR (Zimmer Biomet) 13785 Research Boulevard - Suite 200 Austin, TX 78750.ResultsData were available for 512 patients at 60 months. At 24 months postoperatively, NDI score improvement (area under the curve [AUC]=0.806), absolute NDI score (AUC=0.823), and absolute VAS neck pain score (AUC=0.808) were all excellent predictors of patient satisfaction. At 60 months postoperatively, NDI score improvement (AUC=0.815), absolute NDI score (AUC=0.839), VAS neck pain score improvement (AUC=0.803), and absolute VAS neck pain score (AUC=0.861) were all excellent predictors of patient satisfaction.ConclusionsIn patients undergoing one- and two-level anterior cervical spine surgery, between 2 and 5 years postoperatively, patient satisfaction is significantly predicted by PROs, including the VAS neck score and the NDI.



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Most efficient questionnaires to measure quality of life, physical function, and pain in patients with metastatic spine disease: a cross-sectional prospective survey study

Publication date: July 2017
Source:The Spine Journal, Volume 17, Issue 7
Author(s): Nuno Rui Paulino Pereira, Stein J. Janssen, Kevin A. Raskin, Francis J. Hornicek, Marco L. Ferrone, John H. Shin, Jos A.M. Bramer, Cornelis Nicolaas van Dijk, Joseph H. Schwab
Background ContextAssessing quality of life, functional outcome, and pain has become important in assessing the effectiveness of treatment for metastatic spine disease. Many questionnaires are able to measure these outcomes; few are validated in patients with metastatic spine disease. As a result, there is no consensus on the ideal questionnaire to use in these patients.PurposeOur study aim was to assess whether certain questionnaires measuring quality of life, functional outcome, and pain (1) correlated with each other, (2) measured the construct they claim to measure, (3) had good coverage—floor and ceiling effects, (4) were reliable, and (5) whether there were differences in completion time between them.DesignThis is a prospective cross-sectional survey study from three outpatient clinics (two orthopedic oncology clinics and one neurosurgery clinic) from two affiliated tertiary hospital care centers.Patient SampleWe included 100 consecutive patients with metastatic spine disease between July 2014 and February 2016. We excluded non–English-speaking patients.Outcome MeasuresThe following questionnaires were given in random order: Oswestry Disability Index (ODI) or Neck Disability Index (NDI), Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function, PROMIS Pain Intensity, EuroQol-5 Dimensions (EQ-5D), and the Spine Oncology Study Group Outcome Questionnaire (SOSG-OQ).MethodsWe used exploratory factor analysis—correlating questionnaires with an underlying mathematically derived trait—to assess if questionnaires measured the same concept. Coverage was assessed by floor and ceiling effects, and reliability was assessed by standard error of measurement as a function of ability. Differences in completion times were tested using the Friedman test.ResultsQuestionnaires measured the construct they were developed for, as demonstrated with high correlations (>0.7) with the underlying trait. A floor effect was present in the PROMIS Pain Intensity (7.0%), ODI or NDI (4.0%), and the PROMIS Physical Function (1.0%) questionnaires. A ceiling effect was present in the EQ-5D questionnaire (6.0%). The SOSG-OQ had no floor or ceiling effect. The PROMIS Physical Function and PROMIS Pain Intensity proved to be the most reliable, whereas the EQ-5D was the least reliable. Completion time differed among questionnaires (p<.001) and was shortest for the PROMIS Pain Intensity (median 24 seconds) and PROMIS Physical Function (median 42 seconds).ConclusionsIn patients with metastatic spine disease, we recommend the SOSG-OQ for measuring quality of life, the PROMIS Physical Function for measuring physical function, and the PROMIS Pain Intensity for measuring pain.



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Rod stiffness as a risk factor of proximal junctional kyphosis after adult spinal deformity surgery: comparative study between cobalt chrome multiple-rod constructs and titanium alloy two-rod constructs

Publication date: July 2017
Source:The Spine Journal, Volume 17, Issue 7
Author(s): Sanghyun Han, Seung-Jae Hyun, Ki-Jeong Kim, Tae-Ahn Jahng, Subum Lee, Seung-Chul Rhim
Background ContextLittle is known about the effect of rod stiffness as a risk factor of proximal junctional kyphosis (PJK) after adult spinal deformity (ASD) surgery.PurposeThe aim of this study was to compare radiographic outcomes after the use of cobalt chrome multiple-rod constructs (CoCr MRCs) and titanium alloy two-rod constructs (Ti TRCs) for ASD surgery with a minimum 1-year follow-up.Study DesignRetrospective case-control study in two institutes.Patient SampleWe included 54 patients who underwent ASD surgery with fusion to the sacrum in two academic institutes between 2002 and 2015.Outcome MeasuresRadiographic outcomes were measured on the standing lateral radiographs before surgery, 1 month postoperatively, and at ultimate follow-up. The outcome measures were composed of pre- and postoperative sagittal vertical axis (SVA), pre- and postoperative lumbar lordosis (LL), pre- and postoperative thoracic kyphosis (TK)+LL+pelvic incidence (PI), pre- and postoperative PI minus LL, level of uppermost instrumented vertebra (UIV), evaluation of fusion after surgery, the presence of PJK, and the occurrence of rod fracture.Materials and MethodsWe reviewed the medical records of 54 patients who underwent ASD surgery. Of these, 20 patients had CoCr MRC and 34 patients had Ti TRC. Baseline data and radiographic measurements were compared between the two groups. The Mann-Whitney U test, the chi-square test, and the Fisher exact test were used to compare outcomes between the groups.ResultsThe patients of the groups were similar in terms of age, gender, diagnosis, number of three-column osteotomy, levels fused, bone mineral density, preoperative TK, pre- and postoperative TK+LL+PI, SVA difference, LL change, pre- and postoperative PI minus LL, and location of UIV (upper or lower thoracic level). However, there were significant differences in the occurrence of PJK and rod breakage (PJK: CoCr MRC: 12 [60%] vs. Ti TRC: 9 [26.5%], p=.015; occurrence of rod breakage: CoCr MRC: 0 [0%] vs. Ti TRC: 11 [32.4%], p=.004). The time of PJK was less than 12 months after surgery in the CoCr MRC group. However, 55.5% (5/9) of PJK developed over 12 months after surgery in the Ti TRC group.ConclusionsIncreasing the rod stiffness by the use of cobalt chrome rod and can prevent rod breakage but adversely affects the occurrence and the time of PJK.



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The change of adjacent segment after cervical disc arthroplasty compared with anterior cervical discectomy and fusion: a meta-analysis of randomized controlled trials

Publication date: Available online 15 June 2017
Source:The Spine Journal
Author(s): Liang Dong, Zhengwei Xu, Xiujin Chen, Dongqi Wang, Dichen Li, Tuanjing Liu, Dingjun Hao
Backgroud ContextMany meta-analyses have been performed to study the efficacy of cervical disc arthroplasty (CDA) compared with anterior cervical discectomy and fusion (ACDF); however, there are few data referring to adjacent segment within these meta-analyses, or investigators are unable to arrive at the same conclusion in the few meta-analyses about adjacent segment. With the increased concerns surrounding adjacent segment degeneration (ASDeg) and adjacent segment disease (ASDis) after anterior cervical surgery, it is necessary to perform a comprehensive meta-analysis to analyze adjacent segment parameters.PurposeTo perform a comprehensive meta-analysis to elaborate adjacent segment motion, degeneration, disease, and reoperation of CDAcompared with ACDF.Study DesignMeta-analysis of randomized controlled trials (RCTs).Materials and MethodsPubmed, EMbase, and Cochrane Library were searched for RCTs comparing CDA and ACDF before May 2016. The analysis parameters included: follow-up time, operative segments, adjacent segment motion, ASDeg, ASDis and adjacent segment reoperation. The risk of bias scale was used to assess the papers. Subgroup analysis and sensitivity analysis were used to analyze the reason for high heterogeneity.ResultsTwenty-nine RCTs fulfilled the inclusion criteria. Compared with ACDF, the rate of adjacent segment reoperation in the CDA group was significantly lower (P < 0.01), and the advantage of that group in reducing adjacent segment reoperation increase with increasing of follow-up time by subgroup analysis. There was no statistically significant difference in ASDeg between CDA and ACDF within the 24-month follow-up period; however, the rate of ASDeg in CDA was significantly lower than that of ACDF with the increase in follow-up time (P < 0.01). There was no statistically significant difference in ASDis between CDA and ACDF (P > 0.05). CDA provided a lower adjacent segment range of motion (ROM) than did ACDF, but the difference was not statistically significant.ConclusionsCompared with ACDF, the advantages of CDA were lower ASDeg and adjacent segment reoperation. However, there was no statistically significant difference in ASDis and adjacent segment ROM.



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A questionable conclusion by Ido Stahl et al.

Publication date: July 2017
Source:The Spine Journal, Volume 17, Issue 7
Author(s): Zehao Jing, Feng Nan, Jianli Dong, Fanqi Meng, Youzhi Song, Tonglin Xia




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Reply to letter to the editor titled “a questionable conclusion by Ido Stahl et al.”

Publication date: July 2017
Source:The Spine Journal, Volume 17, Issue 7
Author(s): Ido Stahl, Elias Haddad, Nir Hous, Daniel Dreyfuss




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Meetings Calendar

Publication date: July 2017
Source:The Spine Journal, Volume 17, Issue 7





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Slow Interconversion in a Heterogeneous Unfolded-State Ensemble of Outer-Membrane Phospholipase A

Structural and dynamic investigations of unfolded proteins are important for understanding protein-folding mechanisms as well as the interactions of unfolded polypeptide chains with other cell components. In the case of outer-membrane proteins (OMPs), unfolded-state properties are of particular physiological relevance, because these proteins remain unfolded for extended periods of time during their biogenesis and rely on interactions with binding partners to support proper folding. Using a combination of ensemble and single-molecule spectroscopy, we have scrutinized the unfolded state of outer-membrane phospholipase A (OmpLA) to provide a detailed view of its structural dynamics on timescales from nanoseconds to milliseconds.

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Effects of Inhibiting VPS4 Support a General Role for ESCRTs in Extracellular Vesicle Biogenesis

Extracellular vesicles (EVs) are proposed to play important roles in intercellular communication. Two classes of EVs can be distinguished based on their intracellular origin. Exosomes are generated within endosomes and released when these fuse with the plasma membrane, whereas ectosomes bud directly from the plasma membrane. Studies of EV function have been hindered by limited understanding of their biogenesis. Components of the endosomal sorting complex required for transport (ESCRT) machinery play essential roles in topologically equivalent processes at both the endosome and the plasma membrane and are consistently recovered in EVs, but whether they are generally required to produce EVs is still debated.

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Comprehensive DNA Methylation Analysis Using a Methyl-CpG-binding Domain Capture-based Method in Chronic Lymphocytic Leukemia Patients

This work describes an optimized methyl-CpG-binding domain (MBD) sequencing protocol and a computational pipeline to identify differentially methylated CpG-rich regions in chronic lymphocytic leukemia (CLL) patients.

http://ift.tt/2sBtkUv

DiI Perfusion as a Method for Vascular Visualization in Ambystoma mexicanum

Using a lipophilic 1,1'-Dioctadecy-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) staining technique, Ambystoma mexicanum can undergo vascular perfusion to allow for easy visualization of the vasculature.

http://ift.tt/2sBpgDB

The risk of hepatocellular carcinoma is decreasing after the first 5 years of entecavir or tenofovir in Caucasians with chronic hepatitis B

ABSTRACT

Whether there is a change of hepatocellular carcinoma (HCC) incidence in chronic hepatitis B (CHB) patients under long-term therapy with potent nucleos(t)ide analogues is currently unclear. We therefore assessed the HCC incidence beyond year 5 of entecavir/tenofovir therapy and tried to determine possible factors associated with late HCC occurrence. This European 10-center, cohort study included 1951 adult Caucasian CHB patients without HCC at baseline who received entecavir/tenofovir for ≥1 year. Of them, 1205 (62%) patients without HCC within the first 5 years of therapy have been followed for 5-10 (median: 6.8) years. HCCs have been diagnosed in 101/1951 (5.2%) patients within the first 5 years and 17/1205 (1.4%) patients within 5-10 years. The yearly HCC incidence rate was 1.22% within and 0.73% after the first 5 years (p=0.050). The yearly HCC incidence rate did not differ within and after the first 5 years in non-cirrhotics (0.49% vs 0.47%, P=0.931), but it significantly declined in cirrhotics (3.22% vs 1.57%, p=0.039). All HCCs beyond year 5 developed in patients older than 50 years at entecavir/tenofovir onset. Older age, lower platelets at baseline and year 5 and liver stiffness ≥12 kPa at year 5 were independently associated with more frequent HCC development beyond year 5 in multivariable analysis. No patient with low PAGE-B score at baseline or year 5 developed HCC. In conclusion, the HCC risk is decreasing beyond year 5 of entecavir/tenofovir therapy in Caucasian CHB patients, particularly in those with compensated cirrhosis. Older age, especially age ≥50 years, lower platelets and liver stiffness ≥12 kPa at year 5 represent the main risk factors for late HCC development. This article is protected by copyright. All rights reserved.

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Blockade of CD112R and TIGIT signaling sensitizes human natural killer cell functions

Abstract

Trastuzumab is the first-line drug to treat breast cancer with high Her2 expression. However, many cancers failed to respond, largely due to their resistance to NK cell-triggered antibody-dependent cellular cytotoxicity (ADCC). Poliovirus receptor (PVR)-like molecules are known to be important for lymphocyte functions. We found that all PVR-like receptors are expressed on human NK cells, and only TIGIT is preferentially expressed on the CD16+ NK cell subset. Disrupting the interactions of PVR-like receptors with their ligands on cancer cells regulates NK cell activity. More importantly, TIGIT is upregulated upon NK cell activation via ADCC. Blockade of TIGIT or CD112R, separately or together, enhances trastuzumab-triggered antitumor response by human NK cells. Thus, our findings suggest that PVR-like receptors regulate NK cell functions and can be targeted for improving trastuzumab therapy for breast cancer.

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A better angel of our nature: Hanna Michel “Jean” Khoury, MD (April 24, 1967–May 22, 2017)

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Discerning quality: an analysis of informed consent documents for common cardiovascular procedures

Introduction

Informed consent provides a powerful opportunity to build trust between the patient and clinician while supporting patient autonomy, transparency and shared decision-making.12 However, it is often relegated to a perfunctory task, performed as an ethical-legal formality minutes prior to a procedure.3–5 As such, basic elements necessary for achieving the espoused goals of informed consent may be missing or suboptimally implemented, undermining patient-centred, high-quality decision-making. The types and extent of gaps in quality have not been systematically studied, limiting efforts to improve implementation. Our aim was to assess variation in quality of informed consent documents associated with three commonly performed cardiovascular procedures: left heart catheterisation, transesophageal echocardiography and implantation of a cardioverter defibrillator. We focused on basic elements of consent documents with the goal of illuminating opportunities to establish minimum standards for informed consent.

Methods...

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When patient-centred care is worth doing well: informed consent or shared decision-making

High quality care is patient-centred.1 Efforts to promote patient-centred care in clinical practice should improve quality. Both shared decision-making (SDM) and the process of obtaining informed consent could be expressions of patient-centred care—to the extent that they respond to the advocates' call for 'nothing about me without me'. In this issue of BMJ Quality and Safety, Shahu et al2 discuss variations in the quality of informed consent procedures, which could, in their view, fail to support patient-centred care in general, and SDM specifically.

Readers interested in advancing this domain of quality may, therefore, be interested in improving the quality of informed consent procedures and promoting the implementation and routine use of SDM. But are these similar practices? Is informed consent a lesser version of SDM, with SDM the ideal expression of patient autonomy and involvement? Or are these different in purpose, process and outcomes?

Informed...

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What can a participatory approach to evaluation contribute to the field of integrated care?

Better integration of care within the health sector and between health and social care is seen in many countries as an essential way of addressing the enduring problems of dwindling resources, changing demographics and unacceptable variation in quality of care. Current research evidence about the effectiveness of integration efforts supports neither the enthusiasm of those promoting and designing integrated care programmes nor the growing efforts of practitioners attempting to integrate care on the ground. In this paper we present a methodological approach, based on the principles of participatory research, that attempts to address this challenge. Participatory approaches are characterised by a desire to use social science methods to solve practical problems and a commitment on the part of researchers to substantive and sustained collaboration with relevant stakeholders. We describe how we applied an emerging practical model of participatory research, the researcher-in-residence model, to evaluate a large-scale integrated care programme in the UK. We propose that the approach added value to the programme in a number of ways: by engaging stakeholders in using established evidence and with the benefits of rigorously evaluating their work, by providing insights for local stakeholders that they were either not familiar with or had not fully considered in relation to the development and implementation of the programme and by challenging established mindsets and norms. While there is still much to learn about the benefits and challenges of applying participatory approaches in the health sector, we demonstrate how using such approaches have the potential to help practitioners integrate care more effectively in their daily practice and help progress the academic study of integrated care.

http://ift.tt/2taPlGA

Nursing skill mix and patient outcomes

In hospitals, the nursing staff typically represent the largest single element of cost, and nursing is frequently treated as a cost centre rather than a core service line. Efforts to contain hospital costs often involve cutting nursing care, reducing the number of nurses or replacing some professional nursing staff with staff such as licensed practical nurses, nurses' aides and other assistive personnel.

Substantial evidence from studies in the USA, Europe and other countries relates lower nurse staffing and higher nurse workloads to adverse patient outcomes such as mortality, infections, falls and longer lengths of stay. Longer stays, which increase hospital costs, may result from increased adverse events lengthening admissions or delays in care due to nurses being unable to complete their work or prepare patients for discharge.1–13

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What we know about designing an effective improvement intervention (but too often fail to put into practice)

Intervening to change health system performance for the better

It is temptingly easy to treat improvement interventions as if they are drugs—technical, stable and uninfluenced by the environment in which they work. Doing so makes life so much easier for everyone. It allows improvement practitioners to plan their work with a high degree of certainty, funders to be confident that they know what they are buying and evaluators to focus on what really matters—whether or not 'it' works.

But of course most people know that life is not as simple as that. Experienced improvers have long recognised that interventions—the specific tools and activities introduced into a healthcare system with the aim of changing its performance for the better1—flex and morph. Clever improvers watch and describe how this happens. Even more clever improvers plan and actively manage the process in a way that optimises the impact of...

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Safety risks associated with the lack of integration and interfacing of hospital health information technologies: a qualitative study of hospital electronic prescribing systems in England

Background

Substantial sums of money are being invested worldwide in health information technology. Realising benefits and mitigating safety risks is however highly dependent on effective integration of information within systems and/or interfacing to allow information exchange across systems. As part of an English programme of research, we explored the social and technical challenges relating to integration and interfacing experienced by early adopter hospitals of standalone and hospital-wide multimodular integrated electronic prescribing (ePrescribing) systems.

Methods

We collected longitudinal qualitative data from six hospitals, which we conceptualised as case studies. We conducted 173 interviews with users, implementers and software suppliers (at up to three different times), 24 observations of system use and strategic meetings, 17 documents relating to implementation plans, and 2 whole-day expert round-table discussions. Data were thematically analysed initially within and then across cases, drawing on perspectives surrounding information infrastructures.

Results

We observed that integration and interfacing problems obstructed effective information transfer in both standalone and multimodular systems, resulting in threats to patient safety emerging from the lack of availability of timely information and duplicate data entry. Interfacing problems were immediately evident in some standalone systems where users had to cope with multiple log-ins, and this did not attenuate over time. Multimodular systems appeared at first sight to obviate such problems. However, with these systems, there was a perceived lack of data coherence across modules resulting in challenges in presenting a comprehensive overview of the patient record, this possibly resulting from the piecemeal implementation of modules with different functionalities. Although it was possible to access data from some primary care systems, we found poor two-way transfer of data between hospitals and primary care necessitating workarounds, which in turn led to the opportunity for new errors associated with duplicate and manual information transfer. Extending ePrescribing to include modules with other clinically important information needed to support care was still an aspiration in most sites, although some advanced multimodular systems had begun implementing this functionality. Multimodular systems were, however, seen as being difficult to interface with external systems.

Conclusions

The decision to pursue a strategy of purchasing standalone systems and then interfacing these, or one of buying hospital-wide multimodular systems, is a pivotal one for hospitals in realising the vision of achieving a fully integrated digital record, and this should be predicated on a clear appreciation of the relative trade-offs between these choices. While multimodular systems offered somewhat better usability, standalone systems provided greater flexibility and opportunity for innovation, particularly in relation to interoperability with external systems and in relation to customisability to the needs of different user groups.

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