Reporting of Sepsis Cases for Performance Measurement Versus for Reimbursement in New York State*

Objectives: Under "Rory's Regulations," New York State Article 28 acute care hospitals were mandated to implement sepsis protocols and report patient-level data. This study sought to determine how well cases reported under state mandate align with discharge records in a statewide administrative database. Design: Observational cohort study. Setting: First 27 months of mandated sepsis reporting (April 1, 2014, to June 30, 2016). Patients: Hospitalizations with sepsis at New York State Article 28 acute care hospitals. Intervention: Sepsis regulations with mandated reporting. Measurements and Main Results: We compared cases reported to the New York State Department of Health Sepsis Clinical Database with discharge records in the Statewide Planning and Research Cooperative System database. We classified discharges as 1) "coded sepsis discharges"—a diagnosis code for severe sepsis or septic shock and 2) "possible sepsis discharges," using Dombrovskiy and Angus criteria. Of 111,816 sepsis cases reported to the New York State Department of Health Sepsis Clinical Database, 105,722 (94.5%) were matched to discharge records in Statewide Planning and Research Cooperative System. The percentage of coded sepsis discharges reported increased from 67.5% in the first quarter to 81.3% in the final quarter of the study period (mean, 77.7%). Accounting for unmatched cases, as many as 82.7% of coded sepsis discharges were potentially reported, whereas at least 17.3% were unreported. Compared with unreported discharges, reported discharges had higher rates of acute organ dysfunction (e.g., cardiovascular dysfunction 63.0% vs 51.8%; p

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Is “Moderate” the Correct Adjective?*

No abstract available

https://ift.tt/2IPY5ZS

Vasopressors During Cardiopulmonary Resuscitation. A Network Meta-Analysis of Randomized Trials

Objectives: Several randomized controlled trials have compared adrenaline (epinephrine) with alternative therapies in patients with cardiac arrest with conflicting results. Recent observational studies suggest that adrenaline might increase return of spontaneous circulation but worsen neurologic outcome. We systematically compared all the vasopressors tested in randomized controlled trials in adult cardiac arrest patients in order to identify the treatment associated with the highest rate of return of spontaneous circulation, survival, and good neurologic outcome. Design: Network meta-analysis. Patients: Adult patients undergoing cardiopulmonary resuscitation. Interventions: PubMed, Embase, BioMed Central, and the Cochrane Central register were searched (up to April 1, 2017). We included all the randomized controlled trials comparing a vasopressor with any other therapy. A network meta-analysis with a frequentist approach was performed to identify the treatment associated with the highest likelihood of survival. Measurements and Main Results: Twenty-eight studies randomizing 14,848 patients in 12 treatment groups were included. Only a combined treatment with adrenaline, vasopressin, and methylprednisolone was associated with increased likelihood of return of spontaneous circulation and survival with a good neurologic outcome compared with several other comparators, including adrenaline. Adrenaline alone was not associated with any significant difference in mortality and good neurologic outcome compared with any other comparator. Conclusions: In randomized controlled trials assessing vasopressors in adults with cardiac arrest, only a combination of adrenaline, vasopressin, and methylprednisolone was associated with improved survival with a good neurologic outcome compared with any other drug or placebo, particularly in in-hospital cardiac arrest. There was no significant randomized evidence to support neither discourage the use of adrenaline during cardiac arrest.

https://ift.tt/2HqIrqu

The New York Sepsis Severity Score: Development of a Risk-Adjusted Severity Model for Sepsis

Objectives: In accordance with Rory's Regulations, hospitals across New York State developed and implemented protocols for sepsis recognition and treatment to reduce variations in evidence informed care and preventable mortality. The New York Department of Health sought to develop a risk assessment model for accurate and standardized hospital mortality comparisons of adult septic patients across institutions using case-mix adjustment. Design: Retrospective evaluation of prospectively collected data. Patients: Data from 43,204 severe sepsis and septic shock patients from 179 hospitals across New York State were evaluated. Settings: Prospective data were submitted to a database from January 1, 2015, to December 31, 2015. Interventions: None. Measurement and Main Results: Maximum likelihood logistic regression was used to estimate model coefficients used in the New York State risk model. The mortality probability was estimated using a logistic regression model. Variables to be included in the model were determined as part of the model-building process. Interactions between variables were included if they made clinical sense and if their p values were less than 0.05. Model development used a random sample of 90% of available patients and was validated using the remaining 10%. Hosmer-Lemeshow goodness of fit p values were considerably greater than 0.05, suggesting good calibration. Areas under the receiver operator curve in the developmental and validation subsets were 0.770 (95% CI, 0.765–0.775) and 0.773 (95% CI, 0.758–0.787), respectively, indicating good discrimination. Development and validation datasets had similar distributions of estimated mortality probabilities. Mortality increased with rising age, comorbidities, and lactate. Conclusions: The New York Sepsis Severity Score accurately estimated the probability of hospital mortality in severe sepsis and septic shock patients. It performed well with respect to calibration and discrimination. This sepsis-specific model provides an accurate, comprehensive method for standardized mortality comparison of adult patients with severe sepsis and septic shock.

https://ift.tt/2JLZfXp

Acute Kidney Injury and Subsequent Frailty Status in Survivors of Critical Illness: A Secondary Analysis

Objectives: Acute kidney injury frequently complicates critical illness and is associated with high morbidity and mortality. Frailty is common in critical illness survivors, but little is known about the impact of acute kidney injury. We examined the association of acute kidney injury and frailty within a year of hospital discharge in survivors of critical illness. Design: Secondary analysis of a prospective cohort study. Setting: Medical/surgical ICU of a U.S. tertiary care medical center. Patients: Three hundred seventeen participants with respiratory failure and/or shock. Interventions: None. Measurements and Main Results: Acute kidney injury was determined using Kidney Disease Improving Global Outcomes stages. Clinical frailty status was determined using the Clinical Frailty Scale at 3 and 12 months following discharge. Covariates included mean ICU Sequential Organ Failure Assessment score and Acute Physiology and Chronic Health Evaluation II score as well as baseline comorbidity (i.e., Charlson Comorbidity Index), kidney function, and Clinical Frailty Scale score. Of 317 patients, 243 (77%) had acute kidney injury and one in four patients with acute kidney injury was frail at baseline. In adjusted models, acute kidney injury stages 1, 2, and 3 were associated with higher frailty scores at 3 months (odds ratio, 1.92; 95% CI, 1.14–3.24; odds ratio, 2.40; 95% CI, 1.31–4.42; and odds ratio, 4.41; 95% CI, 2.20–8.82, respectively). At 12 months, a similar association of acute kidney injury stages 1, 2, and 3 and higher Clinical Frailty Scale score was noted (odds ratio, 1.87; 95% CI, 1.11–3.14; odds ratio, 1.81; 95% CI, 0.94–3.48; and odds ratio, 2.76; 95% CI, 1.34–5.66, respectively). In supplemental and sensitivity analyses, analogous patterns of association were observed. Conclusions: Acute kidney injury in survivors of critical illness predicted worse frailty status 3 and 12 months postdischarge. These findings have important implications on clinical decision making among acute kidney injury survivors and underscore the need to understand the drivers of frailty to improve patient-centered outcomes.

https://ift.tt/2IRjim6

Systematic Review and Meta-Analysis of Procalcitonin-Guidance Versus Usual Care for Antimicrobial Management in Critically Ill Patients: Focus on Subgroups Based on Antibiotic Initiation, Cessation, or Mixed Strategies*

Objective: Numerous studies have evaluated the use of procalcitonin guidance during different phases of antibiotics management (initiation, cessation, or a combination of both) in patients admitted to ICUs. Several meta-analyses have attempted to generate an overall effect of procalcitonin-guidance on patient outcomes. However, combining studies from different phases of antibiotics management may not be appropriate due to the risk of clinical heterogeneity. The purpose of this systematic review and meta-analysis was to evaluate the effect of procalcitonin-guided strategies in different phases of antibiotics use. Data Sources: We searched MEDLINE and EMBASE from inception until November 1, 2017. Study Selection: We included randomized controlled trials that evaluated procalcitonin guidance compared with usual care for management of antibiotics in critically ill adult patients. Data Extraction: We extracted study details, patient characteristics, procalcitonin algorithm, and outcomes. Data Synthesis: We included 15 studies, from 1,624 abstracts identified based on our search strategy (three initiation, nine cessation, and three mixed). The pooled risk ratio for short-term mortality for the initiation, cessation, and mixed procalcitonin strategies were 1.00 (95% CI, 0.86–1.15,;p = 0.91), 0.87 (95% CI, 0.77–0.98; p = 0.02), and 1.01 (95% CI, 0.80–1.29; p = 0.93), respectively. Procalcitonin for cessation and mixed strategies was associated with decrease antibiotics duration (–1.26 d [p

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Integration of an Abbreviated ICU Cognitive Failure Questionnaire

No abstract available

https://ift.tt/2qvht7v

Efficacy and Safety of Procalcitonin Guidance in Patients With Suspected or Confirmed Sepsis: A Systematic Review and Meta-Analysis*

Objective: Sepsis is a leading cause of mortality in noncoronary ICUs. Although immediate start of antibiotics reduces sepsis-related mortality, antibiotics are often administered for too long, leading to suboptimal treatment and, importantly, contributes to antimicrobial resistance. Prior literature suggests that procalcitonin correlates with infection and thus may help to guide the decision on when to stop antibiotic treatment. This study was conducted as part of a regulatory submission to the U.S. Food and Drug Administration and aimed to summarize the evidence of procalcitonin guidance on efficacy and safety outcomes in adult patients with sepsis. Data Sources: PubMed and the Cochrane Database of Systematic Reviews. Study Selection: English-language randomized controlled trials evaluating procalcitonin use among adult patients with suspected or confirmed sepsis published between January 2004 and May 2016. Data Extraction: Inverse-variance weighting fixed and random effects meta-analyses were performed on the following efficacy and safety endpoints: antibiotic duration, all-cause mortality, and length of ICU stay. Two reviewers independently extracted data elements from identified studies and measured risk of bias with the Cochrane Risk of Bias Tool. Data Synthesis: From a total of 369 potentially eligible articles, 10 randomized controlled trials containing 3,489 patients were used for analysis. Procalcitonin-guided patients had shorter antibiotics duration compared with controls (7.35 vs. 8.85 d; weighted mean difference, –1.49 d; 95% CI, –2.27 to –0.71; p

https://ift.tt/2JJDBmw

Long-Term Cognitive Outcome and Brain Imaging in Adults After Extracorporeal Membrane Oxygenation

Objectives: To investigate the presence of cognitive dysfunction and brain lesions in long-term survivors after treatment with extracorporeal membrane oxygenation for severe respiratory failure, and to see whether patients with prolonged hypoxemia were at increased risk. Design: A single-center retrospective cohort study. Setting: Tertiary referral center for extracorporeal membrane oxygenation in Sweden. Patients: Long-term survivors treated between 1995 and July 2009. Seven patients from a previously published study investigated with a similar protocol were included. Interventions: Brain imaging, neurocognitive testing, interview. Measurements and Main Results: Thirty-eight patients (i.e., n = 31 + 7) were enrolled and investigated in median 9.0 years after discharge. Only memory tests were performed in 10 patients, mainly due to a lack of formal education necessary for the test results to be reliable. Median full-scale intelligence quotient, memory index, and executive index were 97, 101, and 104, respectively (normal, 100 ± 15). Cognitive function was not reduced in the group with prolonged hypoxemia. Brain imaging showed cerebrovascular lesions in 14 of 38 patients (37%), most commonly in the group treated with venoarterial extracorporeal membrane oxygenation (7/11, 64%). In this group, memory function and executive function were significantly reduced. Conclusions: Patients treated with extracorporeal membrane oxygenation for respiratory failure may have normal cognitive function years after treatment, if not affected by cerebrovascular lesions. Permissive hypoxemia was not correlated with long-term cognitive dysfunction in the present study. Further prospective studies with minimal loss to follow-up are direly needed to confirm our findings.

https://ift.tt/2ISP2ah

How Surrogate Decision-Makers for Patients With Chronic Critical Illness Perceive and Carry Out Their Role

Objectives: Family members commonly make medical decision for patients with chronic critical illness. This study examines how family members approach this decision-making role in real time. Design: Qualitative analysis of interviews with family members in the intervention arm of a randomized controlled communication trial. Settings: Medical ICUs at four U.S. hospitals. Participants: Family members of patients with chronic critical illness (adults mechanically ventilated for ≥ 7 d and expected to remain ventilated and survive for ≥ 72 hr) who participated in the active arm of a communication intervention study. Interventions: Family members participated in at least two content-guided, informational, and emotional support meetings led by a palliative care physician and nurse practitioner. Measurements and Main Results: Grounded theory was used for qualitative analysis of 66 audio recordings of meetings with 51 family members. Family members perceived their role in four main ways: voice of the patient, advocate for the patient, advocate for others, and advocate for oneself. Their decision-making was characterized by balancing goals, sharing their role, keeping perspective, remembering previous experiences, finding sources of strength, and coping with various burdens. Conclusions: Family members take a multifaceted approach as they participate in decision-making. Understanding how surrogates perceive and act in their roles may facilitate shared decision-making among clinicians and families during critical care.

https://ift.tt/2vbsBLw

The Five-Year Clinical and Angiographic Follow-Up Outcomes of Intracoronary Transfusion of Circulation-Derived CD34+ Cells for Patients With End-Stage Diffuse Coronary Artery Disease Unsuitable for Coronary Intervention—Phase I Clinical Trial

Objectives: This study investigated the clinical and angiographic long-term outcomes of intracoronary transfusion of circulation-derived CD34+ cells for patients with end-stage diffuse coronary artery disease unsuitable for coronary intervention. Design and Setting: A single-center prospective randomized double-blinded phase I clinical trial. Thirty-eight patients undergoing CD34+ cell therapy were allocated into groups 1 (1.0 × 107 cells/each vessel; n = 18) and 2 (3.0 × 107 cells/each vessel; n = 20). Patients: Those with end-stage diffuse coronary artery disease were unsuitable for percutaneous and surgical coronary revascularization. Interventions: Intracoronary delivery of circulation-derived CD34+ cells. Measurements and Main Results: We prospectively evaluated long-term clinical and echocardiographic/angiographic outcomes between survivors and nonsurvivors. By the end of 5-year follow-up, the survival rate and major adverse cardio/cerebrovascular event were 78.9% (30/38) and 36.8% (14/38), respectively. During follow-up period, 31.6% patients (12/38) received coronary stenting for reason of sufficient target vessel size grown-up after the treatment. Endothelial function was significantly reduced in the nonsurvivors than the survivors (p = 0.039). Wimasis image analysis of angiographic findings showed that the angiogenesis was significantly and progressively increased from baseline to 1 and 5 years (all p

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Incidence and Outcomes for Patients With Cirrhosis Admitted to the United Kingdom Critical Care Units*

Objective: To assess the epidemiology and outcome of patients with cirrhosis following critical care unit admission. Design: Retrospective cohort study. Setting: Critical care units in England, Wales, and Northern Ireland participating in the U.K. Intensive Care National Audit and Research Centre Case Mix Programme. Patients: Thirty-one thousand three hundred sixty-three patients with cirrhosis identified of 1,168,650 total critical care unit admissions (2.7%) admitted to U.K. critical care units between 1998 and 2012. Interventions: None. Measurements and Main Results: Ten thousand nine hundred thirty-six patients had alcohol-related liver disease (35%). In total, 1.6% of critical care unit admissions in 1998 had cirrhosis rising to 3.1% in 2012. The crude critical care unit mortality of patients with cirrhosis was 41% in 1998 falling to 31% in 2012 (p

https://ift.tt/2JJhpcp

Systemic Administration of Carbon Monoxide–Releasing Molecule-3 Protects the Skeletal Muscle in Porcine Model of Compartment Syndrome

Objectives: Acute limb compartment syndrome, a complication of musculoskeletal trauma, results in muscle necrosis and cell death. Carbon monoxide, liberated from the carbon monoxide–releasing molecule-3, has been shown protective in a rat model of compartment syndrome. The purpose of this study was to test the effect of carbon monoxide–releasing molecule-3 in a preclinical large animal model of compartment syndrome, with the ultimate goal of developing a pharmacologic adjunct treatment for compartment syndrome. Design: Animal research study. Setting: Basic research laboratory in a hospital setting. Subjects: Male Yorkshire-Landrace pigs (50–60 kg). Interventions: Pigs underwent 6 hours of intracompartmental pressure elevation by infusing fluid into the anterior compartment of the right hind limb. Carbon monoxide–releasing molecule-3 was administered systemically (2 mg/kg, IV) at fasciotomy, followed by 3-hour reperfusion. Measurements and Main Results: Muscle perfusion, inflammation, injury, and apoptosis were assessed in the skeletal muscle. Systemic leukocyte activation was assessed during compartment syndrome and reperfusion. Elevation of hind limb intracompartmental pressure resulted in significant microvascular perfusion deficits (44% ± 1% continuously perfused capillaries in compartment syndrome vs 76% ± 4% in sham; p

https://ift.tt/2IPJQUP

Early Risk and Resiliency Factors Predict Chronic Posttraumatic Stress Disorder in Caregivers of Patients Admitted to a Neuroscience ICU

Objectives: Informal caregivers—that is, close family and friends providing unpaid emotional or instrumental care—of patients admitted to ICUs are at risk for posttraumatic stress disorder. As a first step toward developing interventions to prevent posttraumatic stress disorder in ICU caregivers, we examined the predictive validity of psychosocial risk screening during admission for caregiver posttraumatic stress disorder at 3 and 6 months post hospitalization. Design: An observational, prospective study. Participants: Ninety-nine caregivers were recruited as part of a longitudinal research program of patient-caregiver dyads in a neuroscience ICU. Intervention: None. Measurements and Main Results: Caregiver posttraumatic stress disorder symptoms were assessed during admission (baseline), 3 months, and 6 months post hospitalization. We 1) characterized prevalence of clinically significant symptoms at each time point 2); calculated sensitivity and specificity of baseline posttraumatic stress disorder screening in predicting posttraumatic stress disorder at 3 and 6 months; and 3) used recursive partitioning to select potential baseline factors and examine the extent to which they helped predict clinically significant posttraumatic stress disorder symptoms at each time point. Rates of caregiver posttraumatic stress disorder remained relatively stable over time (16–22%). Screening for posttraumatic stress disorder at baseline predicted posttraumatic stress disorder at 3 and 6 months with moderate sensitivity (75–80%) and high specificity (92–95%). Screening for posttraumatic stress disorder at baseline was associated with caregiver anxiety, mindfulness (i.e., ability to be aware of one's thoughts and feelings in the moment), and bond with patient. Furthermore, baseline posttraumatic stress disorder screening was the single most relevant predictor of posttraumatic stress disorder at 3 and 6 months, such that other baseline factors did not significantly improve predictive ability. Conclusions: Screening neuroscience ICU caregivers for clinically significant posttraumatic stress disorder symptoms during admission is the single most important way to identify the majority of those likely to suffer from chronic posttraumatic stress disorder following discharge. Addressing early posttraumatic stress disorder symptoms and their psychosocial correlates during admission may help prevent chronic posttraumatic stress disorder in these at-risk caregivers.

https://ift.tt/2vbsy2i

“Size Matters” in Regard to Acute Respiratory Distress Syndrome Case Volume and Mortality!*

No abstract available

https://ift.tt/2vkF2VJ

Effect of Emergency Department and ICU Occupancy on Admission Decisions and Outcomes for Critically Ill Patients*

Objectives: ICU admission delays can negatively affect patient outcomes, but emergency department volume and boarding times may also affect these decisions and associated patient outcomes. We sought to investigate the effect of emergency department and ICU capacity strain on ICU admission decisions and to examine the effect of emergency department boarding time of critically ill patients on in-hospital mortality. Design: A retrospective cohort study. Setting: Single academic tertiary care hospital. Patients: Adult critically ill emergency department patients for whom a consult for medical ICU admission was requested, over a 21-month period. Interventions: None. Measurements and Main Results: Patient data, including severity of illness (Mortality Probability Model III on Admission), outcomes of mortality and persistent organ dysfunction, and hourly census reports for the emergency department, for all ICUs and all adult wards were compiled. A total of 854 emergency department requests for ICU admission were logged, with 455 (53.3%) as "accept" and 399 (46.7%) as "deny" cases, with median emergency department boarding times 4.2 hours (interquartile range, 2.8–6.3 hr) and 11.7 hours (3.2–20.3 hr) and similar rates of persistent organ dysfunction and/or death 41.5% and 44.6%, respectively. Those accepted were younger (mean ± SD, 61 ± 17 vs 65 ± 18 yr) and more severely ill (median Mortality Probability Model III on Admission score, 15.3% [7.0–29.5%] vs 13.4% [6.3–25.2%]) than those denied admission. In the multivariable model, a full medical ICU was the only hospital-level factor significantly associated with a lower probability of ICU acceptance (odds ratio, 0.55 [95% CI, 0.37–0.81]). Using propensity score analysis to account for imbalances in baseline characteristics between those accepted or denied for ICU admission, longer emergency department boarding time after consult was associated with higher odds of mortality and persistent organ dysfunction (odds ratio, 1.77 [1.07–2.95]/log10 hour increase). Conclusions: ICU admission decisions for critically ill emergency department patients are affected by medical ICU bed availability, though higher emergency department volume and other ICU occupancy did not play a role. Prolonged emergency department boarding times were associated with worse patient outcomes, suggesting a need for improved throughput and targeted care for patients awaiting ICU admission.

https://ift.tt/2JKYwFS

Time for Targeted Therapies in Acute Respiratory Distress Syndrome? Understanding Every Single Piece of the Puzzle*

No abstract available

https://ift.tt/2HhX13E

Impact of Telemedicine on Mortality, Length of Stay, and Cost Among Patients in Progressive Care Units: Experience From a Large Healthcare System*

Objectives: To determine whether Telemedicine intervention can affect hospital mortality, length of stay, and direct costs for progressive care unit patients. Design: Retrospective observational. Setting: Large healthcare system in Florida. Patients: Adult patients admitted to progressive care unit (PCU) as their primary admission between December 2011 and August 2016 (n = 16,091). Interventions: Progressive care unit patients with telemedicine intervention (telemedicine PCU [TPCU]; n = 8091) and without telemedicine control (nontelemedicine PCU [NTPCU]; n = 8000) were compared concurrently during study period. Measurements and Main Results: Primary outcome was progressive care unit and hospital mortality. Secondary outcomes were hospital length of stay, progressive care unit length of stay, and mean direct costs. The mean age NTPCU and TPCU patients were 63.4 years (95% CI, 62.9–63.8 yr) and 71.1 years (95% CI, 70.7–71.4 yr), respectively. All Patient Refined-Diagnosis Related Group Disease Severity (p

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Is Heparin-Binding Protein Inhibition a Mechanism of Albumin’s Efficacy in Human Septic Shock?

Objectives: Our objectives were to determine first whether albumin prevents heparin-binding protein–induced increased endothelial cell permeability and renal cell inflammation and second, whether a plasma heparin-binding protein-to-albumin ratio predicts risk of acute kidney injury, fluid balance, and plasma cytokine levels in septic shock. Design: In vitro human endothelial and renal cell model and observation cohort of septic shock. Settings: Research laboratory and multicenter clinical trial (Vasopressin and Septic Shock Trial). Patients: Adult septic shock (norepinephrine dose > 5 μg/min for > 6 hr). Interventions: In vitro: heparin-binding protein (or thrombin) was added with or without albumin to 1) human endothelial cell monolayers to assess permeability and 2) to human renal tubular epithelial cells to assess inflammation. Measurements and Main Results: Transendothelial electrical resistance—a marker of permeability—of human endothelial cells was measured using a voltohmmeter. We measured plasma heparin-binding protein-to-albumin ratio and a panel of cytokines in septic shock patients (n = 330) to define an heparin-binding protein-to-albumin ratio that predicts risk of acute kidney injury. Albumin inhibited heparin-binding protein (and thrombin-induced) increased endothelial cell permeability at a threshold concentration of 20–30 g/L but increased renal tubular cell interleukin-6 release. Patients who developed or had worsened acute kidney injury had significantly higher heparin-binding protein-to-albumin ratio (1.6 vs 0.89; p 3.05), heparin-binding protein quartiles (> 69.8), and heparin-binding protein > 30 ng/mL were significantly associated with development or worsening of acute kidney injury (p

https://ift.tt/2ITnRMD

Sepsis-Associated Coagulopathy Severity Predicts Hospital Mortality*

Objectives: To assess whether sepsis-associated coagulopathy predicts hospital mortality. Design: Retrospective cohort study. Setting: One-thousand three-hundred beds urban academic medical center. Patients: Six-thousand one-hundred forty-eight consecutive patients hospitalized between January 1, 2010, and December 31, 2015. Interventions: Mild sepsis-associated coagulopathy was defined as an international normalized ratio greater than or equal to 1.2 and less than 1.4 plus platelet count less than or equal to 150,000/µL but greater than 100,000/µL; moderate sepsis-associated coagulopathy was defined with either an international normalized ratio greater than or equal to 1.4 but less than 1.6 or platelets less than or equal to 100,000/µL but greater than 80,000/µL; severe sepsis-associated coagulopathy was defined as an international normalized ratio greater than or equal to 1.6 and platelets less than or equal to 80,000/µL. Measurements and Main Results: Hospital mortality increased progressively from 25.4% in patients without sepsis-associated coagulopathy to 56.1% in patients with severe sepsis-associated coagulopathy. Similarly, duration of hospitalization and ICU care increased progressively as sepsis-associated coagulopathy severity increased. Multivariable analyses showed that the presence of sepsis-associated coagulopathy, as well as sepsis-associated coagulopathy severity, was independently associated with hospital mortality regardless of adjustments made for baseline patient characteristics, hospitalization variables, and the sepsis-associated coagulopathy-cancer interaction. Odds ratios ranged from 1.33 to 2.14 for the presence of sepsis-associated coagulopathy and from 1.18 to 1.51 for sepsis-associated coagulopathy severity for predicting hospital mortality (p

https://ift.tt/2JKYw8Q

Updates on antibody functions in Mycobacterium tuberculosis infection and their relevance for developing a vaccine against tuberculosis

Jacqueline M Achkar | Rafael Prados-Rosales

https://ift.tt/2GWKxz9

Larotrectinib Has Antitumor Activity in TRK+ Pediatric Solid Tumors [Research Watch]

Larotrectinib achieved a 93% response rate in pediatric patients with TRK fusion–positive tumors.

https://ift.tt/2v8Exxy

The IL15 Superagonist ALT-803 plus Nivolumab Has Antitumor Activity [Research Watch]

Nivolumab in combination with ALT-803 is tolerable and achieves responses in patients with NSCLC.

https://ift.tt/2JIayA0

SLAM-seq Identifies Direct Transcriptional Targets of BRD4 and MYC [Research Watch]

BRD4 activates RNA Pol2–dependent transcription, whereas MYC activates a confined set of target genes.

https://ift.tt/2viytms

Mechanisms of Oncogene-Induced Replication Stress: Jigsaw Falling into Place [Review]

Oncogene activation disturbs cellular processes and accommodates a complex landscape of changes in the genome that contribute to genomic instability, which accelerates mutation rates and promotes tumorigenesis. Part of this cellular turmoil involves deregulation of physiologic DNA replication, widely described as replication stress. Oncogene-induced replication stress is an early driver of genomic instability and is attributed to a plethora of factors, most notably aberrant origin firing, replication–transcription collisions, reactive oxygen species, and defective nucleotide metabolism.

Significance: Replication stress is a fundamental step and an early driver of tumorigenesis and has been associated with many activated oncogenes. Deciphering the mechanisms that contribute to the replication stress response may provide new avenues for targeted cancer treatment. In this review, we discuss the latest findings on the DNA replication stress response and examine the various mechanisms through which activated oncogenes induce replication stress. Cancer Discov; 8(5); 1–19. ©2018 AACR.

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Glioblastoma Stem Cell-Tumor Cell Cross-talk Drives Gliomagenesis [Research Watch]

Reciprocal paracrine signaling between GBM stem cells and GBM cells promotes tumor growth.

https://ift.tt/2EKI7xz

Coastal Meds to Recall All Products Marketed as Sterile

[Posted 04/13/2018] AUDIENCE: Pharmacy, Nursing, Risk Manager  ISSUE: FDA is alerting health care professionals to a voluntary recall of all non-expired products marketed as sterile made by Coastal Meds due to visible particles in some of the...

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Resistance to Antibody-Drug Conȷugates

Antibody–drug conjugates (ADC) are multicomponent molecules constituted by an antibody covalently linked to a potent cytotoxic agent. ADCs combine high target specificity provided by the antibody together with strong antitumoral properties provided by the attached cytotoxic agent. At present, four ADCs have been approved and over 60 are being explored in clinical trials. Despite their effectiveness, resistance to these drugs unfortunately occurs. Efforts to understand the bases underlying such resistance are being carried out with the final purpose of counteracting them. In this review, we report described mechanisms of resistance to ADCs used in the clinic along with other potential ones that may contribute to resistance acquisition. We also discuss strategies to overcome resistance to ADCs. Cancer Res; 1–7. ©2018 AACR.

https://ift.tt/2JJ4F5v

Mitotic Exit dysfunction through the deregulation of APC/C characterizes cisplatin resistant state in epithelial ovarian cancer

Purpose: Acquired resistance to cisplatin is a major barrier to success in treatment of various cancers and understanding mitotic mechanisms unique to cisplatin resistant cancer cells can provide the basis for developing novel mitotic targeted therapies aimed at eradicating these cells. Experimental Design: Using cisplatin resistant models derived from primary patient epithelial ovarian cancer (EOC) cells, we have explored the status of mitotic exit mechanisms in cisplatin resistant cells. Results: We have uncovered an unexpected role of long-term cisplatin treatment in inducing mitotic exit vulnerability characterized by increased spindle checkpoint activity and functional dependency on Polo-like kinase 1 (PLK1) for mitotic exit in the presence of Anaphase Promoting Complex/Cyclosome (APC/C) dysfunction in a cisplatin resistant state. Accordingly, PLK1 inhibition decreased the survival of cisplatin resistant cells in-vitro and in-vivo, and exacerbated spindle checkpoint response in these cells. APC/C ^CDC20 inhibition increased sensitivity to pharmacologic PLK1 inhibition further confirming the existence of APC/C dysfunction cisplatin resistant cells. In addition, we uncovered that resistance to Volasertib, PLK1 inhibitor, is due to maintenance of cells with low PLK1 expression. Accordingly, stable PLK1 downregulation in cisplatin resistant cells induced tolerance to Volasertib. Conclusions: We provide the first evidence of APC/C dysfunction in cisplatin resistant state, suggesting that understanding APC/C functions in cisplatin resistant state could provide basis for developing novel mitotic exit based therapies to eradicate cisplatin resistant cancer cells. Our results also show that PLK1 down-regulation could underlie emergence of resistance to PLK1 targeted therapies in cancers.

https://ift.tt/2IS8jIZ

The Atypical Rho GTPase CHW-1 Works with SAX-3/Robo To Mediate Axon Guidance in Caenorhabditis elegans

During development, neuronal cells extend an axon towards their target destination in response to a cue to form a properly functioning nervous system. Rho proteins, Ras-related small GTPases that regulate cytoskeletal organization and dynamics, cell adhesion, and motility, are known to regulate axon guidance. Despite extensive knowledge about canonical Rho proteins (RhoA/Rac1/Cdc42), little is known about the Caenorhabditis elegans (C. elegans) atypical Cdc42-like family members CHW-1 and CRP-1 in regards to axon pathfinding and neuronal migration. chw-1 (Chp/Wrch) encodes a protein that resembles human Chp (Wrch-2/RhoV) and Wrch-1 (RhoU), and crp-1 encodes for a protein that resembles TC10 and TCL. Here, we show that chw-1 works redundantly with crp-1 and cdc-42 in axon guidance. Furthermore, proper levels of chw-1 expression and activity are required for proper axon guidance. When examining CHW-1 GTPase mutants, we found that the native CHW-1 protein is likely partially activated, and mutations at a conserved residue (position 12 using Ras numbering, position 18 in CHW-1) alter axon guidance and neural migration. Additionally, we showed that chw-1 genetically interacts with the guidance receptor sax-3 in PDE neurons. Finally, in VD/DD motor neurons, chw-1 works downstream of sax-3 to control axon guidance. In summary, this is the first study implicating the atypical Rho GTPases chw-1 and crp-1 in axon guidance. Furthermore, this is the first evidence of genetic interaction between chw-1 and the guidance receptor sax-3. These data suggest that chw-1 is likely acting downstream and/or in parallel to sax-3 in axon guidance.

https://ift.tt/2qAK1fl

Negative Affect That Lingers Tied to Health 10 Years Later

FRIDAY, April 13, 2018 -- Negative affect that lingers is associated with worse physical health outcomes almost 10 years later, according to a study published online March 19 in Psychological Science. Kate A. Leger, Ph.D., from the University of...

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n-3 Fatty Acids Don't Seem to Be of Any Benefit in Dry Eye Disease

FRIDAY, April 13, 2018 -- Supplementation with n-3 fatty acids is not associated with significant benefit in dry eye disease, according to a study published online April 13 in the New England Journal of Medicine to coincide with the annual meeting...

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Yoga, Mindfulness Aid Anxiety in Elementary School Children

FRIDAY, April 13, 2018 -- Classroom-based yoga and mindfulness activities may be effective tools for stress management among elementary school students, according to a study published online April 10 in Psychology Research and Behavior...

https://ift.tt/2IR7vUS

FDA Approves AI Device to Detect Diabetic Retinopathy

FRIDAY, April 13, 2018 -- Artificial intelligence software that can detect diabetic retinopathy has been approved by the U.S. Food and Drug Administration. The IDx-DR program analyzes images of a patient's retinas taken with a special camera. The...

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FDA Cracks Down on Caffeine-Loaded Dietary Supplements

FRIDAY, April 13, 2018 -- The U.S. Food and Drug Administration announced Friday that it has issued tough new restrictions on the sale of dietary supplements that contain dangerously high amounts of caffeine. Supplements that contain pure or highly...

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Coastal Meds to Recall All Products Marketed as Sterile

[Posted 04/13/2018] AUDIENCE: Pharmacy, Nursing, Risk Manager  ISSUE: FDA is alerting health care professionals to a voluntary recall of all non-expired products marketed as sterile made by Coastal Meds due to visible particles in some of the...

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The Association Between Mutations in BRAF and Colorectal Cancer-specific Survival Depends on Microsatellite Status and Tumor Stage

Colorectal tumors with mutations in BRAF and microsatellite stability (MSS) have been associated with adverse outcomes of patients. Combined tests for microsatellite instability (MSI-H) and BRAF mutations might therefore be used in risk assessment, particularly for patients with stage II tumors. We investigate the stage-specific prognostic value of combined testing for MSI-H and BRAF for patients with colorectal cancer (CRC).

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Duodenal Scalloping Diagnoses Waldenström Macroglobulinemia

https://ift.tt/2IU43ZD

Gastric PerOral Endoscopic Pyloromyotomy Reduces Symptoms, Increases Quality of Life, and Reduces Healthcare Usage For Patients With Gastroparesis*

Gastric per-oral endoscopic pyloromyotomy (GPOEM) is becoming a promising treatment option for patients with refractory gastroparesis. We aimed to systematically assess the efficacy of GPOEM and its effects on healthcare usage.

https://ift.tt/2HlOBIp

Yield of Colonoscopy After a Positive Result From a Fecal Immunochemical Test OC-Light

The fecal immunochemical test (FIT) is widely used in colorectal cancer (CRC) screening. The OC-Light FIT is 1 of 2 FITs recommended for CRC screening by the Preventive Services Task Force guidelines. However, little is known about its ability to detect CRC in large average-risk populations.

https://ift.tt/2IVdCr1

Water-pocket endoscopic submucosal dissection for superficial gastric neoplasms (with video)

During endoscopic submucosal dissection (ESD), a clear view is essential for precise dissection of the appropriate submucosal layer. Some advantages have been reported for underwater techniques of endoscopic resection in comparison with the gas insufflation method. We have developed a new ESD method with the creation of a local water-pocket that provides a clear view in the dissection field. Therefore, we aimed to investigate the feasibility and safety of water-pocket ESD (WP-ESD) for superficial gastric neoplasms.

https://ift.tt/2EK1JSq

Reliability among central readers in the evaluation of endoscopic disease activity in pouchitis

Pouchitis is a common adverse event after proctocolectomy with ileal pouch anal anastomosis for ulcerative colitis. Evaluation of pouchitis disease activity and response to treatment requires use of validated indices. We assessed the reliability of items evaluating endoscopic pouchitis disease activity.

https://ift.tt/2JL37YM

Efficacy and safety of endobiliary radiofrequency ablation for the eradication of residual neoplasia after endoscopic papillectomy : a multicenter prospective study

and study aims: Endobiliary dysplasia may persist after endoscopic papillectomy. Intraductal radiofrequency ablation (ID-RFA) is a potential alternative to complementary surgery. The aim of the study was to evaluate the efficacy and safety of ID-RFA for the treatment of adenomatous intraductal residue after endoscopic papillectomy.

https://ift.tt/2EJVrCc

A Review of Real-Time 3D IGRT on Standard-Equipped Cancer Radiotherapy Systems: Are We at the Tipping Point for the Era of Real-Time Radiotherapy?

Until now, real-time 3D image guided radiotherapy (IGRT) has been the domain of dedicated cancer radiotherapy systems. However, the tipping point to the broad adoption of real-time IGRT is the availability of this technology on standard-equipped radiotherapy systems. The purpose of this work is to review real-time 3D IGRT on standard-equipped cancer radiotherapy systems, focusing on clinically implemented solutions.

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RECORDS: improved Reporting of montE CarlO RaDiation transport Studies

https://ift.tt/2quVddX

The Correlation of Regional Lung Ventilation and Gas Transfer to Red Blood Cells: Implications for Functional-Avoidance Radiation Therapy Planning

Functionally-guided radiation therapy (RT) planning using 4-Dimensional Computed Tomography (4DCT)-derived ventilation is gaining momentum. However, an important question remains: is regional lung ventilation a good surrogate for end-to-end lung function, i.e., gas transfer to Red Blood Cells (RBCs). We acquired functional image data for N=17 human subjects, using state-of-the-art hyperpolarized (HP)-129Xe Magnetic Resonance Imaging (MRI). We analyzed the correlation of ventilation and RBC transfer, and calculated the similarity of planning optimization structures created from each.

https://ift.tt/2vcgzlh

Dynamic contrast-enhanced magnetic resonance imaging for differentiating osteomyelitis from acute neuropathic arthropathy in the complicated diabetic foot

Abstract

Objective

The main purpose of this study was to investigate the diagnostic value of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating osteomyelitis from acute neuropathic arthropathy in the diabetic foot.

Materials and Methods

This prospective study was carried out on 30 diabetic foot patients, with a mean age of 51 years. The patients all underwent clinical examinations, laboratory examinations and DCE-MRI. The DCE-MRI parameters (K^trans, K_ep and V_e) of the regions of acute neuropathic arthropathy and osteomyelitis were calculated. Receiver operating characteristic curves (ROCs) were used to identify the DCE-MRI parameters that showed the highest accuracy in differentiating the acute neuropathic arthropathy from the osteomyelitic regions. Pearson correlation coefficients were used to assess the correlations among the DCE-MRI parameters, the level of C-reactive protein (CRP) and the erythrocyte sedimentation rate (ESR).

Results

The K^trans, K_ep and V_e values of the osteomyelitic regions were higher than those of the acute neuropathic arthropathy regions, and significant differences were found between the two groups (P = 0.000, P = 0.000, P = 0.000). The ROC analysis showed that K^trans and V_e performed best in differentiating osteomyelitis from acute neuropathic arthropathy, both with an area under the curve of 0.938. The Pearson correlation coefficients showed that the DCE-MRI parameters correlated significantly with the level of CRP and ESR (P = 0.000, P = 0.014, P = 0.000; P = 0.000, P = 0.000, P = 0.013).

Conclusions

Our results showed that DCE-MRI may provide reproducible parameters that can reliably differentiate osteomyelitis from acute neuropathic arthropathy.

https://ift.tt/2Hl3wCM

Initial Metabolic Profiles Are Associated with 7-Day Survival among Infants Born at 22-25 Weeks of Gestation

To evaluate the association between early metabolic profiles combined with infant characteristics and survival past 7 days of age in infants born at 22-25 weeks of gestation.

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Clinically Actionable Hypercholesterolemia and Hypertriglyceridemia in Children with Nonalcoholic Fatty Liver Disease

To determine the percentage of children with nonalcoholic fatty liver disease (NAFLD) in whom intervention for low-density lipoprotein cholesterol or triglycerides was indicated based on National Heart, Lung, and Blood Institute guidelines.

https://ift.tt/2vbIZvD

Observational Prospective Natural History of Patients with Sanfilippo Syndrome Type B

To evaluate the natural course of disease progression in patients with Sanfilippo syndrome type B (mucopolysaccharidosis type IIIB), identify potential end points for future therapy trials, and characterize biomarkers related to the disease.

https://ift.tt/2HkJhVJ

CKD and ESRD in US Hispanics

Hispanics are the largest racial/ethnic minority group in the United States, and they experience a substantial burden of kidney disease. Although the prevalence of chronic kidney disease (CKD) is similar or slightly lower in Hispanics than non-Hispanic whites, the age- and sex-adjusted prevalence rate of end-stage renal disease is almost 50% higher in Hispanics compared with non-Hispanic whites. This has been attributed in part to faster CKD progression among Hispanics. Furthermore, Hispanic ethnicity has been associated with a greater prevalence of cardiovascular disease risk factors, including obesity and diabetes, as well as CKD-related complications.

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Helping Patients With ESRD and Earlier Stages of CKD to Quit Smoking

Among the many adverse effects of tobacco exposure is the increased risk for progression of kidney disease. Individuals with chronic kidney disease (CKD), who already face increased cardiovascular event rates compared to the general population, are at even greater risk if they smoke. Despite these risks and the increased focus on smoking cessation in the general population in recent years, national guidelines have not specifically targeted individuals with CKD. There are similarly sparse data specific to individuals with CKD regarding the safety and efficacy of evidence-based smoking cessation modalities.

https://ift.tt/2IV2Z7V

Protein Digestion, Ultrafiltration, and Size Exclusion Chromatography to Optimize the Isolation of Exosomes from Human Blood Plasma and Serum

Here, we present a protocol to purify exosomes from both plasma and serum with reduced co-purification of non-exosomal blood proteins. The optimized protocol includes ultrafiltration, protease treatment, and size exclusion chromatography. Enhanced purification of exosomes benefits downstream analyses, including more accurate quantification of vesicles and proteomic characterization.

https://ift.tt/2GYe9bf

Severe perineal lacerations after vaginal delivery: are they an anesthesiologist's problem?

Purpose of review Perineal tears or lacerations are common occurrences after vaginal delivery. Understanding the degree of severity of these tears and the immediate and long-term complications of severe perineal lacerations can assist anesthesiologists with the management of these patients in the immediate postpartum period. Recent findings Severe perineal lacerations have a high degree of association with postpartum depression. The presence of neuraxial labor analgesia decreases the odds of severe perineal lacerations. Summary Neuraxial labor analgesia does not directly predispose parturients to the development of perineal lacerations, and may even be protective against these injuries. Correspondence to Feyce Peralta, MD, 251 E. Huron St. F5-704, Chicago, IL 60611, USA. Tel: +1 312 472 3585; e-mail: feyce.peralta@northwestern.edu Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Clinical pearls part 3: anaesthetic management of abnormally invasive placentation

Purpose of review Abnormal placentation is a clinical condition seen increasingly in the pregnant population. It is associated with significant morbidity and mortality, which may be mitigated through robust multidisciplinary care for these patients. The role of maternal critical care for these patients has largely been ignored in the literature. Recent findings Advances in pharmacological management of bleeding with recent publications of large multicentre trials in addition to new technologies in the management of massive obstetric haemorrhage (MOH) have revolutionized the management of abnormal placentation. These include the use of tranexamic acid, interventional radiology, cell saver technology, and point-of-care coagulation tests. The role of maternal critical care for the optimization of postoperative complications and physiological derangements has not been considered widely in the literature. This article summarizes the current evidence for interventions and suggests a protocol for the management of these high-risk patients. Summary A robust protocol outlining the key elements of the management of placenta accreta, including optimizing postoperative care, should be in place to promote desired outcomes. Correspondence to Dr Vinod Patil, Consultant Obstetric Anaesthetist, Department of Anesthesiology, Queens Hospital, BHR University Hospital NHS Trust Romford, Romford RM7 0AG, UK. Tel: 44 1708503727; e-mail: Vinodpatiluk@gmail.com Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Inequalities in dental health are most evident in young children

Inequalities in dental health are most evident in 3 to 6-year-old children, according to new research. Preschoolers in socioeconomically disadvantaged families had a more than four times higher risk of tooth decay compared to age cohorts with better living conditions.

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Deep Vein Thrombosis Induced by Stasis in Mice Monitored by High Frequency Ultrasonography

The present protocol describes the steps to obtain venous thrombosis using a stasis model. In addition, we are using a non-invasive method to measure thrombus formation and resolution over time.

https://ift.tt/2GZPof3

Assessing Lysosomal Alkalinization in the Intestine of Live Caenorhabditis elegans

A step-by-step guide to probe loss of lysosomal acidity in the intestine of C. elegans using the pH-sensitive vital dye 5(6)-carboxy-2',7'-dichlorofluorescein diacetate (cDCFDA)

https://ift.tt/2HAN1jy

Ententionality and Pertinence: Framing End-Directedness within Two Semiotic Theories

Abstract

The purpose of this paper is to present a possible theoretical articulation between Terrence Deacon's concept of ententionality and the concept of pertinence as posed by semio-linguist Luis J. Prieto. The advantage of such articulation is that it brings together two seemingly incompatible approaches within semiotics, namely the Peircean and the Saussurean ones. We start by subscribing to the definition of semiotics as the study of forms of knowledge in order to highlight the importance of analyzing intentional phenomena as semiosic phenomena. Afterwards, we present the concept of ententionality and the levels of organization (homeodynamics, morphodynamics and teleodynamics) that ultimately set the conditions for entention to emerge. Then, we present an analysis of this concept aided by Prieto's notion of pertinence. Our main conclusion is that ententionality and teleodynamic organization presupposes the existence of a pertinence principle that enables the recognition of differences in the extrinsic conditions of a system, and that such recognition of differences is at the basis of proper intentional phenomena.

https://ift.tt/2EJFtYS

Treatment outcomes of patients with spinal metastases derived from hepatocellular carcinoma

Abstract

Background

The prognosis of hepatocellular carcinoma (HCC) used to be poor, but it has recently improved, which has meant that clinicians have greater opportunity to treat spinal metastases and the associated epidural spinal cord compression. However, there have been few systematic functional studies about HCC-derived spinal metastases. The treatment outcomes of surgical treatment for HCC-derived metastatic spinal tumors were investigated.

Methods

The post-treatment survival period and pain, paralysis, and disturbance of activities of daily living (ADL) were investigated in 60 patients (surgery 25, conservative treatment 35).

Results

The mean post-treatment survival period was 7.4 ± 8.2 months (range 0.3–36 months). Univariate analysis indicated that the following factors influenced survival: the patient's general condition, presence/absence of major internal organ metastasis, serum albumin level, Child–Pugh classification, surgical treatment for spinal metastasis, and bone-modifying agent treatment. In the multivariate analysis of these 6 items, 3 significant factors were extracted: the patient's general condition, the serum albumin level, and bone-modifying agent treatment. Pain significantly improved in both groups (p < 0.001). Paralysis did not change significantly in the surgical group (p = 0.575), but it was significantly aggravated in the conservative treatment group (p = 0.047). The ADL abilities of the surgical group improved significantly (p < 0.001).

Conclusion

Most patients exhibited poor survival. In the conservative treatment group, paralysis was significantly aggravated, and little improvement was seen in the patients' ADL abilities. In the surgical group, the patients' ADL abilities improved significantly, but their paralysis did not. Therefore, surgery should be actively performed for HCC-derived spinal metastasis whenever it is indicated.

https://ift.tt/2JKyGlu

Hemoglobinopathies—genetically diverse, clinically complex, and globally relevant

Summary

Hemoglobinopathies represent the most frequent monogenic disorders worldwide. Migration during recent years led to a profoundly increasing number of patients in countries where the indigenous population has not been affected. This short review will give an overview on etiology, pathogenesis, clinical features, diagnostics, and treatment of the most relevant hemoglobinopathies, i.e., the thalassemias and sickle cell disease.

https://ift.tt/2GWsTLR

Elucidating early CT after pancreatico-duodenectomy: a primer for radiologists

Abstract

Pancreatico-duodenectomy (PD) represents the standard surgical treatment for resectable malignancies of the pancreatic head, distal common bile duct, periampullary region and duodenum, and is also performed to manage selected benign tumours and refractory chronic pancreatitis. Despite improved surgical techniques and acceptable mortality, PD remains a technically demanding, high-risk operation burdened with high morbidity (complication rates 40–50% of patients). Multidetector computed tomography (CT) represents the mainstay modality to rapidly investigate the postoperative abdomen, and to provide a consistent basis for an appropriate choice between conservative, interventional or surgical treatment. However, radiologists require familiarity with the surgically altered anatomy, awareness of expected imaging appearances and possible complications to correctly interpret early post-PD CT studies. This paper provides an overview of surgical indications and techniques, discusses risk factors and clinical manifestations of the usual postsurgical complications, and suggests appropriate techniques and indications for early postoperative CT imaging. Afterwards, the usual, normal early post-PD CT findings are presented, including transient fluid, pneumobilia, delayed gastric emptying, identification of pancreatic gland remnant and of surgical anastomoses. Finally, several imaging examples review the most common and some unusual complications such as pancreatic fistula, bile leaks, abscesses, intraluminal and extraluminal haemorrhage, and acute pancreatitis.

Teaching Points

• Pancreatico-duodenectomy (PD) is a technically demanding surgery burdened with high morbidity (40–50%).

• Multidetector CT is the mainstay technique to investigate suspected complications following PD.

• Interpreting post-PD CT requires knowledge of surgically altered anatomy and expected findings.

• CT showing collection at surgical site supports clinico-biological diagnosis of pancreatic fistula.

• Other complications include biliary leaks, haemorrhage, abscesses and venous thrombosis.

https://ift.tt/2HyN2Vh

Electrically Conductive Scaffold to Modulate and Deliver Stem Cells

This protocol describes fabrication of a cell culture system to allow seeding of stem cells on a conductive polymer scaffold for in vitro electrical stimulation and subsequent in vivo implantation of the stem cell-seeded scaffold using a minimally invasive technique.

https://ift.tt/2H02Wah

Generation and Isolation of Cell Cycle-arrested Cells with Complex Karyotypes

Aneuploidy leads to genome instability, which eventually produces cell cycle-arrested cells with complex karyotypes. This paper provides a simple and convenient method to isolate aneuploid cells with complex karyotypes that cease to divide.

https://ift.tt/2qt7WxH

2-D DOA tracking using variational sparse Bayesian learning embedded with Kalman filter

In this paper, we consider the 2-D direction-of-arrival (DOA) tracking problem. The signals are captured by a uniform spherical array and therefore can be analyzed in the spherical harmonics domain. Exploiting...

https://ift.tt/2vetXFs

Inhibitory effects of eugenol on putative nociceptive response in spinal cord preparation isolated from neonatal rats

Abstract

Eugenol is contained in several plants including clove and is thought to exert an analgesic effect. It has been suggested that the slow ventral root potential induced by ipsilateral dorsal root stimulation in the isolated (typically lumbar) spinal cord of newborn rats reflects the nociceptive response, and this in vitro experimental model is useful to assess the actions of analgesics. To further elucidate neuronal mechanisms of eugenol-induced analgesia, we examined the effects of extracellularly applied eugenol on the nociceptive spinal reflex response. To evaluate the effects of eugenol on putative nociceptive responses, the ipsilateral fifth lumbar (L5) dorsal root was stimulated using a glass suction electrode, and the induced reflex responses were recorded from the L5 and twelfth thoracic (Th12) ventral roots in spinal cord preparations (Th10–L5) from newborn rats (postnatal day 0–3). We found that eugenol (0.25–1.0 mM) caused dose-dependent attenuation of the reflex response and also depressed spontaneous ventral root activity. We also found that the slow ventral root potential was further divided into two components: initial and late components. A lower concentration of eugenol selectively depressed the late component. The inhibitory effects by 1.0 mM eugenol were not reversed by 10 µM capsazepine (TRPV1 antagonist) or 40 µM HC-030031 (TRPA1 antagonist). The depressive effect of eugenol on the reflex response was also confirmed by optical recordings using voltage-sensitive dye. Our report provides additional evidence on the basic neuronal mechanisms of eugenol to support its clinical use as a potential analgesic treatment.

https://ift.tt/2HiDf8e

Absence of a transcription factor halts tooth development in mid-stride

Researchers have found a key role in tooth development for the transcription factor Specificity protein 7, or Sp7. Using an animal model, the researchers found that a lack of Sp7 interrupts the maturation of two types of specialized cells that help create teeth. Such basic knowledge about the development of teeth or bones adds to understanding of craniofacial abnormalities, which are among the most common birth defects in humans.

https://ift.tt/2Hi1tiZ

Acrodose PLus and PL Systems by Haemonetics: Recall - Low pH Readings for Platelets Stored in CLX HP Bag

Audience: Laboratory [Posted 04/13/2018] ISSUE: Haemonetics recently received reports of low pH readings for platelets stored in the CLX HP bag in certain lots of the Acrodose PLus and PL systems. In some instances the drop in pH is accompanied by...

https://ift.tt/2GXwiG9

A Multimodal Imaging Approach Based on Micro-CT and Fluorescence Molecular Tomography for Longitudinal Assessment of Bleomycin-Induced Lung Fibrosis in Mice

We describe a non-invasive multimodal imaging approach based on Micro-CT and fluorescence molecular tomography for longitudinal assessment of the mouse lung fibrosis model induced by double intratracheal instillation of bleomycin.

https://ift.tt/2GY4TUJ

Guidelines for the investigation of chronic diarrhoea in adults: British Society of Gastroenterology, 3rd edition

Chronic diarrhoea is a common problem, hence clear guidance on investigations is required. This is an updated guideline from 2003 for the investigations of chronic diarrhoea commissioned by the Clinical Services and Standards Committee of the British Society of Gastroenterology (BSG). This document has undergone significant revision in content through input by 13 members of the Guideline Development Group (GDG) representing various institutions. The GRADE system was used to appraise the quality of evidence and grading of recommendations.

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Abstract from the Chinese Journal of Hypertension

Prevalence of Elevated Blood Pressure Among Children and Adolescents Aged 6–17 Years Old in Urban Region of Jinan

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Abstract from the Chinese Journal of Hypertension

Application and Evaluation of Screening and Confirmatory Tests for the Diagnosis of Primary Aldosteronism

https://ift.tt/2ISy1NI

Prolonged Baby-Nursing–Related Sphygmomanometric Protection: Breast, Brain, Blood Biomolecules, or Bacteria?

Breastfeeding cannot be praised enough. Since the XIX century,¹ it is known that mother's milk is the right food for the infant, not cow's milk. In the ensuing centuries, the list of advantages has continuously grown, especially as regards prevention of chronic diseases, both for the mother and the child. Among the former, ovarian and breast cancer, obesity, type 2 diabetes, hyperlipidemia, and heart disease deserve to be mentioned. The list for the child is even more relevant. Besides necrotizing enterocolitis, Helicobacter pylori gastritis, general childhood infections, cognitive function, obesity, type 2 diabetes, hypertension, and allergies, also global mortality is benefitted.²

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Primary sarcomatoid urothelial carcinoma of the ureter: a case report and review of the literature

Abstract

Background

Sarcomatoid urothelial carcinoma is a very dangerous malignant tumour derived from the epithelium. Primary sarcomatoid carcinoma of the ureter is extremely rare in clinical practice. The prognosis of this kind of disease is really poor, and there is still not a diagnosis standard in the world.

Case presentation

An 82-year-old female patient who had intermittent waist pain without any other symptoms, had diagnosed as urothelial cancer on computerised tomography urography. Considering the patient's age and quality of life, we made a preserving kidneys resection of the local tumour. The tumour was composed of sarcomatous and carcinomatous elements, and immunohistochemical examination showed that tumour cells were positive for cytokeratin, epithelial membrane antigen, vimentin, and GATA3 markers. There were no complications after 1-hour surgery. After 3 months, there was no signs of recurrence and metastasis.

Conclusion

This case was a patient with sacomatoid urothelial carcinoma. Through a transurethral resection with laser, the patient recovered well, and there was no sign of any recurrence of the tumour after 3 months. With the development of technology and science, more and more cancerous patients' living quality and survival rate were improved. Maybe it is essential for urologists and scientists to entirely understand the characteristics of the sarcomatoid urothelial carcinoma and make a better clinical guideline.

https://ift.tt/2HzETQH

Meningeal carcinomatosis: three case-reports

Abstract

Background

Meningeal carcinomatosis (MC) is characterized by diffuse infiltration of tumor cells in meninges. There is no tumor mass in the brain and parenchyma of the spinal cord. MC is divided into primary and metastatic types. MC cases were previously diagnosed postoperatively or at autopsy. Recent advances in spinal abbreviation cytology and imaging have led to increase in number of reported cases. In this study, we discuss the manifestations of MC patients based on magnetic resonance imaging (MRI) findings, as well as the correlation between the manifestations and pathology.

Case presentation

MC was confirmed in all three cases by lumbar puncture and gadopentetate dimeglumine-enhanced magnetic resonance imaging. Due to different primary diseases, the patients had specific imaging manifestations.

Conclusion

Enhanced MRI examination is extremely sensitive for detecting abnormalities in meninges, which plays a very important role in the diagnosis of MC. Since meninges of some MC patients cannot be enhanced, the enhanced MRI examination cannot be replaced by conventional cerebrospinal abbreviation examination. Attribute to the diversity of MR contrast agents, which could provide higher lesion conspicuity and enhances lesion detection, there may be some more choices to improve the detection rate of MC patients and prolong their survival lifetime.

https://ift.tt/2GUZwFH

Continuous Glucose Monitoring Cost-Effective in T1DM

FRIDAY, April 13, 2018 -- For adults with type 1 diabetes (T1D) with suboptimal control despite using multiple insulin injections, continuous glucose monitoring (CGM) seems cost-effective, with improved glucose control, according to a study...

https://ift.tt/2EJr26Z

Non-Stigmatizing Messages Boost Mental Health Services Support

FRIDAY, April 13, 2018 -- A non-stigmatizing message about serious mental illness (SMI) can increase public support for investing in mental health services, according to a study published online April 1 in the Journal of Health Politics, Policy and...

https://ift.tt/2HxeTFx

Rapid Deployment Valve for Aortic Stenosis Ups Stroke Risk

FRIDAY, April 13, 2018 -- For patients with aortic valve stenosis, treatment with a rapid deployment valve (RDV) is associated with increased rates of new-onset pacemaker implantation and disabling stroke, compared with conventional biological...

https://ift.tt/2ISXkPD

It Costs $2.2 Billion a Year to Treat Antibiotic Resistance

FRIDAY, April 13, 2018 -- Costs associated with treating antibiotic-resistant infections have doubled since 2002, according to a report published in the April issue of Health Affairs. Kenneth E. Thorpe, Ph.D., from the Rollins School of Public...

https://ift.tt/2Hl7xqU

Low-Vision Rehab Improves Several Elements of Visual Function

FRIDAY, April 13, 2018 -- Low-vision (LV) rehabilitation is associated with improvement in several dimensions of visual function, according to a study published online April 12 in JAMA Ophthalmology. Kevin T. Stroupe, Ph.D., from the Edward Hines...

https://ift.tt/2IPLtBU

Politically-Focused Thoughts, Behaviors Tied to Psychopathology

FRIDAY, April 13, 2018 -- Politically-focused intrusive thoughts and associated ritualistic behaviors (PITRBs) are associated with measures of psychopathology and disability, according to a study published online March 31 in the Journal of Anxiety...

https://ift.tt/2HyArSd

Review: Lowest Mortality Risk Seen With ≤100 g Alcohol/Week

FRIDAY, April 13, 2018 -- For current alcohol drinkers, the threshold for the lowest risk of all-cause mortality is about 100 g/week, according to a review published in the April 14 issue of The Lancet. Angela M. Wood, Ph.D., from the University of...

https://ift.tt/2IPL2HM

Adherence to ACS Guidelines Linked to Survival in Colon Cancer

FRIDAY, April 13, 2018 -- Adherence to the American Cancer Society Nutrition and Physical Activity Guidelines for Cancer Survivors (ACS guidelines) is associated with improved survival for patients with stage III colon cancer, according to a study...

https://ift.tt/2HAshII

Soda Tax Cuts Daily Soda, Energy Drink Consumption

FRIDAY, April 13, 2018 -- A soda tax does influence daily consumption of regular soda, energy drinks, and bottled water, according to a study published online April 12 in the American Journal of Preventive Medicine. Yichen Zhong, from Drexel...

https://ift.tt/2IRCfVC

Elder Abuse Not Associated With Risk of Chronic Pain

FRIDAY, April 13, 2018 -- Elder abuse and neglect (EAN) is not tied to the risk of chronic pain, according to a study published online March 30 in the Journal of the American Geriatrics Society. Raudah M. Yunus, M.P.H., from University of Malaya in...

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Colonization sites in carriers of ESBL-producing Gram-negative bacteria

The distribution of Extended-Spectrum Beta-Lactamase-producing Gram-negative bacteria (ESBL-GNB) colonization sites is relevant for infection control guidelines on detection and follow-up of colonization. We q...

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Bone marrow suppression as a complication of total skin helical tomotherapy in the treatment of mycosis fungoides

Abstract

Background

Total skin electron beam therapy (TSEBT) is an effective treatment in mycosis fungoides. Total skin helical tomotherapy (TSHT) may be an alternative to TSEBT and may offer several dosimetric and treatment advantages. There are currently very few published treatment results using TSHT in place of TSEBT for treatment of mycosis fungoides.

Case presentation

Two patients with mycosis fungoides were treated at our institution using TSHT. The first patient was a 69-year-old Caucasian female with stage IVA2 (T2 N3 M0 B2) disease who was treated to a dose of 12 Gy in 8 fractions, with a bone marrow mean dose of 1.66 Gy and V10 = 0.41%. Two weeks after ending treatment the patient developed myelosuppression including grade 4 thrombocytopenia and required blood and platelet transfusions. The second patient was a 29-year-old Caucasian female with stage I (T2 N0 M0 B0) disease. This patient previously had been treated for mycosis fungoides using helical tomotherapy (HT) at a dose of 20 Gy to a localized region and experienced mild thrombocytopenia at that time. The patient then underwent retreatment 17 months later with TSHT to a dose of 12 Gy in 6 fractions with a mean bone marrow dose of 2.3 Gy and V10 = 4.28%. This patient once again experienced myelosuppression that included grade 4 thrombocytopenia. She also required blood and platelet transfusions.

Conclusions

Both patients treated with TSHT experienced severe bone marrow suppression including grade 4 thrombocytopenia. This was more severe than expected considering the relatively low overall prescription dose and despite a planning constraint placed on the bone marrow of a mean dose of < 2 Gy. These outcomes suggest that patients treated using TSHT should be closely monitored for myelosuppression and caution used even when treating to a dose of 12 Gy.

https://ift.tt/2HhV9Ih

Cosmetic outcome as rated by patients, doctors, nurses and BCCT.core software assessed over 5 years in a subset of patients in the TARGIT-A Trial

Abstract

Background

The purpose of this research was to assess agreement between four rating systems of cosmetic outcome measured in a subset of patients with early breast cancer participating in the randomised TARGIT-A trial. TARGIT-A compared risk-adapted single-dose intra-operative radiotherapy (TARGIT-IORT) to whole breast external beam radiotherapy (EBRT).

Methods

Patients, their Radiation Oncologist and Research Nurse completed a subjective cosmetic assessment questionnaire before radiotherapy and annually thereafter for five years. Objective data previously calculated by the validated BCCT.core software which utilizes digital photographs to score symmetry, colour and scar was also used. Agreement was assessed by the Kappa statistic and longitudinal changes were assessed by generalized estimating equations.

Results

Overall, an Excellent-Good (EG) cosmetic result was scored more often than a Fair-Poor (FP) result for both treatment groups across all time points, with patients who received TARGIT-IORT scoring EG more often than those who received EBRT however this was statistically significant at Year 5 only. There was modest agreement between the four rating systems with the highest Kappa score being moderate agreement which was between nurse and doctor scores at Year 1 with Kappa = 0.46 (p < 0.001), 95% CI (0.24, 0.68).

Conclusion

Despite similar overall findings between treatment groups and rating systems, the inter-rater agreement was only modest. This suggests that the four rating systems utilized may not necessarily be used interchangeably and it is arguable that for an outcome such as cosmetic appearance, the patient's point of view is the most important.

Trial Registration

TARGIT-A ISRCTN34086741, Registered 21 July 2004, retrospectively registered.

https://ift.tt/2EJmIEN

Acute acalculous cholecystitis of an intrahepatic gallbladder causing Mirizzis syndrome

We present the case of a young female with symptoms of biliary colic and a biochemical profile consistent with biliary obstruction. Imaging was suspicious for Mirizzi's syndrome. Intraoperatively, the patient was found to have a complete intrahepatic gallbladder causing common hepatic duct compression with final pathology confirming acute cholecystitis. We review the embryological development of the gallbladder as well as clinical presentation of Mirizzi's syndrome. Special consideration for clinical workup and surgical management is discussed.

https://ift.tt/2GV6kXP

Embryonal rhabdomyosarcoma of urinary bladder in an adult patient: an unusual manifestation

An adult man presented with off and on painless haematuria, which was diagnosed as bladder mass on contrast-enhanced CT. He underwent transurethral resection of bladder tumour with complete resection. A diagnosis of embryonal rhabdomyosarcoma was made following histopathology and immunohistochemistry report. The patient was planned for radical cystectomy but was found to have large recurrent infiltrating bladder mass with liver and bone metastasis. Hence, the plan for radical cystectomy was deferred and the patient was counselled regarding chemotherapy (vincristine, cisplatin and doxorubicin regime). The patient tolerated the first cycle of chemotherapy, but his condition deteriorated prior to the second cycle and the patient expired.

https://ift.tt/2qtgOCX

Malignant rhabdoid tumour of the neck in a neonate

Fetal neck masses are rare, and present a challenge antenatally, during delivery and in making a diagnosis. In this report, we detail the presentation of a neonate with a neck mass diagnosed in the third trimester. The baby was delivered by ex utero intrapartum therapy (EXIT). Investigations sent included an MRI with limited CT cuts, and a biopsy, which lead to the diagnosis of a malignant rhabdoid tumour. This is rare and the overall survival is low.

https://ift.tt/2GWEY3w

Infertility: an out-of-the-box cause of postmenopausal endometrial thickening

Description

The presence of intrauterine foreign bodies (IFBs) is a rare condition that may lead to chronic endometritis through local inflammation. According to literature, IFB may be the cause of 0.02% to 0.15% of the cases of infertility, and of abnormal uterine bleeding, pelvic pain and abnormal vaginal discharge.1

We present the case of a 63-year-old, nulligravida, postmenopausal woman who complained of scarce genital bleeding and vaginal discharge for about 1 year. The patient denied other symptoms like fever, pelvic pain, dyspareunia or weight loss. In terms of relevant previous history, this patient had a laparotomy and myomectomy performed 30 years before because of a transmural uterine leiomyoma diagnosed in the workup for primary infertility. Even after surgery, no pregnancy was achieved. Menopause occurred at 52 years of age and no hormonal replacement therapy was used. No other relevant previous medical or surgical history was found.

On...

https://ift.tt/2qqExUa

Anti-TNF therapy-induced lupus erythematosus-like syndrome in a patient treated with adalimumab for cutaneous psoriasis

A 44-year-old woman with cutaneous psoriasis and no history of joint involvement recently treated with adalimumab was admitted to the inpatient Internal Medicine service for uncontrolled, severe joint pain so debilitating that it limited her activities of daily living and prevented her from working as a medical technologist. She had stopped taking adalimumab 3 weeks prior to presentation after receiving approximately 2.5 months of therapy for cutaneous psoriasis unresponsive to trials of topical steroids and methotrexate. Antinuclear antibody and anti-double-stranded DNA antibodies were positive at high titres. She received a course of oral corticosteroids with improvement in her symptoms.

https://ift.tt/2GUyLW1

Ruptured choledochal cyst during early pregnancy with successful fetomaternal outcome

Choledochal cyst is a rare congenital malformation which is usually found in young children and adolescents but can rarely present in the adult age group. It can present with several complications like cholangitis, pancreatitis, biliary cirrhosis, portal hypertension, liver abscess, malignancy and rarely spontaneous rupture (in 2% of cases) causing biliary peritonitis. A case of spontaneous rupture of choledochal cyst during second trimester of pregnancy is reported where the patient was managed by minimal surgery, peritoneal washout, placement of T-tube and planned for definitive treatment in the postpartum period. The pregnancy continued till 35 weeks with favourable fetomaternal outcome.

https://ift.tt/2quPP9S

Orbital cystic schwannoma masquerading as hydatid cyst

Gradually increasing abaxial proptosis in a middle-aged female patient revealed a large well-defined cystic lesion behind the globe extending till the orbital apex. B scan ultrasound and CT findings were favouring a diagnosis of orbital hydatid cyst. Thus as a diagnostic/curative surgical protocol, the cystic lesion was removed in total. However, intraoperative gross specimen examination was not classical of hydatid cyst, thus a further histopathological evaluation was carried out, which confirmed the diagnosis of orbital schwannoma with extensive cystic degeneration. Postoperatively the clinical course was uneventful at the end of 1 year.

https://ift.tt/2GW2myf

Meningitis due to scrub typhus: the importance of a differential diagnosis in an endemic area

A patient with fever and neck stiffness was treated as partially treated bacterial meningitis based on history, examination and cerebrospinal fluid analysis. After initial improvement with ceftriaxone, vancomycin and dexamethasone, symptoms recurred. Fever resolved promptly after treatment was started with doxycycline, when scrub typhus immunoglobulin M test came positive. Meningitis is a well-known complication of scrub typhus. However, scrub typhus is seldom considered in the differential diagnosis of meningitis in the Indian subcontinent. Early diagnosis and prompt institution of doxycycline therapy may lead to early cure of scrub typhus even when features of meningitis supervene. However, ceftriaxone which is commonly used to treat bacterial meningitis is suboptimal in the treatmenwgt36t of scrub typhus.

https://ift.tt/2qvbmPF

Misguided urinary catheter: an uncommon complication of a common solution

Description 

A 61-year-old man was wheeled in to our emergency triage bleeding profusely from his mouth and nose in an unconscious state. His Glasgow Coma Scale was 7 and was intubated for airway safety. A failed anterior nasal packing was followed by insertion of a Foley urinary catheter through the right nostril to secure posterior nasal packing and haemostasis. CT of the brain following nasal packing showed diffuse traumatic subarachnoid haemorrhage and basifrontal contusions with multiple fractures of the anterior cranial fossa, cribriform plate including the frontal sinus. Multiple specs of air in the frontal lobe was initially mistaken as pneumocephalus (Hounsfield unit –971) (figure 1). The Foley catheter had inadvertently found its way to the brain through the cribriform plate, and the bulb was inflated just above the defect (figure 2). The catheter was deflated and removed soon after imaging. The patient underwent a...

https://ift.tt/2GVOFzn

Liver Failure in Advanced Adult-onset Polycystic Kidney Disease

Polycystic liver disease is the most common extrarenal manifestation of autosomal dominant polycystic kidney disease (ADPKD). Hepatic cysts are typically incidental findings, with occasional complications including cyst haemorrhage, infection and rupture. In contrast to the typically benign course of polycystic liver disease, we present a rare case of fatal decompensated liver failure in a patient with ADPKD. This is a case of a 58-year-old man with end-stage renal disease on haemodialysis presenting with new-onset ascites and decompensated liver failure following bilateral nephrectomy. Cirrhosis in ADPKD is a late manifestation of the disease, but it should be considered in the perioperative risk of patients with ADPKD.

https://ift.tt/2qsOnVC

Molecular Biomarker to Assist in Diagnosing Abdominal Sepsis upon ICU Admission

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 8, Page 1070-1073, April 15, 2018.


https://ift.tt/2JKsvO6

Asthma: From Diagnosis to Endotype to Treatment

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 8, Page 1065-1067, April 15, 2018.


https://ift.tt/2v9YCnc

Unproven and Expensive before Proven and Cheap: Extracorporeal Membrane Oxygenation versus Prone Position in Acute Respiratory Distress Syndrome

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 8, Page 991-993, April 15, 2018.


https://ift.tt/2JFw9sC

Evaluating UK National Guidance for Screening of Children for Tuberculosis. A Prospective Multicenter Study

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 8, Page 1058-1064, April 15, 2018.


https://ift.tt/2EJqezd

Food and Drug Administration–mandated Trials of Long-Acting β-Agonist Safety in Asthma. Bang for the Buck?

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 8, Page 987-990, April 15, 2018.


https://ift.tt/2JKrPso

The Plausibility of “Bronchiolotrauma”

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 8, Page 1086-1087, April 15, 2018.


https://ift.tt/2vjbSpZ

The WHO 2018 Hand Hygiene Campaign: Make a Difference—Prevent Sepsis in Health Care

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 8, Page 985-986, April 15, 2018.


https://ift.tt/2JIF5O7

Reply to Borges: The Plausibility of “Bronchiolotrauma”

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 8, Page 1087-1088, April 15, 2018.


https://ift.tt/2veb9pQ

Transpulmonary Pressure–based Mechanical Ventilation in Acute Respiratory Distress Syndrome. From Theory to Practice?

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 8, Page 977-978, April 15, 2018.


https://ift.tt/2JJYQos

Erratum: The Plasma Concentration of MUC5B Is Associated with Clinical Outcomes in Paraquat-poisoned Patients

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 8, Page 1093-1093, April 15, 2018.


https://ift.tt/2vjbBmX

Depletion of Airway Submucosal Glands and TP63+KRT5+ Basal Cells in Obliterative Bronchiolitis

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 8, Page 1045-1057, April 15, 2018.


https://ift.tt/2JInQME

Esophageal Manometry and Regional Transpulmonary Pressure in Lung Injury

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 8, Page 1018-1026, April 15, 2018.


https://ift.tt/2EIOkda

Epithelial Progenitor Cells Take Center Stage in Lung Transplantation

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 8, Page 981-983, April 15, 2018.


https://ift.tt/2JJuTEP

Reply to Rodrigues et al.: Increasing Physical Activity in Daily Life in Chronic Obstructive Pulmonary Disease: To Solve the Puzzle, Every Piece Counts

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 8, Page 1089-1090, April 15, 2018.


https://ift.tt/2vaVHLj

Activated Leukocyte Cell Adhesion Molecule Stimulates the T-Cell Response in Allergic Asthma

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 8, Page 994-1008, April 15, 2018.


https://ift.tt/2JHOLbz

Increasing Physical Activity in Daily Life in Chronic Obstructive Pulmonary Disease: To Solve the Puzzle, Every Piece Counts

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 8, Page 1088-1089, April 15, 2018.


https://ift.tt/2EIlv0E

Ventilator Circuit Trash May Be a Research Treasure

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 8, Page 979-980, April 15, 2018.


https://ift.tt/2JI097n

Novel Method for Noninvasive Sampling of the Distal Airspace in Acute Respiratory Distress Syndrome

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 8, Page 1027-1035, April 15, 2018.


https://ift.tt/2EHMFoz

Erratum: Randomized Controlled Trial of Urokinase versus Placebo for Nondraining Malignant Pleural Effusion

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 8, Page 1092-1093, April 15, 2018.


https://ift.tt/2JGL7i8

DELPHIning Diagnostic Criteria for Chronic Hypersensitivity Pneumonitis

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 8, Page 980-981, April 15, 2018.


https://ift.tt/2EITNkg

Molecular and Metabolic Basis of Clear Cell Carcinoma of the Kidney

Renal cell carcinoma (RCC) is a heterogenous group of tumors, >70% of which belong to the category of clear cell carcinoma. In recent years, crucial advances have been made in our understanding of the molecular and metabolic basis of clear cell carcinoma. This tumor manifests significant alterations in the cellular metabolism, so that the tumor cells preferentially induce the hypoxia response pathway using aerobic glycolysis, rather than the normal oxidative phosphorylation for energy. Most of the clear cell carcinomas (sporadic as well as familial) have mutations and deletions in the VHL gene located at 3p (p3.25). Normally, pVHL plays a crucial role in the proteasomal degradation of hypoxia-inducible factors (HIF)1 and HIF2. Lack of a functioning pVHL owing to genetic alterations results in stabilization and accumulation of these factors, which promotes cell growth, cell proliferation, and angiogenesis, contributing to a neoplastic phenotype. Several other genes normally located adjacent to VHL (BAP1, SETD2, PBRM1) may also be lost. These are tumor suppressor genes whose loss not only plays a role in carcinogenesis but may also influence the clinical course of these neoplasms. In addition, interaction among a variety of other genes located at several different chromosomes may also play a role in the genesis and progression of clear cell carcinoma.

https://ift.tt/2qsaYCu

Aggressive Variants of Papillary Thyroid Carcinoma: Hobnail, Tall Cell, Columnar, and Solid

Papillary thyroid carcinomas are the most common endocrine cancer and are usually associated with good survival. However, some variants of papillary thyroid carcinomas may behave more aggressively than classic papillary thyroid carcinomas. The tall cell variant of papillary thyroid carcinoma is the most common aggressive variant of papillary thyroid carcinoma. The aggressive behavior has been ascribed to the histologic subtype and/or to the clinicopathologic features, an issue that remains controversial. The columnar variant of papillary thyroid carcinoma can be aggressive, particularly in older patients, with larger tumors showing a diffusely infiltrative growth pattern and extrathyroidal extension. A papillary thyroid carcinoma is designated as solid/trabecular variant when all or nearly all of a tumor not belonging to any of the other variants has a solid, trabecular, or nested (insular) appearance. This tumor must be distinguished from poorly differentiated thyroid carcinoma which has the same growth pattern but lacks nuclear features of papillary thyroid carcinoma and may show tumor necrosis and high mitotic activity. New to the fourth edition of the WHO Classification of Tumours of Endocrine Organs, the hobnail variant of papillary thyroid carcinoma is a moderately differentiated papillary thyroid carcinoma variant with aggressive clinical behavior and significant mortality. All of these variants are histologically unique and important to recognize due to their aggressive behavior.

https://ift.tt/2IRhU2U

Incorporating Advances in Molecular Pathology Into Brain Tumor Diagnostics

Recent advances in molecular pathology have reshaped the practice of brain tumor diagnostics. The classification of gliomas has been restructured with the discovery of isocitrate dehydrogenase (IDH) 1/2 mutations in the vast majority of lower grade infiltrating gliomas and secondary glioblastomas (GBM), with IDH-mutant astrocytomas further characterized by TP53 and ATRX mutations. Whole-arm 1p/19q codeletion in conjunction with IDH mutations now define oligodendrogliomas, which are also enriched for CIC, FUBP1, PI3K, NOTCH1, and TERT-p mutations. IDH-wild-type (wt) infiltrating astrocytomas are mostly primary GBMs and are characterized by EGFR, PTEN, TP53, NF1, RB1, PDGFRA, and CDKN2A/B alterations, TERT-p mutations, and characteristic copy number alterations including gains of chromosome 7 and losses of 10. Other clinically and genetically distinct infiltrating astrocytomas include the aggressive H3K27M-mutant midline gliomas, and smaller subsets that occur in the setting of NF1 or have BRAF V600E mutations. Low-grade pediatric gliomas are both genetically and biologically distinct from their adult counterparts and often harbor a single driver event often involving BRAF, FGFR1, or MYB/MYBL1 genes. Large scale genomic and epigenomic analyses have identified distinct subgroups of ependymomas tightly linked to tumor location and clinical behavior. The diagnosis of embryonal neoplasms also integrates molecular testing: (I) 4 molecularly defined, biologically distinct subtypes of medulloblastomas are now recognized; (II) 3 histologic entities have now been reclassified under a diagnosis of "embryonal tumor with multilayered rosettes (ETMR), C19MC-altered"; and (III) atypical teratoid/rhabdoid tumors (AT/RT) now require SMARCB1 (INI1) or SMARCA4 (BRG1) alterations for their diagnosis. We discuss the practical use of contemporary biomarkers for an integrative diagnosis of central nervous system neoplasia.

https://ift.tt/2HjTZfq

HPV-related Oropharyngeal Carcinoma: A Review of Clinical and Pathologic Features With Emphasis on Updates in Clinical and Pathologic Staging

There has been a sharp increase in the incidence of the human papilloma virus–related oropharyngeal squamous cell carcinoma, partly due to the increasingly widespread awareness and recognition of this entity. This review assimilates the recent histopathologic classifications, staging systems, rapidly expanding research base and developments in management of human papilloma virus–related oropharyngeal squamous cell carcinoma and summarizes their implications for routine diagnostic practice. Differential diagnoses and their cytologic appearances are detailed and the utility of p16 staining and other immunohistochemistry testing is discussed.

https://ift.tt/2EJ0ItP

Extraneuraxial Hemangioblastoma: Clinicopathologic Features and Review of the Literature

Extraneuraxial hemangioblastoma occurs in nervous paraneuraxial structures, somatic tissues, and visceral organs, as part of von Hippel-Lindau disease (VHLD) or in sporadic cases. The VHL gene plausibly plays a key role in the initiation and tumorigenesis of both central nervous system and extraneuraxial hemangioblastoma, therefore, the underlying molecular and genetic mechanisms of the tumor growth are initially reviewed. The clinical criteria for the diagnosis of VHLD are summarized, with emphasis on the distinction of sporadic hemangioblastoma from the form fruste of VHLD (eg, hemangioblastoma-only VHLD). The world literature on the topic of extraneuraxial hemangioblastomas has been comprehensively reviewed with ∼200 cases reported to date: up to 140 paraneuraxial, mostly of proximal spinal nerve roots, and 65 peripheral, 15 of soft tissue, 6 peripheral nerve, 5 bone, and 39 of internal viscera, including 26 renal and 13 nonrenal. A handful of possible yet uncertain cases from older literature are not included in this review. The clinicopathologic features of extraneuraxial hemangioblastoma are selectively presented by anatomic site of origin, and the differential diagnosis is emphasized in these subsets. Reference is made also to 10 of the authors' personal cases of extraneuraxial hemangioblastomas, which include 4 paraneuraxial and 6 peripheral (2 soft tissue hemangioblastoma and 4 renal).

https://ift.tt/2HjTLVC

Scaling the Peaks Research Protocol: understanding the barriers and drivers to providing and using dementia-friendly community services in rural areas--a mixed methods study

Introduction

Scaling the Peaks is a cross-disciplinary research study that draws on medical ethnography, human geography and Geospatial Information Science (GIS) to address the issues surrounding the design and delivery of dementia-friendly services in rural communities. The research question seeks to understand the barriers and drivers to the development of relevant, robust, reliable and accessible services that make a difference among older rural families affected by dementia.

Methods and analysis

This mixed methods study recruits both families affected by dementia who reside within the Peak District National Park, Derbyshire, and their service providers. The study explores the expectations and experiences of rural dementia by adopting a three-part approach¹: longitudinal ethnographic enquiry with up to 32 families affected by dementia (aged 70 years plus) who identify themselves as rural residents²; ethnographic semistructured interviews and systematic observations of a range of statutory, third sector, private and local community initiatives that seek to support older people living with dementia³; and geospatial visual mapping of the qualitative and quantitative data. The ethnographic data will be used to explore the ideas of belonging in a community, perceptions of place and identity to determine the factors that influence everyday decisions about living well with dementia and, for the providers, working in a rural community. The geospatial component of the study seeks to incorporate quantitative and qualitative data, such as types, locations and allocation of services to produce an interactive web-based map for local communities to determine the future design and delivery of services when considering dementia-friendly services.

Ethics and dissemination

The study is approved by the Leeds and Humberside Health Research Authority 16/YH/0163. The study is also approved by other participating organisations as required by their own governance procedures. The study includes people with dementia and as such adheres to the ethical considerations when including people with dementia. A publicly available interactive visual map of the findings will be produced in relation to current services related to location and, by default, identify gaps in provision. Formal reports and dissemination activities will be undertaken in collaboration with the study advisory group members.

Study progress

The recruitment began in September 2016. The data analysis commenced June 2017, using 59 provider interviews and 27 family participants. Data collection will be completed June 2018.

Note on terminology

Please note that the term 'families affected by dementia' is the preferred term of usage by the family members of the Scaling the Peaks Study Advisory Group. The group wish to emphasise that they consider this term to be more representative of their lives than the term living with dementia.

Trial registration number

NIHR IRAS 188103; Pre-results.

https://ift.tt/2JKosBo

The role of psychological factors in the perpetuation of pain intensity and disability in people with chronic shoulder pain: a systematic review

Introduction

Chronic shoulder pain is a very complex syndrome, and the mechanisms involved in its perpetuation remain unclear. Psychological factors appear to play a role in the perpetuation of symptoms in people with shoulder chronicity. The purpose of this systematic review is to examine the role of psychological factors in the perpetuation of symptoms (pain intensity and disability) in people with chronic shoulder pain.

Methods and analysis

A systematic search was performed on PubMed, AMED, CINAHL, PubPsych and EMBASE from inception to July 2017. Longitudinal studies with quantitative designs analysing the role of psychological factors on pain intensity, disability or both were included. The methodological quality of the included studies was evaluated with an adapted version of the Newcastle Ottawa Scale. The level of evidence per outcome was examined using the Grading of Recommendations Assessment, Development and Evaluation approach.

Results

A total of 27 articles were included with a sample of 11 176 people with chronic shoulder pain. The risk of bias ranges from 7/21 to 13/21 across the studies. The quality of the evidence was very low. High levels of self-efficacy, resilience and expectations of recovery were significantly associated with low levels of pain intensity and disability. Inversely, high levels of emotional distress, depressive symptoms, anxiety, preoperative concerns, fear-avoidance beliefs, somatisation and pain catastrophising were significantly associated with high levels of pain intensity and disability.

Discussion

Our results suggest that psychological factors may influence the perpetuation of pain intensity and disability, with very low evidence. A meta-analysis was not carried out due to the heterogeneity of the included studies so results should be interpreted with caution.

PROSPERO trial registration number

CRD42016036366.

https://ift.tt/2JE13Sp