bluuebunny/crossref_metadata_2025 huggingface dataset:
Critical Illness Is Associated With Impaired Gallbladder Emptying as Assessed by 3D Ultrasound
Authors: Plummer Mark P. , Kar Palash , Cousins Caroline E. , Hausken Trygve , Lange Kylie , Chapman Marianne J. , Jones Karen L. , Horowitz Michael , Deane Adam M.
Published: April 2016

Objective:

To quantify gallbladder dysfunction during critical illness.

Design:

Prospective observational comparison study of nutrient-stimulated gallbladder emptying in health and critical illness.

Setting:

Single-centre mixed medical/surgical ICU.

Patients:

Twenty-four mechanically ventilated critically ill patients suitable to receive enteral nutrition were compared with 12 healthy subjects.

Interventions:

Participants were studied after an 8-hour fast. Between 0 and 120 minutes, high-fat nutrient (20% intralipid) was infused via a postpyloric catheter into the duodenum at 2 kcal/min.

Measurements and Main Results:

Three-dimensional images of the gallbladder were acquired at 30-minute intervals from –30 to 180 minutes. Ejection fraction (%) was calculated as changes between 0 and 120 minutes. Blood samples were obtained at 30-minute intervals for plasma cholecystokinin. Data are mean (sd) or median [interquartile range]. In the critically ill, fasting gallbladder volumes (critically ill, 61 mL [36–100 mL] vs healthy, 22 mL [15–25] mL; p < 0.001] and wall thickness (0.45 mm [0.15 mm] vs 0.26 mm [0.08 mm]; p < 0.001] were substantially greater, and sludge was evident in the majority of patients (71% vs 0%). Nutrient-stimulated emptying was incomplete in the critically ill after 120 minutes but was essentially complete in the healthy individuals (22 mL [9–66 mL] vs 4 mL [3–5 mL]; p < 0.01]. In five critically ill patients (21%), there was no change in gallbladder volume in response to nutrient, and overall ejection fraction was reduced in the critically ill (50% [8–83%] vs 77 [72–84%]; p = 0.01]. There were no differences in fasting or incremental cholecystokinin concentrations.

Conclusions:

Fasted critically ill patients have larger, thicker-walled gallbladders than healthy subjects and nutrient-stimulated gallbladder emptying is impaired with “gallbladder paresis” occurring in approximately 20%.
A Time-Motion Study of ICU Workflow and the Impact of Strain*
Authors: Hefter Yosefa , Madahar Purnema , Eisen Lewis A. , Gong Michelle N.
Published: April 2016

Objective:

Understanding ICU workflow and how it is impacted by ICU strain is necessary for implementing effective improvements. This study aimed to quantify how ICU physicians spend time and to examine the impact of ICU strain on workflow.

Design:

Prospective, observational time-motion study.

Setting:

Five ICUs in two hospitals at an academic medical center.

Subjects:

Thirty attending and resident physicians.

Interventions:

None.

Measurements and Main Results:

In 137 hours of field observations, the most time—84 hours (62% of total observation time)—was spent on professional communication. Reviewing patient data and documentation occupied a combined 52 hours (38%), whereas direct patient care and education occupied 24 hours (17%) and 13 hours (9%), respectively. The most frequently used tool was the computer, used in tasks that occupied 51 hours (37%). Severity of illness of the ICU on day of observation was the only strain factor that significantly impacted work patterns. In a linear regression model, increase in average ICU Sequential Organ Failure Assessment was associated with more time spent on direct patient care (β = 4.3; 95% CI, 0.9–7.7) and education (β = 3.2; 95% CI, 0.7–5.8), and less time spent on documentation (β = –7.4; 95% CI, –11.6 to –3.2) and on tasks using the computer (β = –7.8; 95% CI, –14.1 to –1.6). These results were more pronounced with a combined strain score that took into account unit census and Sequential Organ Failure Assessment score. After accounting for ICU type (medical vs surgical) and staffing structure (resident staffed vs physician assistant staffed), results changed minimally.

Conclusion:

Clinicians spend the bulk of their time in the ICU on professional communication and tasks involving computers. With the strain of high severity of illness and a full unit, clinicians reallocate time from documentation to patient care and education. Further efforts are needed to examine system-related aspects of care to understand the impact of workflow and strain on patient care.
Elevated Leukocyte Azurophilic Enzymes in Human Diabetic Ketoacidosis Plasma Degrade Cerebrovascular Endothelial Junctional Proteins*
Authors: Woo Martin M. H. , Patterson Eric K. , Clarson Cheril , Cepinskas Gediminas , Bani-Yaghoub Mahmud , Stanimirovic Danica B. , Fraser Douglas D.
Published: April 2016

Objective:

Diabetic ketoacidosis in children is associated with vasogenic cerebral edema, possibly due to the release of destructive polymorphonuclear neutrophil azurophilic enzymes. Our objectives were to measure plasma azurophilic enzyme levels in children with diabetic ketoacidosis, to correlate plasma azurophilic enzyme levels with diabetic ketoacidosis severity, and to determine whether azurophilic enzymes disrupt the blood-brain barrier in vitro.

Design:

Prospective clinical and laboratory study.

Setting:

The Children’s Hospital, London Health Sciences Centre.

Subjects:

Pediatric type 1 diabetes patients; acute diabetic ketoacidosis or age-/sex-matched insulin-controlled.

Measurements and Main Results:

Acute diabetic ketoacidosis in children was associated with elevated polymorphonuclear neutrophils. Plasma azurophilic enzymes were elevated in diabetic ketoacidosis patients, including human leukocyte elastase (p < 0.001), proteinase-3 (p < 0.01), and myeloperoxidase (p < 0.001). A leukocyte origin of human leukocyte elastase and proteinase-3 in diabetic ketoacidosis was confirmed with buffy coat quantitative real-time polymerase chain reaction (p < 0.01). Of the three azurophilic enzymes elevated, only proteinase-3 levels correlated with diabetic ketoacidosis severity (p = 0.002). Recombinant proteinase-3 applied to human brain microvascular endothelial cells degraded both the tight junction protein occludin (p < 0.05) and the adherens junction protein VE-cadherin (p < 0.05). Permeability of human brain microvascular endothelial cell monolayers was increased by recombinant proteinase-3 application (p = 0.010).

Conclusions:

Our results indicate that diabetic ketoacidosis is associated with systemic polymorphonuclear neutrophil activation and degranulation. Of all the polymorphonuclear neutrophil azurophilic enzymes examined, only proteinase-3 correlated with diabetic ketoacidosis severity and potently degraded the blood-brain barrier in vitro. Proteinase-3 might mediate vasogenic edema during diabetic ketoacidosis, and selective proteinase-3 antagonists may offer future vascular- and neuroprotection.
Comparative Effects of Volutrauma and Atelectrauma on Lung Inflammation in Experimental Acute Respiratory Distress Syndrome
Authors: Güldner Andreas , Braune Anja , Ball Lorenzo , Silva Pedro L. , Samary Cynthia , Insorsi Angelo , Huhle Robert , Rentzsch Ines , Becker Claudia , Oehme Liane , Andreeff Michael , Vidal Melo Marcos F. , Winkler Tilo , Pelosi Paolo , Rocco Patricia R. M. , Kotzerke Jörg , Gama de Abreu Marcelo
Published: April 2016

Objective:

Volutrauma and atelectrauma promote ventilator-induced lung injury, but their relative contribution to inflammation in ventilator-induced lung injury is not well established. The aim of this study was to determine the impact of volutrauma and atelectrauma on the distribution of lung inflammation in experimental acute respiratory distress syndrome.

Design:

Laboratory investigation.

Setting:

University-hospital research facility.

Subjects:

Ten pigs (five per group; 34.7–49.9 kg)

Interventions:

Animals were anesthetized and intubated, and saline lung lavage was performed. Lungs were separated with a double-lumen tube. Following lung recruitment and decremental positive end-expiratory pressure trial, animals were randomly assigned to 4 hours of ventilation of the left (ventilator-induced lung injury) lung with tidal volume of approximately 3 mL/kg and 1) high positive end-expiratory pressure set above the level where dynamic compliance increased more than 5% during positive end-expiratory pressure trial (volutrauma); or 2) low positive end-expiratory pressure to achieve driving pressure comparable with volutrauma (atelectrauma). The right (control) lung was kept on continuous positive airway pressure of 20 cm H2O, and Co
2 was partially removed extracorporeally.

Measurements and Main Results:

Regional lung aeration, specific [18F]fluorodeoxyglucose uptake rate, and perfusion were assessed using computed and positron emission tomography. Volutrauma yielded higher [18F]fluorodeoxyglucose uptake rate in the ventilated lung compared with atelectrauma (median [interquartile range], 0.017 [0.014–0.025] vs 0.013 min–1 [0.010–0.014 min–1]; p < 0.01), mainly in central lung regions. Volutrauma yielded higher [18F]fluorodeoxyglucose uptake rate in ventilator-induced lung injury versus control lung (0.017 [0.014–0.025] vs 0.011 min–1 [0.010–0.016 min–1]; p < 0.05), whereas atelectrauma did not. Volutrauma decreased blood fraction at similar perfusion and increased normally as well as hyperaerated lung compartments and tidal hyperaeration. Atelectrauma yielded higher poorly and nonaerated lung compartments, and tidal recruitment. Driving pressure increased in atelectrauma.

Conclusions:

In this model of acute respiratory distress syndrome, volutrauma promoted higher lung inflammation than atelectrauma at comparable low tidal volume and lower driving pressure, suggesting that static stress and strain are major determinants of ventilator-induced lung injury.
Histopathology of Septic Acute Kidney Injury: A Systematic Review of Experimental Data
Authors: Kosaka Junko , Lankadeva Yugeesh R. , May Clive N. , Bellomo Rinaldo
Published: April 2016

Objective:

The histopathologic changes associated with septic acute kidney injury are poorly understood, in part, because of the lack of biopsy data in humans. Animal models of septic acute kidney injury may help define such changes. Therefore, we performed a systematic review of the histopathologic changes found in modern experimental septic acute kidney injury models.

Data Sources:

MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, and PubMed (from January 2007 to February 2015).

Study Selection:

We reviewed experimental studies reporting findings on the histopathology of contemporary experimental septic acute kidney injury.

Data Extraction:

We focused on the presence or the absence of acute tubular necrosis, tubular cell apoptosis, and other nonspecific findings.

Data Synthesis:

We identified 102 studies in 1,059 animals. Among the 1,059 animals, 53 (5.0%) did not have any renal histopathologic changes, but acute tubular necrosis was found in 184 (17.4%). The prevalence of acute tubular necrosis was not related to animal size or model of sepsis and was only found in models with low cardiac output and decreased renal blood flow (p < 0.0001). Only 21 studies (170 animals) assessed the prevalence of tubular cell apoptosis, which was reported in 158 animals (92.9%). The prevalence of tubular cell apoptosis was significantly higher in studies using small animals (p < 0.0001) and in peritonitis models (p < 0.0001). Simultaneous acute tubular necrosis and tubular cell apoptosis was rare (55 animals [32.4%]) and only seen with decreased cardiac output and renal blood flow. Nonspecific changes (vacuolization of tubular cells, loss of brush border, and tubular cell swelling) were each observed in 423 (39.9%), 250 (23.6%) and 243 (22.9%) animals, respectively.

Conclusions:

In models of experimental septic acute kidney injury in contemporary articles, acute tubular necrosis was relatively uncommon and, when present, reflected the presence of an associated low cardiac output or low renal blood flow syndrome. Tubular cell apoptosis seemed frequent in the few studies in which it was investigated. Nonspecific morphologic changes, however, were the most common histopathologic findings.
Liberal Versus Conventional Glucose Targets in Critically Ill Diabetic Patients: An Exploratory Safety Cohort Assessment
Authors: Di Muzio Francesca , Presello Barbara , Glassford Neil J. , Tsuji Isabela Y. , Eastwood Glenn M. , Deane Adam M. , Ekinci Elif I. , Bellomo Rinaldo , Mårtensson Johan
Published: April 2016

Objectives:

To assess the feasibility, safety, and impact on relative hypoglycemia of liberal versus conventional blood glucose concentration targets in critically ill diabetic patients.

Design:

Prospective, open-label, sequential-period exploratory study.

Setting:

A 22-bed multidisciplinary ICU of a tertiary care hospital in Australia.

Patients:

Eighty adult diabetic patients, 40 from the conventional before period and 40 from the liberal after period.

Interventions:

Blood glucose concentration targets were 6–10 mmol/L during the before period and 10–14 mmol/L during the after period.

Measurements and Main Results:

We used admission glycated hemoglobin to estimate premorbid baseline blood glucose concentration. We defined glycemic distance as the difference between blood glucose concentration in ICU and baseline blood glucose concentration. During the first 48 ICU hours, we recorded absolute (blood glucose concentration, < 3.9 mmol/L) and relative (glycemic distance, > 30% below baseline) hypoglycemia rates, insulin administration, and outcomes. The groups had similar baseline characteristics. We observed a negative glycemic distance in 248 of 488 blood glucose concentrations (50.8%) during the before period and 164 of 485 (33.8%) during the after period (p < 0.001). We detected relative hypoglycemia in 20 (50.0%) and nine (22.5%) patients in the before and after periods, respectively (p = 0.01). On day 1, 50.0% and 16.7% received insulin in the before and after periods (p = 0.007). ICU and hospital length of stay and mortality were similar between groups.

Conclusions:

In a safety cohort of critically ill diabetic patients, a blood glucose concentration target of 10–14 mmol/L resulted in fewer episodes of negative glycemic distance or relative hypoglycemia and reduced insulin administration compared with a target of 6–10 mmol/L.
Measuring Adaptive Coping of Hospitalized Patients With a Severe Medical Condition: The Sickness Insight in Coping Questionnaire*
Authors: Boezeman Edwin J. , Hofhuis José G. M. , Hovingh Aly , Cox Christopher E. , de Vries Reinout E. , Spronk Peter E.
Published: April 2016

Objectives:

Adaptive coping strategies are associated with less psychological distress. However, there is no brief, specific, and validated instrument for assessing adaptive coping among seriously ill patients. Our objective was to examine the validity and patient-proxy agreement of a novel instrument, the Sickness Insight in Coping Questionnaire.

Design:

A cross-sectional design which included two related studies.

Setting:

A single university-affiliated Dutch hospital.

Subjects:

Hospitalized patients (study 1) and ICU-patients and proxies (study 2).

Interventions:

None.

Measurements and Main Results:

Study 1 (n = 103 hospitalized patients) addressed the Sickness Insight in Coping Questionnaire’s performance relative to questionnaires addressing similar content areas. Coping subscales of the BRIEF COPE, Illness Cognition Questionnaire, and Utrecht Coping List were used as comparator measures in testing the construct validity of the Sickness Insight in Coping Questionnaire-subscales (fighting spirit, toughness, redefinition, positivism, and non-acceptance). The Sickness Insight in Coping Questionnaire had good internal consistency (0.64 ≤ α ≤ 0.79), a clear initial factor structure, and fair convergent (0.24 ≤ r ≤ 0.50) and divergent (r, ≤ 0.12) construct validity. Study 2 examined the performance of the Sickness Insight in Coping Questionnaire among 100 ICU patients and their close family members. This study showed that the Sickness Insight in Coping Questionnaire has good structural validity (confirmatory factor analyses with Comparative Fit Index > 0.90 and Root Mean Square Error of Approximation < 0.08) and moderate (r, 0.37; non-acceptance) to strong (r, > 0.50; fighting spirit, toughness, redefinition, and positivism) patient-close proxy agreement.

Conclusions:

Overall, the Sickness Insight in Coping Questionnaire has good psychometric properties. ICU clinicians can use the Sickness Insight in Coping Questionnaire to gain insight in adaptive coping style of patients through ratings of patients or their close family members.
Incidence and Etiology of Potentially Preventable ICU Readmissions*
Authors: Al-Jaghbeer Mohammed J. , Tekwani Seema S. , Gunn Scott R. , Kahn Jeremy M.
Published: April 2016

Objectives:

The rate of unplanned ICU readmissions is often considered a measure of hospital performance. However, the degree to which these readmissions are preventable and the causes of preventable readmissions are unknown, creating uncertainty about the feasibility and value of reducing ICU readmission rates. To inform this issue, we sought to determine the frequency and underlying causes of potentially preventable ICU readmissions.

Design:

Retrospective cohort study.

Setting:

Urban, academic medical center in the mid-Atlantic United States.

Patients:

Adult patients discharged alive from their first ICU admission with an unplanned readmission within 48 hours of discharge.

Measurements and Main Results:

Each patient’s medical chart was reviewed by two independent investigators who rated each readmission’s preventability according to standardized scale and assessed the etiology of both preventable and nonpreventable readmissions. We assessed concordance between raters using the κ statistic and resolved disagreements through iterative discussion. Of 136 readmissions in the final analysis, 16 (11.8%; 95% CI, 6.9–18.4) were considered preventable and 120 (88.2%; 95% CI, 81.5–93.1) were considered nonpreventable. Of nonpreventable readmissions, 67 were due to a new clinical problem and 53 were due to an existing clinical problem. Among preventable readmissions, six were attributable to system errors, six were attributable to management errors, two were attributable to procedural events, one was attributable to a diagnostic error, and one was attributable to a medication error. Compared to nonpreventable readmissions, preventable readmissions tended to have shorter index ICU lengths of stay (2 vs 3 d; p = 0.05) and a shorter duration of time on the ward prior to readmission (16.6 vs 23.6 hr; p = 0.05).

Conclusions:

The majority of early ICU readmissions are nonpreventable, raising important concerns about ICU readmission rates as a measure of hospital performance.
Coping as a Multifaceted Construct: Associations With Psychological Outcomes Among Family Members of Mechanical Ventilation Survivors
Authors: Nadig Nandita , Huff Nidhi G. , Cox Christopher E. , Ford Dee W.
Published: April 2016

Objectives:

To develop and evaluate a preliminary multifaceted model for coping among family members of patients who survive mechanical ventilation.

Design and Setting:

In this multicenter cross-sectional survey, we interviewed family members of mechanically ventilated patients at the time of transfer from the ICU to the hospital ward. We constructed a theoretic model of coping that included characteristics attributable to family members, family-clinician rapport, and patients. We then explored relationships between coping factors and symptoms of psychological distress (anxiety, depression, and posttraumatic stress).

Subjects:

Fifty-six family members of survivors of mechanical ventilation.

Measurements and Main Results:

Psychological distress measured by the Hospital Anxiety and Depression Scale and Posttraumatic Stress Scale. Optimism measured using the Life Orientation Test scale, resiliency by Conner-Davidson Resilience Scale, and social support using the Patient Reported Outcomes Measurement Information System inventory. Family members had moderate levels of psychological distress with median total Hospital Anxiety and Depression Scale equal to 14 (interquartile range, 5–20) and Posttraumatic Stress Scale equal to 22 (interquartile range, 15–31). Among family member characteristics, greater optimism (p = 0.001, Hospital Anxiety and Depression Scale; p = 0.010, Posttraumatic Stress Scale), resilience (p = 0.012, Hospital Anxiety and Depression Scale), and social support (p = 0.013, Hospital Anxiety and Depression Scale) were protective against psychological distress. On the contrary, characteristics of family-clinician rapport such as communication quality and presence of conflict did not have any associations with psychological distress.

Conclusion:

To our knowledge, this is the first study to explore coping as a multifaceted construct and its relationship with family psychological outcomes among survivors of mechanical ventilation. We found certain family characteristics of coping such as optimism, resilience, and social support to be associated with less psychological distress. Further research is warranted to identify potentially modifiable aspects of coping that might guide future interventions.
Predicting Performance Status 1 Year After Critical Illness in Patients 80 Years or Older: Development of a Multivariable Clinical Prediction Model
Authors: Heyland Daren K. , Stelfox Henry T. , Garland Allan , Cook Deborah , Dodek Peter , Kutsogiannis Jim , Jiang Xuran , Turgeon Alexis F. , Day Andrew G.
Published: April 2016

Objective:

We sought to develop and internally validate a clinical prediction model to estimate the outcome of very elderly patients 12 months after being admitted to the ICU.

Design:

Prospective, longitudinal cohort study.

Setting:

Twenty-two Canadian ICUs.

Patients:

We recruited 527 patients 80 years or older who had a medical or urgent surgical diagnosis and were admitted to an ICU for at least 24 hours.

Measurements and Main Results:

At baseline, we completed a comprehensive geriatric assessment of enrolled patients; survival and functional status was determined 12 months later. We defined recovery from critical illness as Palliative Performance Scale score of greater than or equal to 60. We used logistic regression analysis to examine factors associated with this outcome. Of the 434 patients (82%) whose Palliative Performance Scale was known at 12 months, 50% had died and 29% (126/434) had a score of greater than or equal to 60. In the multivariable model, we found that being married, having a primary diagnosis of emergency coronary artery bypass grafting or valve replacement, and higher baseline Palliative Performance Scale were independently predictive of a 12-month Palliative Performance Scale score of greater than or equal to 60. Male sex, primary diagnosis of stroke, and higher Acute Physiology and Chronic Health Evaluation II score, Charlson comorbidity index, or clinical frailty scale were independently predictive of Palliative Performance Scale score of less than 60.

Conclusion:

Approximately one-quarter of very old ICU patients achieve a reasonable level of function 1 year after admission. This prediction model applied to individual patients may be helpful in decision making about the utility of life support for very elderly patients who are admitted to the ICU.
Operating Room Delays
Authors: Van Winkle Rachelle A. , Champagne Mary T. , Gilman-Mays Meri , Aucoin Julia
Published: April 2016

Perioperative areas are the most costly to operate and account for more than 40% of expenses. The high costs prompted one organization to analyze surgical delays through a retrospective review of their new electronic health record. Electronic health records have made it easier to access and aggregate clinical data; 2123 operating room cases were analyzed. Implementing a new electronic health record system is complex; inaccurate data and poor implementation can introduce new problems. Validating the electronic health record development processes determines the ease of use and the user interface, specifically related to user compliance with the intent of the electronic health record development. The revalidation process after implementation determines if the intent of the design was fulfilled and data can be meaningfully used. In this organization, the data fields completed through automation provided quantifiable, meaningful data. However, data fields completed by staff that required subjective decision making resulted in incomplete data nearly 24% of the time. The ease of use was further complicated by 490 permutations (combinations of delay types and reasons) that were built into the electronic health record. Operating room delay themes emerged notwithstanding the significant complexity of the electronic health record build; however, improved accuracy could improve meaningful data collection and a more accurate root cause analysis of operating room delays. Accurate and meaningful use of data affords a more reliable approach in quality, safety, and cost-effective initiatives.
Usability Assessment of Moodle by Brazilian and Portuguese Nursing Students
Authors: Seixas Carlos Alberto , de Godoy Simone , Martins JoséÉ Carlos Amado , Mazzo Alessandra , Baptista Rui Carlos Negrão , Mendes Isabel Amélia Costa
Published: April 2016

Distance education has turned into an important tool for nursing education. The virtual learning environments contribute toward an interactive and attractive educational process. In this study, we assess the usability of a virtual learning environment that was developed to teach nursing students how to care for patients with urinary retention. A multicenter and descriptive study was undertaken, which involved nursing students from the University of São Paulo at Ribeirão Preto College of Nursing, Brazil, and the Escola Superior de Enfermagem de Coimbra, Portugal. The participants were 79 students, mostly female, between 20 and 24 years of age. The virtual learning environment revealed good properties in terms of usability on most criteria. Future research will help to confirm the results.
Bullous pemphigoid, an autoantibody-mediated disease, is a novel immune-related adverse event in patients treated with anti-programmed cell death 1 antibodies
Authors: Hwang Shelley J.E. , Carlos Giuliana , Chou Shaun , Wakade Deepal , Carlino Matteo S. , Fernandez-Penas Pablo
Published: April 2016

Anti-programmed cell death 1 (anti-PD1) antibodies such as pembrolizumab have shown improved progression-free and overall survival in patients with advanced melanoma. Of 124 patients reviewed in Westmead Hospital from May 2012 to November 2015, treated with pembrolizumab for advanced melanoma, we encountered three cases of bullous pemphigoid (BP). We have previously reported a case of BP. In two recent cases, BP was diagnosed early and treated promptly with potent topical or oral steroid. Patients on anti-PD1 antibodies are at a higher risk of developing cutaneous immune-related adverse events such as lichenoid reactions, eczema and vitiligo. No cases of BP were encountered in the previously published cohort of 260 melanoma patients treated with BRAF inhibitors; as such, it appears that BP is associated with anti-PD1 treatment rather than metastatic melanoma. BP appears to be another immune-related adverse event, and clinicians should have a low threshold for performing cutaneous biopsies and immunofluorescence studies in patients on anti-PD1 therapies.
Ipilimumab-induced acute generalized exanthematous pustulosis in a patient with metastatic melanoma
Authors: Hwang Shelley J.E. , Carlos Giuliana , Wakade Deepal , Sharma Raghwa , Fernandez-Penas Pablo
Published: April 2016

Ipilimumab is a new anti-cytotoxic T-lymphocyte antigen-4 monoclonal antibody that stimulates the immune response against melanoma. A 50-year-old man received ipilimumab for metastatic melanoma as part of a clinical trial. Two weeks after drug initiation, he developed a widespread oedematous erythema with sterile pustules. The histological examination showed subcorneal pustulosis formation with eosinophils. The clinical–pathological correlation was consistent with acute generalized exanthematous pustulosis. The symptoms resolved within 25 days after discontinuation of ipilimumab. We suspect that neutrophilic accumulation under the epidermis in this patient is a phenomenon similar to intraepithelial neutrophils aggregating on the surface epithelium over laminar propria in ipilimumab-induced colitis. To our knowledge, this is the first reported case of acute generalized exanthematous pustulosis associated with ipilimumab use in metastatic melanoma patients.
Clinical Significance of International Union Against Cancer pN Staging and Lymph Node Ratio in Node-Positive Colorectal Cancer after Advanced Lymph Node Dissection
Authors: Märkl Bruno , Olbrich Georg , Schenkirsch Gerhard , Kretsinger Hallie , Kriening Bernadette , Anthuber Matthias
Published: April 2016

BACKGROUND:

Lymph node retrieval in colorectal cancer can be improved by using advanced histopathological techniques like methylene blue-assisted lymph node dissection, which results in a doubling or even tripling of the lymph node count in comparison with conventional lymph node dissection techniques. However, it is not clear whether the established lymph node staging systems are suitable for predicting patients’ prognoses under these circumstances.

OBJECTIVE:

The aim of this study was to determine whether the current lymph node staging systems are suitable when advanced dissection methods are used.

DESIGN:

This is a retrospective cohort study.

SETTING AND PATIENTS:

We formed a study group (methylene blue-assisted lymph node dissection) of 293 patients and a control group (conventional lymph node dissection) of 232 patients, each with node-positive cases. Conventional pN staging according to the International Union Against Cancer, seventh edition, and lymph node ratio were applied.

MAIN OUTCOME MEASURES:

Overall survival was compared by using the different staging systems in a uni- and multivariable fashion.

RESULTS:

The lymph node ratio values were reduced in the advanced methylene blue-assisted lymph node dissection group in comparison with the conventional lymph node dissection group (0.1 vs 0.3, p < 0.001). Although pN staging proved to be reliable, the cutoff values for lymph node ratio staging had to be adapted. The new cutoffs (0.07, 0.15, and 0.34) were prognostic. However, multivariable analysis revealed pN staging and vascular invasion, but not lymph node ratio, as independently prognostic in the methylene blue-assisted lymph node dissection group.

LIMITATIONS:

The study group and historical control group are not perfectly balanced because the case number in the stage III subgroup of the control group is small.

CONCLUSIONS:

pN staging proved to be a robust prognostic marker in colorectal cancer under the circumstances of improved lymph node harvest. After adaptation of the cutoff values, lymph node ratio is also prognostic but not superior to pN staging.
The relationship between aggression, empathy skills and serum oxytocin levels in male children and adolescents with attention deficit and hyperactivity disorder
Authors: Demirci Esra , Ozmen Sevgi , Kilic Eser , Oztop Didem B.
Published: April 2016

Although attention deficit and hyperactivity disorder (ADHD) are recognized as neurodevelopmental disorders characterized by impairment in executive functions, impairments in social functioning are often accompanied by ADHD. Oxytocin (OT) has been investigated in a number of psychiatric disorders owing to its effects on social interactions. The aim of this study was to determine the relationship between aggression, empathy and OT levels in children with ADHD. Forty male patients with ADHD, ranging in age from 7 to 18 years, and 40 healthy age-matched and sex-matched individuals were included in this study. The patients and healthy controls filled in the Buss–Perry Aggression Questionnaire and Bryant’s Empathy Index for Children and Adolescents; the Reading the Mind in the Eyes test was then completed. Blood samples were collected for OT at the beginning of the study. Lower serum OT levels were observed in patients with ADHD compared with the healthy controls. Moreover, there was a negative correlation between serum OT level and aggression scores and a positive correlation between the serum OT level and empathy scores in patients with ADHD. We conclude that OT may play a role in aggression and empathy skills, affecting the social life of those with ADHD.
Effect of ketamine administration, alone and in combination with E-6837, on climbing behavior
Authors: Briones-Aranda Alfredo , Suárez-Santiago José E. , Picazo Ofir , Castellanos-Pérez Manuela
Published: April 2016

Some types of schizophrenia have been associated with repetitive movements lacking specific purpose, also known as stereotyped behavior. Dopamine agonists (D2) and noncompetitive N-methyl-d-aspartate receptor antagonists (e.g. ketamine) have been administered in rodent models to induce stereotyped behavior that resembles some motor symptoms of schizophrenia. Recently, a relationship has been found between 5-HT6 receptors (5-HT6Rs) and dopaminergic activity. The present study evaluates the effect of ketamine (5 and 10 mg/kg), alone and in combination with the 5-HT6R agonist E-6837, on the climbing behavior of male mice. Ketamine was administered with an acute (1 day) and subchronic (5 day) scheme. Later, these doses and schemes were combined with an acute scheme of E-6837 (5 and 10 mg/kg). With both the acute and the subchronic schemes, ketamine increased climbing behavior at a dose of 10 mg/kg, and this effect was reversed by E-6837 (at 5 and 10 mg/kg). The present results suggest that there is an interaction between N-methyl-d-aspartate and 5-HT6 receptors in the regulation of climbing behavior. Further research is necessary to provide more evidence on this interaction.
Locomotor, discriminative stimulus, and place conditioning effects of MDAI in rodents
Authors: Gatch Michael B. , Dolan Sean B. , Forster Michael J.
Published: April 2016

5,6-Methylenedioxy-2-aminoindane (MDAI) has become a common substitute for (±)-3,4-methylenedioxymethamphetamine (MDMA) in Ecstasy. MDAI is known to produce MDMA-like discriminative stimulus effects, but it is not known whether MDAI has psychostimulant or hallucinogen-like effects. MDAI was tested for locomotor stimulant effects in mice and subsequently for discriminative stimulus effects in rats trained to discriminate cocaine (10 mg/kg, intraperitoneally), methamphetamine (1 mg/kg, intraperitoneally), ±MDMA (1.5 mg/kg, intraperitoneally), or (−)-2,5-dimethoxy-4-methylamphetamine hydrochloride (0.5 mg/kg, intraperitoneally) from saline. The ability of MDAI to produce conditioned place preference was also tested in mice. MDAI (3 to 30 mg/kg) depressed locomotor activity from 10 to 60 min. A rebound stimulant effect was observed at 1 to 3.5 h following 30 mg/kg. Lethality occurred in 8/8 mice following 100 mg/kg MDAI. Similarly, MDMA depressed locomotor activity immediately following the administration of 0.25 mg/kg and stimulant effects were observed 50–70 min following the administration of 0.5 and 1 mg/kg. MDAI fully substituted for the discriminative stimulus effects of MDMA (2.5 mg/kg), (−)-2,5-dimethoxy-4-methylamphetamine hydrochloride (5 mg/kg), and cocaine (7.5 mg/kg), but produced only 73% methamphetamine-appropriate responding at a dose that suppressed responding (7.5 mg/kg). MDAI produced tremors at 10 mg/kg in one methamphetamine-trained rat. MDAI produced conditioned place preference from 0.3 to 10 mg/kg. The effects of MDAI on locomotor activity and drug discrimination were similar to those produced by MDMA, having both psychostimulant-like and hallucinogen-like effects; thus, MDAI may have similar abuse potential as MDMA.
Antihyperalgesic effect of [(±)-(2,4,6-cis)-4-chloro-6-(naphthalen-1-yl)-tetrahydro-2H-pyran-2-yl]methanol: participation of the NO/cGMP/KATP pathway and κ-opioid receptor
Authors: Gonçalves Gabriela M. , Capim Saulo L. , Vasconcellos Mário L.A.A. , Marinho Bruno G.
Published: April 2016

The present study used behavioral analyses to investigate the involvement of the NO/cGMP/KATP pathway, serotoninergic, and opioid systems in the antinociceptive action of [(±)-(2,4,6-cis)-4-chloro-6-(naphthalen-1-yl)-tetrahydro-2H-pyran-2-yl]methanol (CTHP) in mice. Oral administration of CTHP (1, 5, 10, and 30 mg/kg) exerted effects at higher doses in chemical models of nociception (the acetic acid writhing and formalin tests) as well as a thermal model (the tail-flick test). It was also found that pretreatment with l-NG-nitroarginine methyl ester (nonselective nitric oxide synthase inhibitor), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (selective inhibitor of nitric oxide-sensitive guanosyl cyclase), glibenclamide (selective ATP-sensitive K+ channel blocker), naloxone (nonselective opioid receptor blocker), and nor-binaltorphimine (selective κ-opioid receptor blocker), but not methylnaltrexone (peripheral μ-opioid receptor blocker) or naltrindole (selective δ-opioid receptor blocker), reversed the antinociceptive effect of CTHP. In addition, CTHP induced the development of tolerance in the tail-flick test: the tolerance appeared later compared with morphine, and was only observed with a higher dose. Taken together, the present study showed that the systemic administration of CTHP reduced pain induced by chemical and thermal stimuli. We also suggest that the possible mechanisms include the involvement of the NO/cGMP/KATP pathway and the κ-opioid receptor.
Altered KATP Channel Subunits Expression and Vascular Reactivity in Spontaneously Hypertensive Rats With Age
Authors: Liu Xiaojing , Duan Peng , Hu Xingxing , Li Ruisheng , Zhu Qinglei
Published: April 2016

ATP-sensitive potassium (KATP) channels link membrane excitability to metabolic state to regulate a series of biological activities including the vascular tone. However, their ability to influence hypertension is controversial. Here we aim to investigate possible alteration of KATP channel in vascular smooth muscles (VSMs) during hypertension development process. In this study, we used 16-week-old spontaneously hypertensive rats (SHRs), 49-week-old SHRs, and their age-matched Wistar-Kyoto rats to study the expression of VSM KATP subunits at the mRNA and protein level and the function of VSM KATP by observing the relaxation reactivity of isolated aorta rings to KATP modulators. We found that the expression of VSM KATP subunits Kir6.1 and sulfonylurea receptor (SUR2B) decreased during hypertension. Moreover, the expression of SUR2B and Kir6.1 in 49-week-old SHRs decreased much more than that in 16-week-old SHRs. Furthermore, the aorta rings of 49-week-old SHRs showed lower reactivity to diazoxide than 16-week-old SHRs. This study suggests that KATP channels in VSM subunits Kir6.1 and SUR2B contribute to modify the functionality of this channel in hypertension with age.
Combination Therapy With Coenzyme Q10 and Trimetazidine in Patients With Acute Viral Myocarditis
Authors: Shao Liang , Ma Aiqun , Figtree Gemma , Zhang Ping
Published: April 2016

Background:

Acute viral myocarditis is an inflammatory disease with global impact. Although it may resolve spontaneously, its course is not easily predicted, and there is a paucity of specific treatment options available with proven efficacy. Coenzyme Q10 (CQ10) and trimetazidine possess antioxidant and antiinflammatory effects.

Methods:

We examined the therapeutic efficacy of these agents in acute viral myocarditis both individually and in combination. Patients were blinded and randomized to receive CQ10 (n = 42), trimetazidine (n = 39), or CQ10 + trimetazidine (n = 43) treatment.

Results:

Serum inflammatory and oxidative stress marker and myocardial enzyme levels, and heart function were measured. Both CQ10 and trimetazidine decreased inflammatory and oxidative stress biomarker levels compared with baseline measurements. However, combination therapy with CQ10 and trimetazidine showed a significantly more powerful effect not only on markers of inflammation and oxidative stress, but also on left ventricular systolic function and troponin, compared with either treatment alone.

Conclusion:

This study confirmed the beneficial effect of CQ10 and trimetazidine individually, but demonstrated a superior effect of combining the therapies on cardiac left ventricular ejection fraction, and biochemical markers of myocardial damage in acute viral myocarditis.
Genetic Predisposition to Poor Opioid Response in Preterm Infants: Impact of KCNJ6 and COMT Polymorphisms on Pain Relief After Endotracheal Intubation
Authors: Elens Laure , Norman Elisabeth , Matic Maja , Rane Anders , Fellman Vineta , van Schaik Ron H. N.
Published: April 2016

Background:

Single-nucleotide polymorphisms in genes involved in pain control might predispose to exaggerated sensitivity or difference in opioid analgesic effect. The relevance of the KCNJ6 -1250G>A (rs6517442, c.-1787G>A) and the catecholamine-O-methyltransferase (COMT) c.472G>A (rs4680, Val158Met) single-nucleotide polymorphisms were studied in preterm infants needing intubation and randomized to a premedication strategy including remifentanil (n = 17) or morphine (n = 17).

Methods:

Pain was scored with Astrid Lindgren and Lund Children's Hospital Pain Assessment Scale every 30 minutes for 6 hours. The pain relief provided by the opioids was compared between the different KCNJ6 and COMT genotypes.

Results:

Infants homozygous for the KCNJ6 -1250A allele had an increased duration after intubation to achieve a score indicating no pain compared with infants with the A/G or G/G genotypes (182 ± 30, 109 ± 29, and 60 ± 21 minutes, respectively; Logrank = 7.5, P = 0.006). Similarly, the duration was increased in individuals with the COMT Val/Val alleles compared with Val/Met and Met/Met (285 ± 37, 137 ± 25, and 63 ± 15 minutes, respectively; Logrank = 14.4, P = 0.0021). Cox proportional hazards analysis confirmed that the variation in both genes was independently associated with susceptibility to respond to therapy.

Conclusion:

We conclude that the KCNJ6 -1250A and COMT
158Val alleles are predisposing preterm newborns to diminished opioid-induced pain relief.
Effects of ospemifene on bone parameters including clinical biomarkers in postmenopausal women
Authors: Constantine Ginger D. , Kagan Risa , Miller Paul D.
Published: April 2016

Objective:

Ospemifene is an estrogen-receptor agonist/antagonist (also known as a selective estrogen-receptor modulator) that is FDA approved for the treatment of moderate-to-severe dyspareunia, a symptom of vulvovaginal atrophy, due to menopause. Preclinical and clinical data suggest that ospemifene may also have an effect on bone health in postmenopausal women.

Methods:

Relevant articles, including cellular and preclinical studies and clinical trials written in English pertaining to ospemifene and bone health, were identified from a database search of PubMed (from its inception to June 2015) and summarized in this comprehensive review.

Results:

In vitro data suggest that ospemifene may mediate a positive effect on bone through osteoblasts. Ospemifene effectively reduced bone loss and resorption in ovariectomized rats, with activity comparable to estradiol and raloxifene. Clinical data from three phase 1 or 2 clinical trials (2 placebo- and 1 raloxifene-controlled) found ospemifene 60 mg/d to have a positive effect on the biochemical markers for bone turnover in healthy, postmenopausal women with significant improvements relative to placebo and comparable to raloxifene.

Conclusions:

Ospemifene 60 mg/d may have a protective effect on the bone health of women being treated for dyspareunia. The initial clinical data for ospemifene follows a trend similar to raloxifene and bazedoxifene, suggesting that ospemifene may have bone-protective effects in postmenopausal women. However, additional rigorous clinical trials are necessary to confirm any positive effects ospemifene may have on vertebral fractures and bone mineral density in healthy and osteoporotic women.
No-drain DIEP Flap Donor-site Closure Using Barbed Progressive Tension Sutures
Authors: Nagarkar Purushottam , Lakhiani Chrisovalantis , Cheng Angela , Lee Michael , Teotia Sumeet , Saint-Cyr Michel
Published: April 2016

Background:

The use of progressive tension sutures has been shown to be comparable to the use of abdominal drains in abdominoplasty. However, the use of barbed progressive tension sutures (B-PTSs) in deep inferior epigastric artery perforator (DIEP) flap donor-site closure has not been investigated.

Methods:

A retrospective chart review was performed on patients with DIEP flap reconstruction in a 3-year period at 2 institutions by 2 surgeons. Patients were compared by method of DIEP donor-site closure. Group 1 had barbed running progressive tension sutures without drain placement. Group 2 had interrupted progressive tension closure with abdominal drain placement (PTS-AD). Group 3 had closure with only abdominal drain placement (AD). Data collected included demographics, perioperative data, and postoperative outcomes.

Results:

Seventy-five patients underwent DIEP reconstruction (25 B-PTS, 25 PTS-AD, and 25 AD). Patient characteristics—age, body mass index, comorbidities, smoking status, and chemotherapy—were not significantly different between groups. Rate of seroma was 1.3% (B-PTS = 0%, PTS-AD = 4%, AD = 0%), wound dehiscence 16% (B-PTS = 8%, PTS-AD = 16%, AD = 24%), and umbilical necrosis 5.3% (B-PTS = 0%, PTS-AD = 0%, AD = 16%). No hematomas were observed in any patients. No statistically significant difference was found between complication rates across groups.

Conclusions:

Use of B-PTSs for abdominal closure after DIEP flap harvest can obviate the need for abdominal drains. Complication rates following this technique are not significantly different from closure using progressive tension suture and abdominal drain placement. This practice can prevent the use of abdominal drains, which can promote patient mobility, increase independence upon discharge, and contribute to patient satisfaction.
Scalp Medical Tattooing Technique to Camouflage Bifid Parietal Whorls
Authors: Park Jae Hyun , You Seung Hyun
Published: April 2016

Background:

To the best of the authors’ knowledge, no reports have described cosmetic problems arising from the hair direction around the parietal whorl (PW). This study was performed to evaluate the efficacy of scalp medical tattooing technique for camouflaging bifid PWs.

Methods:

We retrospectively examined the outcomes of scalp medical tattooing in 38 patients who were admitted for camouflage of a bifid PW.

Results:

All patients’ cosmetic appearance was judged, by both the patients and the surgeon, to be markedly improved. No specific complications occurred, such as infection, hair loss in the operative field, or other problems.

Conclusion:

Scalp medical tattooing appears to be an effective method that helps to camouflage the see-through appearance of bifid PWs.
Lateral Approach to the Popliteal Artery for Free Tissue Transfer to the Lower Extremity
Authors: Sinkin Jeremy C. , Rudolph Megan , Akbari Cameron , Evans Karen F. Kim
Published: April 2016

Free tissue transfer to the proximal leg and knee requires appropriate recipient vessel selection. The popliteal vessels have historically been unpopular choices, due to their remote location often necessitating vein grafts, and need for prone positioning. In this report, we describe a lateral approach to the above-knee popliteal vessels, which was utilized for 2 cases of free tissue transfer to the lower extremity. Neither prone positioning nor vein grafts were needed. The lateral approach to the above-knee popliteal vessels and their branches is a viable option for the otherwise recipient vessel-depleted lower extremity.