bluuebunny/crossref_metadata_2025 huggingface dataset:
Derivation of Novel Risk Prediction Scores for Community-Acquired Sepsis and Severe Sepsis*
Authors: Wang Henry E. , Donnelly John P. , Griffin Russell , Levitan Emily B. , Shapiro Nathan I. , Howard George , Safford Monika M.
Published: April 2016

Objective:

We sought to derive and internally validate a Sepsis Risk Score and a Severe Sepsis Risk Score predicting future sepsis and severe sepsis events among community-dwelling adults.

Design:

National population-based cohort.

Setting:

United States.

Subjects:

A total of 30,239 community-dwelling adults 45 years old or older in the national REasons for Geographic And Racial Differences in Stroke cohort.

Interventions:

None.

Measurements and Main Results:

Over a median of 6.6 years (interquartile range, 5.1–8.1 yr) of follow-up, there were 1,532 first sepsis (prevalence 8.3 per 1,000 person-years) and 1,151 first severe sepsis (6.2 per 1,000 person-years) events. Risk factors in the best derived Sepsis Risk Score and Severe Sepsis Risk Score included chronic lung disease, age 75 years or older, peripheral artery disease, diabetes, tobacco use, white race, stroke, atrial fibrillation, coronary artery disease, obesity, hypertension, deep vein thrombosis, male sex, high-sensitivity C-reactive protein greater than 3.0 mg/dL, cystatin C ≥1.11 mg/dL, estimated glomerular filtration rate less than 60 mL/min/1.73 m2, and albumin-to-creatinine ratio protein greater than 30 μg/mg. Sepsis Risk Score risk categories were very low (0–3 points; 2.3 events per 1,000 person-years), low (4–6; 4.1), medium (7–9; 6.5), high (10–12; 9.7), and very high (13–38; 21.1). Severe Sepsis Risk Score risk categories were very low (0–5 points; 1.5 events per 1,000 person-years), low (6–9; 3.4), medium (10–13; 6.7), high (14–17; 9.9), and very high (18–45; 22.1). The Sepsis Risk Score and Severe Sepsis Risk Score exhibited good discrimination (bootstrapped C index, 0.703 and 0.742) and calibration (p = 0.65 and 0.06).

Conclusions:

The Sepsis Risk Score and Severe Sepsis Risk Score predict 10-year sepsis and severe sepsis risk among community-dwelling adults and may aid in sepsis prevention or mitigation efforts.
Osmotherapy With Hypertonic Saline Attenuates Global Cerebral Edema Following Experimental Cardiac Arrest via Perivascular Pool of Aquaporin-4
Authors: Nakayama Shin , Migliati Elton , Amiry-Moghaddam Mahmood , Ottersen Ole P. , Bhardwaj Anish
Published: April 2016

Objectives:

We tested the hypothesis that osmotherapy with hypertonic saline attenuates cerebral edema following experimental cardiac arrest and cardiopulmonary resuscitation by exerting its effect via the perivascular pool of aquaporin-4. We used mice with targeted disruption of the gene encoding α-syntrophin (α-Syn–/–) that demonstrate diminished perivascular aquaporin-4 pool but retain the non-endfoot and ependymal pools.

Design:

Laboratory animal study.

Setting:

University animal research laboratory.

Interventions:

Isoflurane-anesthetized adult male wild-type C57B/6 or α-Syn–/– mice were subjected to cardiac arrest/cardiopulmonary resuscitation and treated with either a continuous IV infusion of 0.9% saline or various concentrations of hypertonic saline. Serum osmolality, regional brain water content, blood-brain barrier disruption, and aquaporin-4 protein expression were determined at 24 hours after cardiac arrest/cardiopulmonary resuscitation.

Measurements and Main Results:

Hypertonic saline (7.5%) treatment significantly attenuated water content in the caudoputamen complex and cortex compared with 0.9% saline treatment in wild-type mice subjected to cardiac arrest/cardiopulmonary resuscitation. In contrast, in α-Syn–/– mice subjected to cardiac arrest/cardiopulmonary resuscitation, 7.5% hypertonic saline treatment did not attenuate water content. Treatment with 7.5% hypertonic saline attenuated blood-brain barrier disruption at 24 hours following cardiac arrest/cardiopulmonary resuscitation in wild-type mice but not in α-Syn–/– mice. Total aquaporin-4 protein expression was not different between 0.9% saline and hypertonic saline–treated wild-type mice.

Conclusions:

Following experimental cardiac arrest/cardiopulmonary resuscitation: 1) continuous hypertonic saline therapy maintained to achieve serum osmolality of ≈ 350 mOsm/L is beneficial for the treatment of cerebral edema; 2) perivascular pool of aquaporin-4 plays a critical role in water egress from brain; and 3) hypertonic saline attenuates blood-brain barrier disruption via perivascular aquaporin-4 pool.
Real-Time Risk Prediction on the Wards: A Feasibility Study
Authors: Kang Michael A. , Churpek Matthew M. , Zadravecz Frank J. , Adhikari Richa , Twu Nicole M. , Edelson Dana P.
Published: April 2016

Objective:

Failure to detect clinical deterioration in the hospital is common and associated with poor patient outcomes and increased healthcare costs. Our objective was to evaluate the feasibility and accuracy of real-time risk stratification using the electronic Cardiac Arrest Risk Triage score, an electronic health record-based early warning score.

Design:

We conducted a prospective black-box validation study. Data were transmitted via HL7 feed in real time to an integration engine and database server wherein the scores were calculated and stored without visualization for clinical providers. The high-risk threshold was set a priori. Timing and sensitivity of electronic Cardiac Arrest Risk Triage score activation were compared with standard-of-care Rapid Response Team activation for patients who experienced a ward cardiac arrest or ICU transfer.

Setting:

Three general care wards at an academic medical center.

Patients:

A total of 3,889 adult inpatients.

Measurements and Main Results:

The system generated 5,925 segments during 5,751 admissions. The area under the receiver operating characteristic curve for electronic Cardiac Arrest Risk Triage score was 0.88 for cardiac arrest and 0.80 for ICU transfer, consistent with previously published derivation results. During the study period, eight of 10 patients with a cardiac arrest had high-risk electronic Cardiac Arrest Risk Triage scores, whereas the Rapid Response Team was activated on two of these patients (p < 0.05). Furthermore, electronic Cardiac Arrest Risk Triage score identified 52% (n = 201) of the ICU transfers compared with 34% (n = 129) by the current system (p < 0.001). Patients met the high-risk electronic Cardiac Arrest Risk Triage score threshold a median of 30 hours prior to cardiac arrest or ICU transfer versus 1.7 hours for standard Rapid Response Team activation.

Conclusions:

Electronic Cardiac Arrest Risk Triage score identified significantly more cardiac arrests and ICU transfers than standard Rapid Response Team activation and did so many hours in advance.
Endothelial Activation and Blood-Brain Barrier Injury as Risk Factors for Delirium in Critically Ill Patients*
Authors: Hughes Christopher G. , Pandharipande Pratik P. , Thompson Jennifer L. , Chandrasekhar Rameela , Ware Lorraine B. , Ely E. Wesley , Girard Timothy D.
Published: April 2016

Objectives:

During critical illness, impaired endothelial vascular reactivity predicts prolonged acute brain dysfunction, but relationships between endothelial activation, blood-brain barrier/neurological injury, and acute brain dysfunction, including delirium, remain unexamined. We tested the hypothesis that elevated plasma markers of endothelial activation and blood-brain barrier/neurological injury are associated with delirium duration during critical illness.

Design:

Prospective cohort study.

Setting:

Medical and surgical ICUs in an academic medical center.

Patients:

Adults in acute respiratory failure and/or shock.

Interventions:

None.

Measurements and Main Results:

We enrolled subjects within 72 hours of organ failure diagnosis in the ICU. We measured plasma concentrations of plasminogen activator inhibitor-1, E-selectin, and angiopoietin-2 as markers of endothelial activation and S100B as a marker of blood-brain barrier/neurological injury in blood collected at enrollment. We assessed patients for delirium and coma twice daily after enrollment using the Confusion Assessment Method for the ICU and the Richmond Agitation-Sedation Scale. Among 134 patients with a median (interquartile) age of 57 years (46–66 yr) and Acute Physiology and Chronic Health Evaluation II of 26 (19–31), delirium occurred in 94 patients (70%) with a median duration of 2 days (0–4 d). Higher plasminogen activator inhibitor-1 (p = 0.002), E-selectin (p = 0.02), and S100B (p < 0.001) concentrations were associated with fewer delirium/coma-free days after adjusting for age, Charlson comorbidity index, modified Sequential Organ Failure Assessment score, and severe sepsis. Similarly, higher plasminogen activator inhibitor-1 (p = 0.007) and S100B (p = 0.01) concentrations were associated with longer delirium duration in survivors. Adjusting for S100B did not alter plasminogen activator inhibitor-1 and E-selectin associations with delirium, suggesting that these associations were not mediated by blood-brain barrier/neurological injury.

Conclusions:

Elevated plasma markers of endothelial activation and blood-brain barrier/neurological injury during critical illness are associated with prolonged delirium after biomarker measurement. Future research is needed to determine whether these processes have pathophysiologic roles in delirium and whether therapies targeted at the endothelium or blood-brain barrier can prevent and/or treat delirium during critical illness.
Effects of Blended Cardiopulmonary Resuscitation and Defibrillation E-learning on Nursing Students’ Self-efficacy, Problem Solving, and Psychomotor Skills
Authors: Park Ju Young , Woo Chung Hee , Yoo Jae Yong
Published: April 2016

This study was conducted to identify the educational effects of a blended e-learning program for graduating nursing students on self-efficacy, problem solving, and psychomotor skills for core basic nursing skills. A one-group pretest/posttest quasi-experimental design was used with 79 nursing students in Korea. The subjects took a conventional 2-week lecture-based practical course, together with spending an average of 60 minutes at least twice a week during 2 weeks on the self-guided e-learning content for basic cardiopulmonary resuscitation and defibrillation using Mosby’s Nursing Skills database. Self- and examiner-reported data were collected between September and November 2014 and analyzed using descriptive statistics, paired t test, and Pearson correlation. The results showed that subjects who received blended e-learning education had improved problem-solving abilities (t = 2.654) and self-efficacy for nursing practice related to cardiopulmonary resuscitation and defibrillation (t = 3.426). There was also an 80% to 90% rate of excellent postintervention performance for the majority of psychomotor skills, but the location of chest compressions, compression rate per minute, artificial respiration, and verification of patient outcome still showed low levels of performance. In conclusion, blended E-learning, which allows self-directed repetitive learning, may be more effective in enhancing nursing competencies than conventional practice education.
Mapping Perinatal Nursing Process Measurement Concepts to Standard Terminologies
Authors: Ivory Catherine H.
Published: April 2016

The use of standard terminologies is an essential component for using data to inform practice and conduct research; perinatal nursing data standardization is needed. This study explored whether 76 distinct process elements important for perinatal nursing were present in four American Nurses Association–recognized standard terminologies. The 76 process elements were taken from a valid paper-based perinatal nursing process measurement tool. Using terminology-supported browsers, the elements were manually mapped to the selected terminologies by the researcher. A five-member expert panel validated 100% of the mapping findings. The majority of the process elements (n = 63, 83%) were present in SNOMED-CT, 28% (n = 21) in LOINC, 34% (n = 26) in ICNP, and 15% (n = 11) in CCC. SNOMED-CT and LOINC are terminologies currently recommended for use to facilitate interoperability in the capture of assessment and problem data in certified electronic medical records. Study results suggest that SNOMED-CT and LOINC contain perinatal nursing process elements and are useful standard terminologies to support perinatal nursing practice in electronic health records. Terminology mapping is the first step toward incorporating traditional paper-based tools into electronic systems.
Combined Cancer Immunotherapy Against Aurora Kinase A
Authors: Kaštánková Iva , Poláková Ingrid , Dušková Martina , Šmahel Michal
Published: April 2016

Aurora kinase A (AURKA) is a centrosomal protein that is overexpressed in a number of human malignancies and can contribute to tumor progression. As we used this protein as a target of DNA immunization, we increased its immunogenicity by the addition of the PADRE helper epitope and decreased its potential oncogenicity by mutagenesis of the kinase domain. For in vitro analysis of induced immune responses in mice, we identified the Aurka220–228nonapeptide representing an H-2Kbepitope. As DNA vaccination against the Aurka self-antigen by a gene gun did not show any antitumor effect, we combined DNA immunization with anti-CD25 treatment that depletes mainly regulatory T cells. Whereas 1 anti-CD25 dose injected before DNA vaccination did not enhance the activation of Aurka-specific splenocytes, 3 doses administered on days of immunizations augmented about 10-fold immunity against Aurka. However, an opposite effect was found for antitumor immunity—only 1 anti-CD25 dose combined with DNA vaccination reduced tumor growth. Moreover, the administration of 3 doses of anti-CD25 antibody alone accelerated tumor growth. Analysis of tumor-infiltrating cells showed that 3 anti-CD25 doses not only efficiently depleted regulatory T cells but also activated helper T cells and CD3−CD25+cells. Next, we found that blockade of the PD-1 receptor initiated 1 week after the first immunization was necessary for significant inhibition of tumor growth with therapeutic DNA vaccination against Aurka combined with depletion of CD25+cells. Our results suggest that combined cancer immunotherapy should be carefully evaluated to achieve the optimal antitumor effect.
Complete Pathological Response After Neoadjuvant Long-Course Chemoradiotherapy for Rectal Cancer and Its Relationship to the Degree of T3 Mesorectal Invasion
Authors: Wilkins Simon , Haydon Andrew , Porter Ian , Oliva Karen , Staples Margaret , Carne Peter , McMurrick Paul , Bell Stephen
Published: April 2016

BACKGROUND:

Many studies have shown significantly improved outcomes (reduced local recurrence and improved overall survival) for patients achieving a complete pathological response from neoadjuvant chemoradiotherapy.

OBJECTIVE:

This study aimed to document the complete pathological response rate and outcomes in patients receiving preoperative long-course chemoradiotherapy stratified for the extent of T3 mesorectal invasion measured on preoperative imaging.

DESIGN:

This is a retrospective study of prospectively collected data, of patients with rectal cancer in the Cabrini Monash University Department of Surgery colorectal neoplasia database, incorporating data from Cabrini Hospital and The Alfred Hospital, identifying patients entered between January 2010 and June 2014.

PATIENTS AND SETTINGS:

One hundred eighteen patients with T3 rectal cancer met the selection criteria for the study; 26 achieved complete pathological response (22%).

MAIN OUTCOME MEASURES:

Outcomes in terms of complete pathological response and oncological outcomes such as disease-free and overall survival were analyzed.

RESULTS:

Patients with complete pathological response had significantly less preoperative invasion than those with no complete pathological response (p < 0.001). Depth of invasion was the only variable associated with complete pathological response (p < 0.002), and the likelihood of complete pathological response decreased by 35% for every millimeter of invasion. Complete pathological response was associated with increased disease-free survival (p = 0.018) and a lower risk of cancer progression (p = 0.046). Depth of invasion was associated with an increased risk of death after surgery; HR increased by 1.07 (95% CI, 1.00–1.15) for each 1-mm increase in invasion.

LIMITATIONS:

This was a retrospective study with the usual limitations, although these were minimized through the use of a clinician-driven prospective database.

CONCLUSIONS:

The smaller the degree of T3 invasion, the higher the chance of achieving complete pathological response (up to 35%), which is associated with improved disease-free and overall survival. A higher complete pathological response rate is observed in early T3 disease in comparison with more extensive T3 invasion.
Persistent Asymptomatic Anastomotic Leakage After Laparoscopic Sphincter-Saving Surgery for Rectal Cancer: Can Diverting Stoma Be Reversed Safely at 6 Months?
Authors: Hain Elisabeth , Maggiori Léon , Manceau Gilles , Zappa Magaly , Prost à la Denise Justine , Panis Yves
Published: April 2016

BACKGROUND:

Anastomotic leakage after rectal cancer surgery raises the problem of the timing of diverting stoma reversal.

OBJECTIVE:

The purpose of this study was to assess whether stoma reversal can be safely performed at 6 months after laparoscopic sphincter-saving surgery for rectal cancer with total mesorectal excision in patients with persistent asymptomatic anastomotic leakage.

DESIGN:

This was a retrospective analysis of a prospective database.

SETTINGS:

The study was conducted at a tertiary colorectal surgery referral center.

PATIENTS:

All of the patients with anastomotic leakage were treated conservatively after sphincter-saving laparoscopic total mesorectal excision for rectal cancer.

MAIN OUTCOME MEASURES:

The main study measure was postoperative morbidity.

RESULTS:

A total of 110 (26%) of 429 patients who presented with anastomotic leakage and were treated conservatively were diagnosed only on CT scan (60 symptomatic (14%) and 50 asymptomatic (12%)). During follow up, 82 (75%) of 110 anastomotic leakages healed spontaneously after a mean delay of 16 ± 6 weeks (range, 4–30 weeks). Among these patients, 7 (9%) of 82 developed postoperative symptomatic pelvic sepsis after stoma reversal. Among the 28 patients remaining, 3 died during follow-up. The remaining 25 patients (23%) presented with persistent asymptomatic anastomotic leakage with chronic sinus >6 months after rectal surgery. Stoma reversal was performed in 19 asymptomatic patients, but 3 (16%) of 19 developed postoperative symptomatic pelvic sepsis after stoma reversal (3/19 vs 7/82 patients; p = 0.217), requiring a redo surgery with transanal colonic pull-through and delayed coloanal anastomosis (n = 2) or standard coloanal anastomosis (n = 1). Regarding the 6 final patients, abdominal redo surgery was performed because of either symptoms or anastomotic leakage with a large presacral cavity.

LIMITATIONS:

This study was limited by its small sample size.

CONCLUSIONS:

In the great majority of patients with persistent anastomotic leakage at 6 months after total mesorectal excision, stoma reversal can be safely performed.
Stage-Dependent Frequency of Lymph Node Metastases in Patients With Rectal Carcinoma After Preoperative Chemoradiation: Results from the CAO/ARO/AIO-94 Trial and From a Comparative Prospective Evaluation With Extensive Pathological Workup
Authors: Sprenger Thilo , Rothe Hilka , Conradi Lena-Christin , Beissbarth Tim , Kauffels Anne , Kitz Julia , Homayounfar Kia , Wolff Hendrik , Ströbel Philipp , Ghadimi Michael , Wittekind Christian , Sauer Rolf , Rödel Claus , Liersch Torsten
Published: April 2016

BACKGROUND:

For patients with ycT1/2 rectal carcinomas after neoadjuvant chemoradiotherapy, local excision instead of radical surgery has increasingly been discussed as a way to avoid postoperative morbidity associated with radical surgery.

OBJECTIVE:

The purpose of this study was to determine the incidence of lymph node metastases in total mesorectal excision specimens with ypT0, ypT1/2, and ypT3/4 rectal cancers.

DESIGN:

This is a prospective and retrospective cohort study.

SETTINGS:

This study was conducted in tertiary referral hospitals that are part of the German Rectal Cancer Study Group.

PATIENTS:

A total of 479 patients with stage II and III rectal cancers treated within phase III trials of the German Rectal Cancer Study Group were evaluated. Specimens from 81 patients treated in the Working Group of Surgical Oncology/Working Group of Radiation Oncology/Working Group of Medical Oncology of the Germany Cancer Society (CAO/ARO/AIO-04) trial were prospectively studied with extensive microscopic screening of the entire mesorectum. The frequency and localization of nodal metastases were specified and compared with those of 398 patients having received neoadjuvant chemoradiation within the CAO/ARO/AIO-94 trial.

MAIN OUTCOME MEASURES:

Frequency and localization of mesorectal lymph node metastases in patients with ypT0, ypT1/2, or ypT3/4 cancer were measured.

RESULTS:

A mean number of 28.0 ± 13.7 nodes were detected per specimen within the prospective group. A total of 25% of patients in the ypT1/2 group had nodal metastases compared with 40% in the ypT3/4 group. Patients with node-positive ypT1/2 had a mean number of 2.2 metastases, and 55% of these metastases were located far from the primary lesion in the proximal mesorectum. Within the CAO/ARO/AIO-94 cohort (n = 398), 19% of patients with ypT1/2 (ypT1 = 22%; ypT2 = 18%) had ypN+ status compared with 43% with ypT3/4 cancers (ypT3 = 40%; ypT4 = 73%).

LIMITATIONS:

Low numbers of patients with ypT0 limited the evaluation of nodal metastases in pathologic complete responders.

CONCLUSIONS:

Even in good responders (ypT1/2), >20% of rectal carcinomas still harbored residual lymph node metastases. Local excision for patients with ycT1/2 rectal cancers would, thus, miss metastases in a considerable percentage and might involve the risk of significant undertreatment in a number of patients.
Large Variation in Blood Transfusion Use After Colorectal Resection: A Call to Action
Authors: Aquina Christopher T. , Blumberg Neil , Probst Christian P. , Becerra Adan Z. , Hensley Bradley J. , Noyes Katia , Monson John R. T. , Fleming Fergal J.
Published: April 2016

BACKGROUND:

Perioperative blood transfusions are associated with an increased risk of adverse postoperative outcomes through immunomodulatory effects.

OBJECTIVE:

The purpose of this study was to identify factors associated with variation in blood transfusion use after elective colorectal resection and associated postoperative infectious complications

DESIGN:

This was a retrospective cohort study.

SETTINGS:

The study included elective colorectal resections in New York State from 2001 to 2013.

PATIENTS:

The study cohort consists of 125,160 colorectal resections. Patients who were admitted nonelectively or who were admitted before the date of surgery were excluded.

MAIN OUTCOME MEASURES:

Receipt of a perioperative allogeneic red blood cell transfusion and the secondary end points of postoperative pneumonia, surgical site infection, intra-abdominal abscess, and sepsis were measured.

RESULTS:

The overall rate of perioperative blood transfusion for the study cohort was 13.9%. The unadjusted blood transfusion rates ranged from 2.4% to 58.7% for individual surgeons and 2.9% to 32.8% for individual hospitals. After controlling for patient-, surgeon-, and hospital-level factors in a 3-level mixed-effects multivariable model, significant variation was still present across both surgeons (p < 0.0001) and hospitals (p < 0.0001), with a 16.8-fold difference in adjusted blood transfusion rates across surgeons and a 13.2-fold difference in adjusted blood transfusion rates across hospitals. Receipt of a blood transfusion was also independently associated with pneumonia (OR = 3.23 (95% CI, 2.92–3.57)), surgical site infection (OR = 2.27 (95% CI, 2.14–2.40)), intra-abdominal abscess (OR = 2.72 (95% CI, 2.41–3.07)), and sepsis (OR = 4.51 (95% CI, 4.11–4.94)).

LIMITATIONS:

Limitations include the retrospective design and the possibility of miscoding within administrative data.

CONCLUSIONS:

Large surgeon- and hospital-level variations in perioperative blood transfusion use for patients undergoing colorectal resection are present despite controlling for patient-, surgeon-, and hospital-level factors. In addition, receipt of a blood transfusion was independently associated with an increased risk of postoperative infectious complications. These findings support the creation and implementation of perioperative blood transfusion protocols aimed at limiting unwarranted variation.
Activation of Peroxisome Proliferator-activated Receptor γ Prevents Development of Heart Failure With Preserved Ejection Fraction; Inhibition of Wnt-β-catenin Signaling as a Possible Mechanism
Authors: Kamimura Daisuke , Uchino Kazuaki , Ishigami Tomoaki , Hall Michael E. , Umemura Satoshi
Published: April 2016

Left ventricular (LV) fibrosis plays an important role in the development of heart failure with preserved ejection fraction (HFpEF). We investigated whether chronic peroxisome proliferator-activated receptor gamma agonism with pioglitazone can prevent the development of HFpEF. We also evaluated the role of Wnt-β-catenin signaling in the development of HFpEF, and its relationship to peroxisome proliferator-activated receptor gamma signaling. Dahl salt-sensitive rats placed on an 8% NaCl diet from age 6 weeks were used as HFpEF model. Rats placed on 0.3% NaCl diet served as controls (n = 7). HFpEF model rats were randomized to no treatment (n = 7) or treatment with pioglitazone (2.5 mg/kg per day, n = 7) at age 13 weeks. Pioglitazone administration from age 13 to 21 weeks attenuated the development of LV fibrosis and stiffening (both P < 0.05), and subsequently prevented the development of HFpEF. In the untreated HFpEF model, Wnt1, 2, 10b messenger RNA and β-catenin protein expression levels in the left ventricle increased in the heart failure stage, along with the increase in type I collagen messenger RNA expression levels. Administration of pioglitazone attenuated the activation of Wnt-β-catenin signaling. Our results show that pioglitazone prevented the development of LV fibrosis and HFpEF in a rat model, at least partly due to attenuated Wnt-β-catenin signaling.
N-Methyl-D-Aspartate Receptor Signaling and Function in Cardiovascular Tissues
Authors: McGee Marie A. , Abdel-Rahman Abdel A.
Published: April 2016

Excellent reviews on central N-methyl-d-aspartate receptor (NMDAR) signaling and function in cardiovascular regulating neuronal pools have been reported. However, much less attention has been given to NMDAR function in peripheral tissues, particularly the heart and vasculature, although a very recent review discusses such function in the kidney. In this short review, we discuss the NMDAR expression and complexity of its function in cardiovascular tissues. In conscious (contrary to anesthetized) rats, activation of the peripheral NMDAR triggers cardiovascular oxidative stress through the PI3K-ERK1/2-NO signaling pathway, which ultimately leads to elevation in blood pressure. Evidence also implicates Ca2+release, in the peripheral NMDAR-mediated pressor response. Despite evidence of circulating potent ligands (eg, D-aspartate andl-aspartate,l-homocysteic acid, and quinolinic acid) and also their coagonist (eg, glycine ord-serine), the physiological role of peripheral cardiovascular NMDAR remains elusive. Nonetheless, the cardiovascular relevance of the peripheral NMDAR might become apparent when its signaling is altered by drugs, such as alcohol, which interact with the NMDAR or its downstream signaling mechanisms.
SLC22A1/OCT1 Genotype Affects O-desmethyltramadol Exposure in Newborn Infants
Authors: Matic Maja , de Wildt Saskia N. , Elens Laure , de Hoon Jan N. , Annaert Pieter , Tibboel Dick , van Schaik Ron H. N. , Allegaert Karel
Published: April 2016

Background:

This study determined whether the SLC22A1 [encoding the organic cation transporter 1 (OCT1)] genotype could explain, in addition to the postmenstrual age (referring to gestational plus postnatal age) and CYP2D6 genotype, the tramadol (M) pharmacokinetic variability in early infancy.

Methods:

Fifty infants, median postmenstrual age 39.5 (interquartile range: 36.8–41.3) weeks, received an i.v. M loading dose (2 mg/kg) followed by a continuous infusion (5–8 mg·kg−1·24 h−1). Blood was sampled from 4 to 24 hours after start of the M treatment, which generated 230 observations. M and O-desmethyltramadol (M1) concentrations were measured by high-performance liquid chromatography.

Results:

Linear mixed-model analysis illustrated that the SLC22A1/OCT1 genotype was independently associated with a log-transformed M1/M ratio (P = 0.013), with carriers of <2 SLC22A1/OCT1 functional gene copies having a higher M1/M ratio (2.25; 95% CI, 2.01–2.48) than infants with 2 functional gene copies (1.86; 95% CI, 1.66–2.06). The CYP2D6/SLC22A1 combined genotype was associated with 57.8% higher M1/M ratio in carriers of ≥2 CYP2D6 functional gene copies and <2 SLC22A1/OCT1 functional gene copies compared with infants with <2 active CYP2D6 functional gene copies and SLC22A1/OCT1 normal activity (P < 0.001).

Conclusions:

These findings highlight the additional role of SLC22A1/OCT1 genetics in M1 exposure in neonates. They also suggest that OCT1 is already active early after birth, which may have impact on the disposition of other OCT1 substrates in this population.
Maternal Responses to Aerobic Exercise in Pregnancy
Authors: DAVENPORT MARGIE H. , SKOW RACHEL J. , STEINBACK CRAIG D.
Published: April 2016

Exercise is one of the most physiologically challenging stressors requiring the coordination of metabolic, respiratory, and cardiovascular responses to meet increased energy requirements of the working muscle. During pregnancy, all women without contraindication are encouraged to exercise as part of a healthy lifestyle. Pregnancy itself is associated with profound physiological adaptations to the maternal cardiovascular, respiratory, and metabolic systems, which serve to support the needs of the growing fetus. Therefore the physiological adaptations to exercise during pregnancy are more pronounced and critically important. This review provides an overview of our current understanding of the physiological adaptations to acute prenatal exercise.
SPECTRAL-DOMAIN OPTICAL COHERENCE TOMOGRAPHY EVALUATION OF RETINAL STRUCTURE IN PATIENTS WITH SUSACS SYNDROME
Authors: Agarwal Aniruddha , Soliman Mohamed , Sarwar Salman , Sadiq Mohammad Ali , Do Diana V. , Nguyen Quan Dong , Sepah Yasir Jamal
Published: April 2016

Purpose:

To report spectral-domain optical coherence tomography (SD-OCT) features in patients diagnosed with Susacs syndrome.

Methods:

Clinical report of two cases.

Results:

Spectral-domain optical coherence tomography was performed in two patients diagnosed with Susacs syndrome. Both the patients had normal macular perfusion on fluorescein angiography (FA). However, SD-OCT revealed bilateral, temporal macular atrophy with disorganization and thinning of the retinal layers. The outer plexiform layer showed nodularity and waviness suggestive of ischemic swelling of the bipolar cells.

Conclusion:

Retinal structural changes in Susacs syndrome have not been described earlier. Spectral-domain optical coherence tomography may be more sensitive than fluorescein angiography in detecting microstructural retinal alterations in various layers, especially in apparently perfused retina. These findings may provide an insight into the pathogenesis of Susacs syndrome.
Corneal Higher-Order Aberrations of the Anterior Surface, Posterior Surface, and Total Cornea After SMILE, FS-LASIK, and FLEx Surgeries
Authors: Wu Wenjing , Wang Yan
Published: April 2016

Objectives:

To investigate the corneal higher-order aberrations (HOAs) of the anterior surface, posterior surface, and total cornea after small incision lenticule extraction (SMILE) and compare the results using femtosecond laser-assisted in situ keratomileusis (FS-LASIK) and femtosecond laser lenticule extraction (FLEx).

Methods:

This study included 160 eyes in total; 73 eyes underwent SMILE, 52 eyes underwent FS-LASIK, and 35 eyes underwent FLEx surgery. Corneal HOAs of the anterior surface, posterior surface, and total cornea were evaluated using a Scheimpflug camera over 6-mm diameter preoperatively and 3 months postoperatively.

Results:

The anterior and total corneal HOAs significantly increased after SMILE, FS-LASIK, and FLEx surgeries, especially the spherical aberration and coma, whereas most posterior corneal HOAs remained unchanged. The SMILE procedure induced significantly lower anterior corneal and total corneal spherical aberration and third to eighth HOAs compared with FLEx surgery (P<0.01). FLEx surgery induced higher posterior corneal coma than SMILE (P=0.013) and FS-LASIK (P<0.001) surgeries.

Conclusions:

SMILE, FS-LASIK, and FLEx surgeries mainly induced coma and spherical aberrations in the anterior surface and total cornea. The SMILE procedure induced less spherical aberration of the anterior cornea and total cornea than FLEx surgery. The posterior corneal spherical aberration significantly increased after FS-LASIK surgery. The SMILE procedure seems to have fewer effects on posterior corneal coma compared with the FLEx procedure.
Care System Versus Transmitted Light Wavefront Pattern of Contact Lenses
Authors: Chiericati Stefano , Borghesi Alessandro , Cozza Federica , Ferraro Lorenzo , Acciarri Maurizio , Farris Stefano , Tavazzi Silvia
Published: April 2016

Objectives:

This article compares the optical performance of soft contact lenses (CLs) treated with multipurpose or hydrogen peroxide care systems.

Methods:

The investigated care systems were (1) 3% hydrogen peroxide solution Oxysept (Abbot Medical Optics, Abbott Park, IL) and (2) multipurpose solution Regard (Vita Research, Ariccia, Italy). Three types of silicone hydrogel CLs were studied (comfilcon A, lotrafilcon B, and balafilcon A), unworn and exposed for 30 times to the solutions, which were replaced every 8 hr. The optical performance of the CLs was evaluated through the on-eye transmitted light wavefront patterns by considering new CLs as references. The surface morphology of the CLs was investigated by scanning electron microscopy.

Results:

Statistically significant modifications in the range 0.1 to 0.3 μm of Zernicke coefficients and modifications of the root mean square of the wavefront aberration function were found for CLs treated with multipurpose solution, in agreement with the observed modifications of the surface morphology. Statistically significant changes were also found after exposure to the hydrogen peroxide solution, but the variation of the Zernicke coefficients was found lower than 0.1 μm, thus being negligible in CL optical performances.

Conclusions:

In addition to disinfection ability and ocular surface reactions, CL care systems are different in solution-related CL optical performance. Multipurpose solutions may affect the CL surface morphology with significant modifications of the transmitted light wavefront pattern.
Leak-Free Clear Corneal Incisions in Human Cadaver Tissue: Femtosecond Laser–Created Multiplanar Incisions
Authors: Hill James E. , Binder Perry S. , Huang Ling C.
Published: April 2016

Objectives:

To evaluate femtosecond (FS) laser–assisted leak-free clear corneal incisions (CCI) and paracentesis (P) in human eyes of deceased donors.

Methods:

Multiplanar CCI and P were created using an FS laser on human eyes of deceased donors (whole globe and corneal rims). Laser settings were programmed to multiplanar for CCI and single plane for P. Corneas were imaged by optical coherence tomography (OCT) and evaluated for leak by Seidel testing at various intraocular pressure (IOP) levels, and the wound was manipulated to mimic cataract surgery. Corneal endothelium cell damage and histological architecture were evaluated by microscopy.

Results:

The corneal incision software of the FS laser was used to create homogeneous CCI and P incisions. Morphological changes assessed by OCT and light microscopy/scanning electron microscopy showed consistent true multiplanar incisions with predefined intersecting planes. All Seidel testing was negative, indicating that FS laser–assisted incisions did not leak. Trypan blue stain of the endothelial surface showed limited cell damage from the FS laser incisions.

Conclusions:

The FS laser–created incisions corresponded well with the treatment plans, as evidenced by true multiplanar architecture. Incisions were sharply demarcated and demonstrated limited cell damage. No postprocedure leaking at extreme IOP or postcataract surgery–simulated conditions was noted. The FS laser may potentially reduce postoperative complications, such as infections that may be associated with CCI.
A Novel Surgical Approach for Oculodermal Melanocytosis: Superficial Sclerectomy
Authors: Jung Seungil , Kwon Taejung , Zhang Cheng C. , Chuck Roy S. , Kwon Ji Won
Published: April 2016

Objective:

To report the outcomes of a new surgical method for oculodermal melanocytosis (nevus of Ota)—superficial scleral separation.

Methods:

Twenty-five eyes of 25 patients with scleral pigmentation arising from oculodermal melanocysis. These patients underwent superficial scleral separation between March 2012 and February 2013. Each patient was evaluated with the followings: ocular examinations, the preoperative extent of scleral involvement of nevus of Ota, satisfaction score after surgery, histologic examination, and postoperative complications. Main outcome measures were best-corrected visual acuity (BCVA), induced refractive error, intraocular pressure (IOP), patient satisfaction scores, and anterior segment photographs.

Results:

All patients showed cosmetic improvement without any serious complications. Preoperative and postoperative BCVA, IOP, and refractive outcomes did not change significantly.

Conclusions:

Superficial scleral separation is an effective procedure for cosmetic improvement of oculodermal melanocytosis.
Modified Canaloplasty: A New, Effective, and Safe Option for Glaucoma Patients With a Disrupted Schlemm Canal Wall
Authors: Xin Chen , Chen Xiaoya , Shi Yan , Wang Huaizhou , Wang Ningli
Published: April 2016

Purpose:

We describe a modified canaloplasty technique and report the short-term efficacy for primary open-angle glaucoma (POAG) patients with disruption of Schlemm canal (SC) wall resulting from prior glaucoma surgery.

Patients and Methods:

This was a single-surgeon prospective cohort study. POAG patients scheduled for canaloplasty were included and divided into 2 groups: group1 included POAG patients without a history of glaucoma surgery and group 2 included POAG patients with failed glaucoma surgery and disrupted SC. The status of SC was determined by gonioscopy and ultrasound biomicroscopy. Standard canaloplasty procedures were performed in group 1. A modified canaloplasty technique was used in group 2. Primary outcome measures included the intraocular pressure and glaucoma medication use at various follow-up points.

Results:

Seventeen patients were enrolled in group 1 and 9 patients were enrolled in group 2. At the 12-month follow-up, there was no significant difference between groups 1 and 2 (17.8±2.7 vs. 16.7±2.4 mm Hg, respectively; P=0.362) and in the mean number of medications (0.9±1.2 vs. 0.3±0.5, respectively; P=0.061). In both groups, at all follow-up points, the intraocular pressure and the mean glaucoma medication usage had decreased significantly compared with measurements at baseline (P<0.001). The rate for successful circumferential catheterization was not significant between the 2 groups (88.2% vs. 77.8%, P=0.063).

Conclusion:

Modified canaloplasty is a feasible, safe, and potentially effective option for patients with POAG and regions of SC disruption resulting from previous glaucoma-filtering surgery.
IOP Elevation After Cataract Surgery: Results for Residents and Senior Staff at Henry Ford Health System
Authors: Elfersy Adrian J. , Prinzi Robert A. , Peracha Zuhair H. , Kim Daniel D. , Crandall David A. , Darnley-Fisch Deborah A. , Imami Nauman R.
Published: April 2016

Purpose:

To determine the incidence of intraocular pressure (IOP) elevation on postoperative day 1 (POD1) after cataract surgery performed by resident surgeons compared with attending surgeons and to examine the influence of associated variables on the incidence of postoperative IOP elevation.

Patients and Methods:

Retrospective review of 2472 consecutive 2.2 to 2.8 mm temporal clear corneal cataract extractions by phacoemulsification performed by either residents or attending surgeons at Henry Ford Health System. Fellow eyes were excluded, resulting in 1847 eyes. IOP measurements of >40, >30, and >23 mm Hg were noted along with incremental IOP elevations of ≥10 and 20 mm Hg over preoperative/baseline IOP. Associated variables included: age, sex, diabetes mellitus, hypertension, glaucoma, glaucoma suspect, uveitis, prior ocular trauma, and vitreous loss at surgery.

Results:

Resident-performed cataract surgery was associated with statistically significant higher rates of IOP elevation in all categories and in all clinical situations known to be associated with postoperative IOP spike, that is, vitreous loss at surgery, prior ocular trauma, and preexisting glaucoma.

Conclusions:

The incidence of postoperative day 1 IOP elevation after phacoemulsification performed by resident surgeons was 2 to 5 times that of experienced cataract surgeons. Variables including vitreous loss at surgery, prior ocular trauma, preexisting glaucoma, glaucoma suspect status, and male sex were significant contributors. Consideration for prophylactic IOP lowering is advised in high-risk patients.
Intraoperative Management of Hypercapnia with an Extracorporeal Carbon Dioxide Removal Device during Giant Bullectomy
Authors: Dell'Amore Andrea , D'Andrea Rocco , Caroli Guido , Mazzoli Carlo Alberto , Rocca Alberto , Stella Franco , Bini Alessandro , Melotti Rita
Published: April 2016

Extracorporeal CO2-removal devices have been introduced in clinical practice to provide protective and ultraprotective ventilation strategies in different settings to avoid retention of carbon dioxide. The need to facilitate lung-protective ventilation is required not only for the treatment of acute respiratory distress syndrome but also in thoracic surgery during complex operations, especially in respiratory compromised patients. This report describes a case of giant bullectomy for vanishing lung syndrome in which intraoperative hypercapnia secondary to protective ventilation was managed with a CO2-removal device (Decap-Hemodec s.r.l., Salerno, Italy). To the best of our knowledge, this is the first report in the literature of the intraoperative use of the Decap system for giant bullectomy.
Childhood Optic Nerve Glioma: Vision Loss Due to Biopsy
Authors: Revere Karen E. , Katowitz William R. , Katowitz James A. , Rorke-Adams Lucy , Fisher Michael J. , Liu Grant T.
Published: April 2016

Two children without neurofibromatosis type 1 presented with unilateral decreased vision and MRI revealing optic nerve tumors. In the first case, chemotherapy was initiated empirically for presumed optic pathway glioma, but the lesion increased in size with associated clinical worsening, raising concern for a possible alternate diagnosis. Biopsy of the involved optic nerve resulted in worsening of vision due to a branch retinal artery occlusion and showed a grade I pilocytic astrocytoma. In the second case, sudden symptom onset and rapid tumor growth prompted an optic nerve biopsy, resulting in vision loss due to a central retinal artery occlusion and revealing grade I pilocytic astrocytoma. In both cases, tissue diagnosis did not alter the course of management. Instead, biopsy was associated with additional vision loss, highlighting the risk of biopsy in children with isolated optic nerve tumors and imaging that is most consistent with an optic pathway glioma.
Reversible Blindness Following Orbital Fracture Repair
Authors: Joos Zachary P. , Patel Bhupendra C. K.
Published: April 2016

The authors report a case of a 72-year-old woman with unilateral, complete, reversible blindness (no light perception) immediately after uncomplicated repair of an orbital floor fracture. In this case, vision loss was reversed with prompt surgical intervention with removal of the orbital floor implant. The authors review the etiology of vision loss after orbital fracture repair and hypothesize as to the cause of blindness in this case. Given the frequency with which orbital fracture repair is performed by a variety of surgical subspecialists, it is imperative for surgeons to be familiar with the ophthalmic complications and be aware of the multiple causes of postoperative vision loss. The authors propose that immediate postoperative assessment of visual function be performed on all patients undergoing orbital fracture repair.
Topical Plasminogen as Adjunctive Treatment in Recurrent Ligneous Conjunctivitis
Authors: Ang Michael J. , Papageorgiou Konstantinos I. , Chang Shu-Hong , Kohn Jocelyn , Chokron Garneau Helen , Goldberg Robert A.
Published: April 2016

Ligneous conjunctivitis is a rare, autosomal recessive, membranous conjunctivitis characterized by a deficiency in type 1 plasminogen. The absence of normal plasmin activity results in the formation of fibrin-rich, membranous material that typically manifests on the palpebral conjunctiva. Surgical treatment often causes irritation of the conjunctiva and accelerated recurrence of pseudomembranes. In this interventional case report, the authors document the results of treatment with topical plasminogen following conjunctival pseudomembrane excision in a 32-year-old woman. The patient underwent pseudomembrane excision in the OS followed immediately by hourly topical application of plasminogen eye drops. The plasminogen was prepared from pooled human plasma purchased under Food and Drug Administration approval from DiaPharma. Follow-up evaluation at 1 week, 1 month, and 5 months showed no evidence of recurrent pseudomembranous change. Adjunctive topical plasminogen application appears to be an effective and safe method of controlling pseudomembrane recurrence in patients with ligneous conjunctivitis.
Glomuvenous Malformation: A Rare Periorbital Lesion of the Thermoregulatory Apparatus
Authors: Whipple Katherine M. , Godfrey Kyle J. , Solomon James P. , Lin Jonathan H. , Korn Bobby S. , Kikkawa Don O.
Published: April 2016

Glomuvenous malformations (GVMs), previously referred to as glomus tumors or glomangiomas, are benign, mesenchymal venous malformations arising from glomus bodies. Glomus bodies are modified smooth muscle neuromyoarterial structures involved in temperature regulation via blood shunting. These classically occur in the digits but can occur in other locations. The authors present a case of a periorbital GVM presented following blunt trauma to the area.