bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Comparison of SHILLA GROWTH GUIDANCE SYSTEM and Growing Rods in the Treatment of Spinal Deformity in Children Less Than 10 Years of Age
Authors: Luhmann Scott J. , McCarthy Richard E. 
Published: April 2016

Background:
The purpose of this study was to compare the outcomes of the SHILLA GROWTH GUIDANCE SYSTEM and “intermittent distraction growing rod” (IDGR) in the treatment of children (less than 10 y of age) with progressive spinal deformity. This was a multicenter retrospective study of the SHILLA used as an alternative treatment to IDGR to support an HDE submission for Food and Drug Administration approval.

Methods:
Inclusion criteria were progressive scoliosis in a patient less than 10 years of age at index procedure. The study population consisted of 19 SHILLA and 6 IDGR patients whose mean age was 6.1 and 5.8 years, respectively. Group demographics were similar between the 2 groups.

Results:
The initial major curve magnitude was 70.3 degrees for SHILLA and 68.3 degrees for IDGR, which decreased postoperatively to 22.4 degrees (68.1% improvement) and 32.2 degrees (52.9% improvement). During the first 4 years the correction for SHILLA varied from 40.5% to 53.4% and for IDGR from 40.9% to 56.9%. At last follow-up, T1-S1 length was 32.9 cm for SHILLA (4.2 increase from preoperation) and 34.0 cm (5.0 cm increase from preoperation) for IDGR. Average growth per month from T1-S1: SHILLA 0.14 cm, IDGR 0.11 cm. Sagittal T2-T12 preoperatively was 36.3 degrees for SHILLA and 30.0 degrees for IDGR. There were 29 reoperations in 12 of the 19 SHILLA patients (63.2%) and 40 reoperations in all 6 of the IDGR patients (100%) related to the index procedure.

Conclusions:
The SHILLA GROWTH GUIDANCE SYSTEM compares favorably with traditional IDGR constructs in terms of correction of the major curve, spinal length and growth, and maintenance of sagittal alignment. The >4-fold decrease in additional surgeries makes the SHILLA an attractive alternative to minimize comorbidities associated with additional surgeries.

Levels of Evidence:
Level III.
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.
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

Abstract:
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.