bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased Postoperative Morbidity Associated With Prolonged Laparoscopic Colorectal Resections Is Not Increased by Resident Involvement
Authors: Kulaylat Audrey S. , Hollenbeak Christopher S. , Stewart David B. 
Published: March 2018

BACKGROUND:
Although longer operative times are associated with increased postoperative morbidity, the influence of surgical residents on this association is unclear.

OBJECTIVE:
The purpose of this study was to evaluate whether morbidity associated with operative times in laparoscopic colorectal surgery is increased by resident training.

DESIGN:
This was a retrospective cohort study.

SETTINGS:
The study was conducted using a national database.

PATIENTS:
Laparoscopic ileocolectomies, partial colectomies, and low anterior resections were identified in the National Surgical Quality Improvement Project (2005–2012). This cohort was stratified by the presence of resident involvement (postgraduate clinical year ≤5) and then divided into tertiles of operative time (low, medium, and high), allowing comparisons of cases by duration with resident involvement with cases of similar length without resident involvement.

MAIN OUTCOME MEASURES:
Postoperative morbidity (infectious and noninfectious), length of hospital stay, and unplanned reoperations were the primary study outcomes.

RESULTS:
A total of 20,785 procedures were identified. In aggregate, prolonged operative time was associated with both infectious (OR = 1.49, p < 0.001 with residents; OR = 1.38, p < 0.001 without residents) and noninfectious complications (OR = 1.51, p < 0.001 with residents; OR = 1.48, p < 0.001 without residents) when compared with short cases without residents. Longer hospital stay was observed both within the highest (additional 1.2 days (p < 0.001) with residents; 1.1 days (p < 0.001) without residents) and middle (additional 0.4 days (p < 0.001) with residents; 0.4 days (p = 0.001) without residents) tertiles of operative time. Within the highest tertile of operative length, there was no statistically significant difference in complication rates between cases with and without resident participation.

LIMITATIONS:
The study was limited by its retrospective design and inability to define the complexity of case and extent of resident involvement.

CONCLUSIONS:
Although longer operative times confer increased postoperative morbidity, there was no significant difference in complication rates within the highest tertile between cases with and without resident participation. Resident involvement does not appear to add to the risk of morbidity associated with longer and more complicated surgeries. See Video Abstract at http://links.lww.com/DCR/A440.
Recurrence of Rectal Prolapse After Surgical Repair in Women With Pelvic Organ Prolapse
Authors: Catanzarite Tatiana , Klaristenfeld Daniel D. , Tomassi Marco J. , Zazueta-Damian Gisselle , Alperin Marianna 
Published: March 2018

BACKGROUND:
Pelvic organ prolapse is prevalent among women with rectal prolapse.

OBJECTIVE:
This study aimed to determine whether clinically significant pelvic organ prolapse impacts rectal prolapse recurrence after surgical repair.

DESIGN:
A retrospective cohort.

SETTING:
This study was performed at a single managed-care institution.

PATIENTS:
Consecutive women undergoing rectal prolapse repair between 2008 and 2016 were included.

INTERVENTIONS:
There were no interventions.

MAIN OUTCOME MEASURES:
Full-thickness rectal prolapse recurrence was compared between 4 groups: abdominal repair without pelvic organ prolapse (AR−POP); abdominal repair with pelvic organ prolapse (AR+POP); perineal repair without pelvic organ prolapse PR−POP; and perineal repair with pelvic organ prolapse (PR+POP). Recurrence-free period and hazard of recurrence were compared using Kaplan-Meier and Cox proportional hazards methods. To identify potential confounding risk factors for rectal prolapse recurrence, the characteristics of subjects with/without recurrence were compared with univariable and multivariable analyses.

RESULTS:
Overall, pelvic organ prolapse was present in 33% of 112 women and was more prevalent among subjects with rectal prolapse recurrence (52.4% vs 28.6%, p = 0.04). Median follow-up was 42.5 months; rectal prolapse recurrence occurred in 18.8% at a median of 9 months. The rate of recurrence and the recurrence-free period differed significantly between groups: AR−POP 3.8%, 95.7 months; AR+POP 13.0%, 86.9 months; PR−POP 34.8%, 42.1 months; PR+POP 57.1%, 23.7 months (p < 0.001). Compared with AR−POP the HR (95% CI) of rectal prolapse recurrence was 3.1 (0.5–18.5) for AR+POP; 14.7 (3.0–72.9) for PR−POP and 31.1 (6.2–154.5) for PR+POP. Compared with AR+POP, PR+POP had a shorter recurrence-free period (p < 0.001) and a higher hazard of recurrence (HR, 10.2; 95% CI, 2.1–49.3).

LIMITATIONS:
The retrospective design was a limitation of this study.

CONCLUSIONS:
Pelvic organ prolapse was associated with a higher rectal prolapse recurrence rate and earlier recurrence in women undergoing perineal, but not abdominal, repairs. Multidisciplinary evaluation can facilitate individualized management of women with rectal prolapse. Abdominal repair should be considered in women with concomitant rectal and pelvic organ prolapse. See Video Abstract at http://links.lww.com/DCR/A513.
Closing Perianal Fistulas Using a Laser: Long-Term Results in 103 Patients
Authors: Terzi Mustafa Cem , Agalar Cihan , Habip Sari , Canda Aras Emre , Arslan Naciye Cigdem , Obuz Funda 
Published: March 2018

BACKGROUND:
Primary closure of the fistula tract using energy emitted by a radial fiber connected to a diode laser is a novel procedure for treating perianal fistulas.

OBJECTIVE:
The aim of this study was to determine the long-term effectiveness of this new technique.

DESIGN:
The surgical objective was to seal the fistula tract using laser energy.

SETTINGS:
The study was conducted at a single day-case surgery center.

PATIENTS:
Between April 2012 and June 2016, 103 consecutive patients with primary or recurrent perianal fistula underwent a laser closure procedure using a 12-watt laser emitting at a wavelength of 1470 nm.

MAIN OUTCOME MEASURES:
Patients were classified according to the Park classification, and healing was evaluated based on the perianal fistula disease severity score.

RESULTS:
Among the 103 patients treated using the laser closure procedure, 82 (80%) were men and 21 (20%) were women. The median age of the patients was 43 years (range, 18–78 y). Fifty-three patients (52%) had previous perianal fistula repair surgery. Based on the Park classification, 56 patients (54%) had intersphincteric fistula, 29 (28%) had transsphincteric fistula, 11 (11%) had suprasphincteric or extrasphincteric fistula, and 7 (7%) had superficial perianal fistula. Based on the perianal disease severity score, 41 patients (40%) obtained overall complete healing, 38 (37%) had persistent symptomatic drainage, 20 (19%) had slight drainage with minimal symptoms, and 4 (4%) had painful symptomatic drainage.

LIMITATIONS:
This was a retrospective analysis of noncomparative data with a lack of formal prospective continence assessment.

CONCLUSIONS:
Closure of perianal fistulas using a laser should be considered as a treatment option but with modest expectations. Although our complete healing rate was not as high as in earlier studies, this technique is a reasonable option with nearly no risk of sphincter damage when treating perianal fistulas. See Video Abstract at http://links.lww.com/DCR/A545.
Relationship of Anticoagulant Therapy With Cognitive Impairment Among Patients With Atrial Fibrillation: A Meta‐Analysis and Systematic Review
Authors: Cheng Wenke , Liu Weijun , Li Bin , Li Dongfang 
Published: March 2018

Background:
At present, it is considered that atrial fibrillation (AF) is a risk factor for cognitive impairment and dementia. It is independent of stroke, but the relationship between anticoagulant drugs and cognitive function in patients with AF is unknown.

Objective:
The purpose of this study was to complete a meta-analysis of studies and investigate the association between anticoagulant therapy and cognitive impairment in patients with AF.

Methods and Results:
Two investigators systematically searched the Cochrane Library, PubMed, EMBASE databases, and Web of Science for all studies that present associations. Hazard ratios (HRs) were extracted and pooled. Finally, the 8 studies included 471,057 participants; time in therapeutic range (TTR) <25% versus TTR >75%; (HR 3.02, 95% CI 1.12–8.91; P = 0.03); TTR 25%–50% versus TTR >75% (HR 2.44, 95% CI 0.95–6.22; P = 0.06); TTR 50%–75% versus TTR >75% (HR 1.75, 95% CI 0.90–3.99; P = 0.1); oral anticoagulants (OAC) versus No OAC (HR 0.71, 95% CI 69–0.74; P < 0.00001); and new oral anticoagulants versus warfarin (HR 0.51, 95% CI 0.37–0.71; P < 0.00001).

Conclusions:
OACs significantly reduce the occurrence of cognitive impairment in patients with AF. Compared with warfarin, new oral anticoagulants have an efficiently protective effect on cognition. In the range of INR 2–3, with the increase of TTR, the incidence of cognitive impairment is lower.
Quantification of Idelalisib in Human Plasma by Ultra-Performance Liquid Chromatography Coupled to Mass Spectrometry in Negative Ionization Mode
Authors: Huynh Huu H. , Roessle Clara , Sauvageon Hélène , Plé Alain , Madelaine Isabelle , Thieblemont Catherine , Mourah Samia , Goldwirt Lauriane 
Published: March 2018

Background:
Idelalisib is the first orally active selective phosphatidylinositol 3-kinase delta inhibitor approved by Food and Drug Administration and European Medicines Agency in 2014 for the treatment of several types of blood cancer. Idelalisib is widely used as a monotherapy or in combination with rituximab, bendamustine, or ofatumumab with a significant efficacy. However, idelalisib has shown increased risk of infection and a higher frequency of serious adverse events. It may be useful to determine idelalisib concentration in human plasma to adjust dose and to manage adverse effects in clinical practice.

Methods:
After a single-step protein precipitation of plasma samples, the chromatographic separation was performed using an ultra-high performance liquid chromatography system coupled with mass tandem spectrometry in a negative ionization mode using isotope-labeled internal standard. This method was validated by studies of its linearity, accuracy, imprecision, limit of quantification, recovery, matrix effect, selectivity, and stability.

Results:
The quantification method was linear from 10 to 2500 ng/mL with a 5 ng/mL lower limit of quantification that encompasses the clinical range of drug concentration. The intraday and interday imprecisions were below 8.1% and 11.4%, respectively. The recoveries and matrix effect of idelalisib were 85.6% ± 1.2% and 95.7% ± 3.0%, respectively, which are consistent, precise, and reproducible (coefficient of variation % < 15%). Peak plasma concentration and trough plasma concentration ranges of idelalisib reached 1591–1937 ng/mL and 256.3–303.3 ng/mL, respectively, in 3 follicular lymphoma patients treated with idelalisib 150 mg twice a day.

Conclusions:
A robust and sensitive liquid chromatography–tandem mass spectrometry method was developed and validated to quantify idelalisib concentration in human plasma. This method was effectively applied to 3 follicular lymphoma patients.
Potential of Oral Fluid as a Clinical Specimen for Compliance Monitoring of Psychopharmacotherapy
Authors: Neumann Jasna , Beck Olof , Dahmen Norbert , Böttcher Michael 
Published: March 2018

Background:
Oral fluid (OF) is being developed as a specimen for the determination of drug intake as an alternative to serum and plasma. It is generally considered as an attractive specimen due to the noninvasive nature of the sampling procedure and the relation to the free fraction of drug in the blood. These features are of particular value in drug treatment of psychiatric disorders. To establish OF for the purpose of monitoring drug therapy, the relationship between concentrations in OF and serum/plasma must be documented. This study explored one promising sampling device and comprised the following 10 drugs: aripiprazole, citalopram, duloxetine, escitalopram, mirtazapine, pipamperone, pregabalin, promethazine, quetiapine, and venlafaxine.

Methods:
For this purpose, 100 paired serum and OF samples were collected from patients undergoing pharmacotherapy and analyzed using a liquid chromatography–tandem mass spectrometry method. A commercial method from Chromsystems for the determination of these drugs in plasma was used and was adapted for OF and ultrafiltrated (Centrifree device) serum.

Results:
The ratio of each individual pair of samples was used to calculate a mean and SD value between OF and serum free and total concentrations. The OF concentration ratios to serum total fraction differed markedly between substances and differed from 10-fold lower to 8-fold higher. The ratios to serum free fractions were always higher. The relation between the OF and serum concentrations was also evaluated by regression analysis and determination of slopes and correlation coefficients. For all measured relations, there was a statistically significant relation between the OF and serum concentrations. The degree of drug protein binding was in agreement with literature. The aripiprazole, duloxetine, pipamperone, pregabalin, and promethazine concentrations in ultrafiltrated serum were not possible to measure because of low concentrations and nonspecific binding.

Conclusions:
Despite a strong statistical correlation between OF and serum concentrations observed for most of the studied substances, it is still evident that OF concentrations cannot simply substitute serum/plasma as therapeutic drug monitoring specimen, but rather be considered as a unique specimen. We believe that OF is a promising matrix especially for compliance testing in psychiatry settings. The Greiner Bio-One device used in this study provides a sampling procedure that offers advantages over the available alternatives.
Explaining Interpatient Variability in Adalimumab Pharmacokinetics in Patients With Crohn's Disease
Authors: Berends Sophie E. , Strik Anne S. , Van Selm Juliet C. , Löwenberg Mark , Ponsioen Cyriel Y. , D'Haens Geert R. , Mathôt Ron A. 
Published: March 2018

Background:
A significant proportion of patients with Crohn's disease (CD) require dose escalation or fail adalimumab (ADL) therapy over time. ADL, a monoclonal antibody directed against tumor necrosis factor, is approved for treatment of CD. Understanding pharmacokinetics (PK) of ADL is essential to optimize individual dosing in daily practice. The aim of this study was to evaluate PK of ADL in patients with CD and to identify factors that influence PK of ADL.

Methods:
In a retrospective cohort study, the authors reviewed the charts of 96 patients with CD receiving ADL induction and maintenance treatment. This patient cohort was used for external validation of population pharmacokinetic models of ADL available from literature. In addition, a novel population PK model was developed using nonlinear mixed-effects modeling.

Results:
None of the literature models properly described the PK of ADL in our cohort. Therefore, a novel population pharmacokinetic model was developed. Clearance of ADL increased 4-fold in the presence of anti-ADL antibodies. Patients who received ADL every week had a 40% higher clearance compared with patients receiving ADL every other week.

Conclusions:
Clearance of ADL increased in the presence of anti-ADL antibodies and was associated with weekly ADL administrations. In clinical practice, the decision to intensify ADL treatment to weekly administrations is primarily based on disease activity. Increased disease activity may be the result of lower drug concentrations due to higher clearance. However, increased disease activity may also increase clearance due to increased target engagement. The causal relationship between these factors remains to be elucidated.
Acute Kidney Injury Biomarkers Predict an Increase in Serum Milrinone Concentration Earlier Than Serum Creatinine–Defined Acute Kidney Injury in Infants After Cardiac Surgery
Authors: Gist Katja M. , Cooper David S. , Wrona Julia , Faubel Sarah , Altmann Christopher , Gao Zhiqian , Marino Bradley S. , Alten Jeffrey , Hock Kristal M. , Mizuno Tomoyuki , Vinks Alexander A. , Joy Melanie S. , Wempe Michael F. , Bennett Michael R. , Goldstein Stuart L. 
Published: March 2018

Background:
Milrinone, an inotropic agent used ubiquitously in children after cardiac surgery, accumulates in acute kidney injury (AKI). We assessed if urinary AKI biomarkers are predictive of an increase in milrinone concentrations in infants after cardiac surgery.

Methods:
Multicenter prospective pilot study of infants undergoing cardiac surgery. Urinary AKI biomarkers were measured in the urine at specific time intervals after cardiopulmonary bypass initiation. AKI was defined using the Kidney Disease: Improving Global Outcomes serum creatinine criteria. Serum milrinone concentrations were measured at specific intervals after drug initiation, dose changes, and termination. Excessive milrinone activity was defined as a 20% increase in serum concentration between 6 and 36 hours after initiation. The temporal relationship between urinary AKI biomarker concentrations and a 20% increase in milrinone concentration was assessed.

Results:
AKI occurred in 31 (33%) of infants. Milrinone clearance was lower in patients with AKI (4.2 versus 5.6 L/h/70 kg; P = 0.02). Excessive milrinone activity was associated with development of serum creatinine–defined AKI [odds ratio (OR) 3.0; 95% confidence interval (CI), 1.21–7.39; P = 0.02]. Both tissue inhibitor metalloproteinase type 2 and insulin-like growth factor–binding protein type 7 (TIMP-2*IGFBP-7) ≥0.78 at 12 hours (OR 2.72; 95% CI, 1.01–7.38; P = 0.04) and kidney injury molecule 1 (KIM-1) ≥529.57 at 24 hours (OR 2.76; 95% CI, 1.06–7.17; P = 0.04) predicted excessive milrinone activity before a diagnosis of AKI.

Conclusions:
In this pilot study, urine TIMP-2*IGFBP-7 and KIM-1 were predictive of AKI and excessive milrinone activity. Future studies that include a pharmacodynamics assessment of patient hemodynamics, excessive milrinone activity, and AKI biomarker concentrations may be warranted to integrate this concept into clinical practice.
Pyoderma Gangrenosum Secondary to Severe Congenital Neutropenia
Authors: Wakabayashi Nao , Tosa Mamiko , Anzai Shinichi , Ogawa Rei 
Published: March 2018

Summary:
We encountered a case of a man who was diagnosed with severe congenital neutropenia as a child and presented at the age of 45 years with pyoderma gangrenosum (PG) of the lower leg. PG associates with an underlying systemic disease, most commonly inflammatory bowel, rheumatic, or hematological disease or malignancy. However, in many cases, the underlying disease was not known. Surgery can trigger PG. The histopathological features of PG were nonspecific, and diagnosis requires excluding other conditions that have a similar appearance. Our analyses showed that the PG in our case was secondary to severe congenital neutropenia, which had promoted an infection of keratinous cysts. The patient bore a mutation in the ELANE gene encoding neutrophil elastase. Only 1 other case of neutropenia-associated PG has been reported previously: the association was only suspected. The present complex case was effectively treated by systemic treatment of the neutropenia with granulocyte colony–stimulating factor and regional surgical treatment. Histology of the excised tissue revealed keratinous cysts that were diffusely distributed with inflammatory granulation tissue. We believe that the rupture of the walls of the keratinous cysts may have caused the PG. At the time of writing (3 years since the initial presentation), the PG has not recurred. This case shows the importance of performing detailed examinations, including blood tests, to determine the disease underlying PG. This was because if the underlying disease was identified, its treatment was likely to promote healing of the wound after local surgery and prevent recurrence.
A New Approach for the Calculation of Total Corneal Astigmatism Considering the Magnitude and Orientation of Posterior Corneal Astigmatism and Thickness
Authors: Piñero David P. , Caballero María T. , Nicolás-Albujer Juan M. , de Fez Dolores , Camps Vicent J. 
Published: March 2018

Purpose:
To evaluate a new method of calculation of total corneal astigmatism based on Gaussian optics and the power design of a spherocylindrical lens (C) in the healthy eye and to compare it with keratometric (K) and power vector (PV) methods.

Methods:
A total of 92 healthy eyes of 92 patients (age, 17–65 years) were enrolled. Corneal astigmatism was calculated in all cases using K, PV, and our new approach C that considers the contribution of corneal thickness. An evaluation of the interchangeability of our new approach with the other 2 methods was performed using Bland–Altman analysis.

Results:
Statistically significant differences between methods were found in the magnitude of astigmatism (P < 0.001), with the highest values provided by K. These differences in the magnitude of astigmatism were clinically relevant when K and C were compared [limits of agreement (LoA), −0.40 to 0.62 D), but not for the comparison between PV and C (LoA, −0.03 to 0.01 D). Differences in the axis of astigmatism between methods did not reach statistical significance (P = 0.408). However, they were clinically relevant when comparing K and C (LoA, −5.48 to 15.68 degrees) but not for the comparison between PV and C (LoA, −1.68 to 1.42 degrees).

Conclusions:
The use of our new approach for the calculation of total corneal astigmatism provides astigmatic results comparable to the PV method, which suggests that the effect of pachymetry on total corneal astigmatism is minimal in healthy eyes.
A Randomized, Double-blind, Active-controlled Clinical Trial of a Cell Culture-derived Inactivated Trivalent Influenza Vaccine (NBP607) in Healthy Children 6 Months Through 18 Years of Age
Authors: Oh Chi Eun , Choi Ui-Yoon , Eun Byung Wook , Lee Taek Jin , Kim Ki Hwan , Kim Dong Ho , Kim Nam Hee , Jo Dae Sun , Shin Sun Hee , Kim Kyung-Ho , Kim Hun , Kim Yun-Kyung 
Published: March 2018

Background:
Although a number of cell culture–derived influenza vaccines have been approved for use in adults, there have been few clinical trials of cell culture–derived seasonal influenza vaccines for young children.

Methods:
We conducted a randomized, double-blind phase III clinical trial to evaluate the safety and immunogenicity of a cell culture–derived subunit trivalent inactivated influenza vaccine (NBP607, SK Chemicals Co., Ltd., Seongnam, Korea) in healthy children 6 months of age through 18 years. Subjects were randomized to receive either a study vaccine or an egg-based control vaccine. Antibody levels were measured by the hemagglutination inhibition assay, using cell-derived antigens. Solicited adverse events were assessed for 7 days after each injection. Serious adverse events were collected for 6 months after vaccination.

Results:
A total of 374 participants completed the study. No deaths, vaccine-related serious adverse events or withdrawals resulting from adverse events were reported. Rates of solicited and unsolicited adverse events were similar in 2 groups. Overall, NBP607 met the immunogenicity criteria of the Committee for Proprietary Medicinal Products for the 3 influenza strains. Between the NBP607 group and the control group, immunogenicity endpoints were comparable. Participants younger than 3 years of age had lower immunologic responses against the influenza B virus in both the NBP607 group and the control group.

Conclusions:
The immunogenicity and safety were comparable between the NBP607 group and the control group. NBP607 is well tolerated and immunogenic in children 6 months of age through 18 years.