bluuebunny/crossref_metadata_2025 huggingface dataset:
Prior staphylococcal bacteremia and risk of surgical site infection after total joint arthroplasty: a nested case-control study
Authors: Everhart Joshua S. , Mayerson Joel L. , Glassman Andrew H. , Barlow Jonathan D. , Bishop Julie Y. , Scharschmidt Thomas J.
Published: November 2017

Background:

Staphylococcus species can become dormant, causing recurrent infection after long latent periods. We sought to determine surgical site infection (SSI) risk after knee, hip, or shoulder arthroplasty with a history of staphylococcal bacteremia.

Methods:

Data on 7604 patients who underwent primary or revision knee, hip, or shoulder arthroplasty were reviewed. Twenty-four cases of prior documented staphylococcal bacteremia were identified. These cases were matched 1:4 to controls with similar procedures, surgical indications, and medical comorbidities. Conditional logistic regression was used to determine the risk of SSI due to prior bacteremia relative to medically similar controls.

Results:

Staphylococcal isolates at the time of most recent bacteremia were methicillin-sensitive S. aureus (MSSA)( 9/24), methicillin-resistant S. aureus (MRSA)(8/24), and methicillin-resistant S. epidermidis (MRSE)(7/24). Prior patients with bacteremia who developed subsequent SSI (46%, 11/24 patients) all presented within 6 mo (mean 32.0 days IQR 10-142) with deep infection and positive perarticular tissue or synovial aspirate cultures. The conditional odds ratio (cOR) for SSI among prior bacteremia patients was greater than 7-fold that of controls (cOR 7.28 CI 2.21, 24.1; P<0.001). Among prior native or periprosthetic joint infection patients, prior bacteremia did not significantly increase recurrent SSI risk after two-stage arthroplasty (cOR 1.52 CI 0.29, 7.94 P=0.62). Among patients without prior joint infections, bacteremia significantly elevated future SSI risk (cOR 28.0 CI 3.44, 227, P=0.002).

Conclusions:

A history of staphylococcal bacteremia poses a significantly elevated risk of deep infection after hip, knee, or shoulder arthroplasty in patients without a prior native or periprosthetic joint infection.
Prolonged Infusion Piperacillin-Tazobactam Decreases Mortality and Improves Outcomes in Severely Ill Patients: Results of a Systematic Review and Meta-Analysis*
Authors: Rhodes Nathaniel J. , Liu Jiajun , O’Donnell J. Nicholas , Dulhunty Joel M. , Abdul-Aziz Mohd H. , Berko Patsy Y. , Nadler Barbara , Lipman Jeffery , Roberts Jason A.
Published: November 2017

Objective:

Piperacillin-tazobactam is a commonly used antibiotic in critically ill patients; however, controversy exists as to whether mortality in serious infections can be decreased through administration by prolonged infusion compared with intermittent infusion. The purpose of this systematic review and meta-analysis was to describe the impact of prolonged infusion piperacillin-tazobactam schemes on clinical endpoints in severely ill patients.

Design:

We conducted a systematic literature review and meta-analysis searching MEDLINE, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Library from inception to April 1, 2017, for studies.

Interventions:

Mortality rates were compared between severely ill patients receiving piperacillin-tazobactam via prolonged infusion or intermittent infusion. Included studies must have reported severity of illness scores, which were transformed into average study-level mortality probabilities.

Measurements and Main Results:

Two investigators independently screened titles, abstracts, and full texts of studies meeting inclusion criteria for this systematic review and meta-analysis. Variables included author name, publication year, study design, demographics, total daily dose(s), average estimated creatinine clearance, type of prolonged infusion, prevalence of combination therapy, severity of illness scores, infectious sources, all-cause mortality, clinical cure, microbiological cure, and hospital and ICU length of stay. The review identified 18 studies including 3,401 patients who received piperacillin-tazobactam, 56.7% via prolonged infusion. Across all studies, the majority of patients had an identified primary infectious source. Receipt of prolonged infusion was associated with a 1.46-fold lower odds of mortality (95% CI, 1.20–1.77) in the pooled analysis. Patients receiving prolonged infusion had a 1.77-fold higher odds of clinical cure (95% CI, 1.24–2.54) and a 1.22-fold higher odds of microbiological cure (95% CI, 0.84–1.77). Subanalyses were conducted according to high (≥ 20%) and low (< 20%) average study-level mortality probabilities. In studies reporting higher mortality probabilities, effect sizes were variable but similar to the pooled results.

Conclusions:

Receipt of prolonged infusion of piperacillin-tazobactam was associated with reduced mortality and improved clinical cure rates across diverse cohorts of severely ill patients.
Is the Distance Worth It? Patients With Rectal Cancer Traveling to High-Volume Centers Experience Improved Outcomes
Authors: Xu Zhaomin , Becerra Adan Z. , Justiniano Carla F. , Boodry Courtney I. , Aquina Christopher T. , Swanger Alex A. , Temple Larissa K. , Fleming Fergal J.
Published: November 2017

BACKGROUND:

It is unclear whether traveling long distances to high-volume centers would compensate for travel burden among patients undergoing rectal cancer resection.

OBJECTIVE:

The purpose of this study was to determine whether operative volume outweighs the advantages of being treated locally by comparing the outcomes of patients with rectal cancer treated at local, low-volume centers versus far, high-volume centers.

DESIGN:

This was a population-based study.

SETTINGS:

The National Cancer Database was queried for patients with rectal cancer.

PATIENTS:

Patients with stage II or III rectal cancer who underwent surgical resection between 2006 and 2012 were included.

MAIN OUTCOME MEASURES:

The outcomes of interest were margins, lymph node yield, receipt of neoadjuvant chemoradiation, adjuvant chemotherapy, readmission within 30 days, 30-day and 90-day mortality, and 5-year overall survival.

RESULTS:

A total of 18,605 patients met inclusion criteria; 2067 patients were in the long-distance/high-volume group and 1362 in the short-distance/low-volume group. The median travel distance was 62.6 miles for the long-distance/high-volume group and 2.3 miles for the short-distance/low-volume group. Patients who were younger, white, privately insured, and stage III were more likely to have traveled to a high-volume center. When controlled for patient factors, stage, and hospital factors, patients in the short-distance/low-volume group had lower odds of a lymph node yield ≥12 (OR = 0.51) and neoadjuvant chemoradiation (OR = 0.67) and higher 30-day (OR = 3.38) and 90-day mortality (OR = 2.07) compared with those in the long-distance/high-volume group. The short-distance/low-volume group had a 34% high risk of overall mortality at 5 years compared with the long-distance/high-volume group.

LIMITATIONS:

We lacked data regarding patient and physician decision making and surgeon-specific factors.

CONCLUSIONS:

Our results indicate that when controlled for patient, tumor, and hospital factors, patients who traveled a long distance to a high-volume center had improved lymph node yield, neoadjuvant chemoradiation receipt, and 30- and 90-day mortality compared with those who traveled a short distance to a low-volume center. They also had improved 5-year survival. See Video Abstract at http://links.lww.com/DCR/A446.
Couples' Experiences With Healthy Lifestyle Behaviors After Cardiac Rehabilitation
Authors: Rowland Sheri A. , Schumacher Karen L. , Leinen Dee Dee , Phillips Brenda G. , Schulz Paula S. , Yates Bernice C.
Published: November 2017

Purpose:

Many cardiac patients discontinue heart-healthy eating and physical activity (PA) behaviors in the months following cardiac rehabilitation (CR). Involving the spouse in CR with the patient may be 1 strategy to increase the maintenance of these behaviors after CR. Assisting patients and spouses with the maintenance of healthy eating and PA behavior following CR begins with a better understanding of the couple-focused factors, impacting their experiences with these behaviors. The purpose of this study was to qualitatively examine couple-focused facilitators and barriers to maintaining changes in healthy eating and PA behavior from the perspectives of both cardiac patients and their spouses following phase 2 CR.

Methods:

A purposive sample of 11 couples (patients undergoing postcoronary artery bypass graft surgery and their spouses) were selected from a larger randomized control trial. Semistructured, in-person interviews were conducted with patients and their spouses separately following CR. Data were analyzed using line-by-line coding to identify facilitator and barrier themes.

Results:

Two couple-focused barrier themes emerged: unnegotiated situations and unshared behaviors. Two couple-focused facilitator themes emerged: supportive exchanges and partnerships.

Conclusion:

These findings will help guide interventions targeting changes in diet and PA behavior in both patients and their spouses through minimizing unnegotiated situations, fostering supportive exchanges, and creating a partnership for the couple to work together on shared diet and PA goals. Targeting both patients and their spouses may be an innovative and effective way to intervene to increase adherence to healthy eating and PA behaviors post-CR.
PREDICTIVE FACTORS OF SURGICAL OUTCOMES IN VITRECTOMY FOR MYOPIC TRACTION MACULOPATHY
Authors: Hattori Kyoko , Kataoka Keiko , Takeuchi Jun , Ito Yasuki , Terasaki Hiroko
Published: November 2017

Purpose:

To assess predictive factors and surgical outcomes for myopic traction maculopathy.

Methods:

This retrospective observational case study enrolled 73 patients who underwent vitrectomy for myopic traction maculopathy. The 79 eyes obtained from our study sample were divided into 4 types: retinoschisis, lamellar macular hole (lamellar MH), foveal retinal detachment (FRD), and FRD + lamellar MH, or into 2 types according to the presence of FRD preoperatively. Dependent variables of interest were age, sex, pre- and postoperative best-corrected visual acuity (BCVA) at 6 months, and axial length.

Results:

All the four types showed moderately strong-to-strong positive correlations with pre- and postoperative BCVA (retinochisisi: r = 0.61; lamellar MH: r = 0.62; FRD: r = 0.51; FRD + lamellar MH; r = 0.83). Preoperative BCVA was associated with postoperative BCVA (P < 0.0001), but age, axial length, and the types of preoperative foveal status were not. Eyes with FRD had significantly worse pre- and postoperative BCVA than eyes without FRD (P = 0.036 and P = 0.046, respectively). Postoperative full-thickness macular holes developed in 5.1% of cases and in all types but retinoschisis.

Conclusion:

Preoperative visual acuity and the presence of FRD should be considered for surgical indication of myopic traction maculopathy.
AN ELDERLY PATIENT WITH ACUTE TRANSIENT OUTER RETINAL DISRUPTION RESEMBLING BILATERAL MULTIPLE EVANESCENT WHITE DOT SYNDROME
Authors: Golshani Cyrus , Gal-Or Orly , Giovinazzo Vincent , Freund K. Bailey
Published: November 2017

Purpose:

To report an unusual case of an elderly patient with transient outer retinal disruption resembling bilateral multiple evanescent white dot syndrome.

Methods:

Observational case report. Fundus photographs, fluorescein angiography, standard and ultra–widefield fundus autofluorescence, and cross-sectional and en face optical coherence tomography were used to characterize and describe the clinical findings.

Results:

A 67-year-old woman presented with decreased vision and floaters in her left eye. Best-corrected visual acuity was 20/20-3 in the right eye and 20/80-2 in the left eye. Funduscopic examination showed small deep white dots and foveal granularity of the left eye corresponding to hyperautofluorescent spots on fundus autofluorescence and ellipsoid zone disruption on spectral domain optical coherence tomography. The asymptomatic right eye had evidence of subretinal deposits on spectral domain optical coherence tomography but was otherwise unremarkable. At 4-week follow-up, the patient noted resolution of her symptoms in the left eye but had developed floaters and blurry vision in her right eye. The left eye showed resolving white spots and ellipsoid zone disruption. However, the right eye had new evidence of white spots corresponding to hyperautofluorescent spots on fundus autofluorescence. Spectral domain optical coherence tomography demonstrated subretinal deposits overlying areas of ellipsoid zone disruption. At 8-week follow-up, the patient was asymptomatic in both eyes with best-corrected visual acuity of 20/20 in both eyes. The hyperautofluorescent spots on ultra–widefield fundus autofluorescence had faded with restoration of ellipsoid zone disruption in both eyes and disappearance of subretinal deposits.

Conclusion:

Our case demonstrates multimodal retinal imaging findings resembling multiple evanescent white dot syndrome in an elderly patient. The bilateral presentation, presence of subretinal deposits before symptom onset, and older age of the patient were atypical features for this entity.
Estrogen Modulates Corneal Nociception and Maintains Corneal Homeostasis in Rat Eye
Authors: Kumar Vinod , Sur Vishma Pratap , Guha Rajdeep , Konar Aditya , Hazra Sarbani
Published: November 2017

Purpose:

To evaluate the role of estrogen in corneal nociception, its influence on lacrimal secretion, and development of dry eye.

Methods:

Ovariectomy was performed in normal healthy female rats (OVX). Estrogen replacement was performed in a population of these rats (OVX+E). Tests for dry eye and corneal sensitivity were performed and compared with rats in proestrus (PRO) as controls. Gene expression of neuropeptides such as substance P, calcitonin gene receptor-like protein (CGRP), estrogen receptor α, TRPV1, and TRPM8 was evaluated in the cornea and trigeminal ganglion. Expression of substance P and CGRP in the cornea was also examined by immunohistochemistry. The response of the cornea to capsaicin and menthol was evaluated to identify the activity of receptors TRPV1 and TRPM8, respectively.

Results:

There was a significant decrease in tear formation (4.2 ± 0.6 mm/min vs. 6.6 ± 0.42 mm/min), corneal sensitivity (2.2 ± 0.17 cm vs. 6 ± 0 cm), and increase in fluorescein staining in corneas after ovariectomy compared with controls. There was a significant decrease in gene expression of CGRP, substance P, TRPV1, and TRPM8 in the ovarioectomized cornea. A significant decrease in tear formation (3.17 ± 0.30 mm/min vs. 7.17 ± 0.87 mm/min) and eye wipe response (10.5 ± 1.99 wipes vs. 18.33 ± 1.05 wipes) after treatment with menthol and capsaicin in OVX rats was observed. Estrogen replacement significantly enhanced tear formation (4.02 ± 0.6 mm/min vs. 6.7 ± 0.80 mm/min), corneal sensitivity (2.2 ± 0.17 cm vs. 3.2 ± 0.17 cm), and response to capsaicin (10.5 ± 1.99 eye wipes vs. 24.5 ± 0.92 wipes) and menthol (3.17 ± 0.30 mm/min vs. 6.5 ± 0.22 mm/min) and increased expression of neuropeptides, TRPV1 and TRPM8.

Conclusions:

This study demonstrates the role of estrogen in corneal nociception and its deficiency as a cause of dry eye.
Coordination of Gaze Behavior and Foot Placement During Walking in Persons With Glaucoma
Authors: Miller Andreas B. , Lajoie Kim , Strath Robert A. , Neima David R. , Marigold Daniel S.
Published: November 2017

Purpose:

Vision normally provides environmental information necessary to direct the foot to safe locations during walking. Peripheral visual field loss limits what a person can see, and may alter how a person visually samples the environment. Here we tested the hypothesis that the spatial-temporal coupling between gaze and stepping in a precision-based walking task is altered in persons with glaucoma, particularly under dual task situations, and results in reduced foot-placement accuracy.

Methods:

Twenty persons with glaucoma and 20 normally sighted controls performed a precision walking task that involved stepping to the center of 4 targets under 3 conditions: targets only, walking, and counting backwards to simulate a conversation, and walking while performing a concurrent visual search task to simulate locating a landmark. We quantified foot-placement error and error variability with respect to the targets, as well as saccade and fixation timing with respect to foot placement.

Results:

Compared with controls, persons with glaucoma looked earlier at future stepping targets (with respect to toe-off of the foot) in the targets only and count conditions, and transferred gaze away sooner from the current stepping target in all conditions (P<0.05). Persons with glaucoma also had increased foot-placement error, particularly in the count condition, and increased foot-placement error variability compared with normally sighted controls (P<0.05).

Conclusions:

Glaucoma significantly disrupts gaze-foot coordination and results in less accurate foot placement when precision is required during walking. This may increase the risk of trips and falls in this population.
Risk Factors for Earlier Reexposure of Glaucoma Drainage Devices
Authors: Thompson Atalie C. , Manjunath Varsha , Muir Kelly W.
Published: November 2017

Purpose:

The purpose of this study was to investigate factors associated with a second exposure of a glaucoma drainage device (GDD) following repair of an initial GDD exposure.

Materials and Methods:

This IRB-approved retrospective cohort study examined the incidence of a second exposure of a GDD following initial repair for exposure. Logistic regression was performed to assess the relationship between demographic and clinical characteristics and a second exposure of the GDD. Kaplan-Meier survival curves were plotted and Cox regression was performed to examine factors impacting the time to a second GDD exposure.

Results:

Ninety-four eyes of subjects that underwent initial revision for GDD exposure were reviewed. Approximately 44% (N=41/94) of subjects underwent surgical revision for a second exposure. Factors associated with reexposure in multivariate logistic regression included caucasian race (odds ratio, 2.99; P=0.02) and use of a nonscleral patch graft (odds ratio, 2.93; P=0.019). Time from revision of the initial exposure to reexposure was significantly shorter for those with a nonscleral patch graft (hazard ratio, 2.23; P=0.01) and caucasian race (hazard ratio, 2.08; P=0.04).

Conclusions:

Caucasian race and use of a nonscleral patch graft during revision surgery was associated with a higher risk of experiencing a sooner reexposure of the GDD following revision of an initial exposure. Future studies should examine whether particular graft materials increase the risk of GDD reexposure.
A prospective case of postherpetic itch monitored by quantitative sensory testing for 1 year while undergoing 8% topical capsaicin treatments
Authors: Andersen Hjalte H. , Arendt-Nielsen Lars , Yosipovitch Gil , Elberling Jesper
Published: November 2017

Following reactivation of a latent ganglionic varicella zoster virus and skin eruption in the corresponding dermatome(s) ∼20% of patients develop chronic postherpetic neuralgia. A subset of these patients develop severe and often intractable chronic postherpetic itch in the affected area. However, this is rarely studied and little is known about its epidemiology, pathogenesis, and management. In this case study we followed a patient with moderate to severe chronic postherpetic itch characterized by pure itch sensation, using standardized quantitative sensory testing and observed a profound loss-of-function for C-fibers, Aδ-fibers, and Aβ-fibers within the affected area. The testing was conducted before, during, and after 8% topical capsaicin treatments applied in 4 cycles (3 months apart) over the course of ∼1 year. During this period the hypoesthesia gradually normalized, but heat hypoalgesia remained unchanged. The 8% topical capsaicin had a good and long lasting antipruritic effect eventually resulting in complete resolution of the itch in parallel with partial recovery of initial hypoesthesia, particularly for warmth and cold detection, likely unrelated to the treatments.
Endoscopic Sciatic Nerve Decompression After Fracture or Reconstructive Surgery of the Acetabulum in Comparison With Endoscopic Treatments in Idiopathic Deep Gluteal Syndrome
Authors: Park Myung-sik , Jeong Seong-Yep , Yoon Sun-Jung
Published: November 2017

Objective:

The purpose of this study was to assess the endoscopic findings of the sciatic nerve and clinical outcomes of major traumatic sciatic nerve neuropathies after fracture or reconstructive surgery of the acetabulum with idiopathic deep gluteal syndrome (DGS) groups.

Design:

Retrospective review of patient reports.

Setting:

Level I trauma center of a tertiary university hospital.

Participants:

The study included 70 patients who consecutively underwent endoscopic sciatic nerve decompression. Patients who had previous fractures or reconstructive surgeries of the acetabulum were categorized as the major trauma group, whereas those without major trauma were categorized as the idiopathic group (45 patients) after a minimum of 24-months of follow-up period.

Main Outcome Measures:

The results were evaluated using the modified Harris Hip Score (mHHS), Hip outcome, and 12-Item Short Form Health Survey scores, respectively.

Results:

In the major trauma group, all patients with sensory symptoms showed some degree of relief after the endoscopic sciatic nerve release. None of the patients with complete foot drop demonstrated complete improvement. Three patients with motor weakness without foot drop showed complete improvement in motor function. The mean mHHS increased from 61.5 ± 13.4 to 84.1 ± 8.1 (P = 0.031). In the idiopathic DGS group, the mean mHHS increased from 73.8 ± 10.3 to 94.4 ± 5.3 (P = 0.003). The Benson outcomes rating in the major trauma group was statistically lower than that in the idiopathic DGS group.

Conclusion:

Endoscopic release of the sciatic nerve after fractures or reconstructive surgeries could provide some improvements without complications. However, more favorable outcomes were observed in the idiopathic DGS group.
Effects of Intravenous Cold Saline on Hyperthermic Athletes Representative of Large Football Players and Small Endurance Runners
Authors: Morrison Katherine E. , Desai Natasha , McGuigan Christopher , Lennon Megan , Godek Sandra Fowkes
Published: November 2017

Objective:

To evaluate the cooling effects of intravenous (IV) cold normal (0.9%) saline on hyperthermic athletes.

Design:

Randomized crossover study design.

Setting:

Controlled research laboratory.

Participants:

Twelve male participants who were representative of a collegiate cross-country (6) and American football (6) population.

Interventions:

Participants underwent body composition analysis using a BodPod. They were placed in an environmentally controlled chamber and brought to a Tc of 39.5°C with dynamic exercise. When temperatures were reached, they were treated with either 2 L of cold saline (CS) (4°C) or intravenous room temperature (22°C) saline (RS) over a ∼30-minute period. Tre was measured with a rectal temperature probe every minute during the treatment period.

Main Outcome Measures:

Total ΔTre (ending Tre − starting Tre) and cooling rate (total change in Tre/time) were measured for each condition, and body composition variables calculated included body surface area (BSA), BSA-to-mass ratio (BSA/mass), lean body mass, and body fat percentage (%BF) (P < 0.05).

Results:

Statistically significant differences were found in the total ΔTre and cooling rate between the CS and RS trials. The cooling rate for the CS trials was significantly correlated to mass, BSA, BSA/mass, and %BF.

Conclusions:

In hyperthermic athletes, core temperature was reduced more effectively using chilled saline during IV infusion. Body composition had a significant impact on overall cooling revealing that the smaller and leaner participants cooled at a greater rate. When indicated, CS infusion could be considered for cooling hyperthermic individuals when other methods are not available.
The Role of Immunoglobulin in the Treatment of Immune-Mediated Peripheral Neuropathies
Authors: Tobon Alejandro
Published: November 2017

Immune-mediated neuropathies are a group of peripheral nerve disorders characterized by motor or sensory deficits caused by inflammation leading to demyelination or axonal injury. Intravenous immunoglobulin (IVIg) has been demonstrated to be an effective therapy for the 3 most common immune-mediated neuropathies: Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, and multifocal motor neuropathy. This review summarizes current data on the rationale for the use of IVIg in immune-mediated neuropathies, addressing mechanism of action, clinical evidence, and practical considerations for its use.
Rheumatoid Arthritis
Authors: Kirchner Elizabeth
Published: November 2017

Approximately 1 in 5 people in the United States suffers from autoimmune diseases. To explain the pathophysiology of autoimmune disease, a basic understanding of the normal and dysfunctional immune system is necessary. Rheumatoid arthritis is used as a model to explain the basics of autoimmune disease. The infusion nurse plays a key role in patient education and the safe administration of biologics.
Improving Quality of Chest Radiographs After Placement of Peripherally Inserted Central Catheters
Authors: Jones Jill , Meek Lucas , Best Shaun , McCann Amy , Welsh Brandon , Hill Jacqueline , Ash Ryan
Published: November 2017

The goal of this study was to determine the best method for localizing peripherally inserted central catheters (PICCs) in postplacement portable chest radiographs. A retrospective analysis showed no significant difference in visualization of the PICC tip between different chest radiograph projections. Modifications were made to an institutional PICC protocol to obtain anteroposterior chest views with the guidewire present only. Repeat analysis demonstrated statistically significant increases in the frequency of anteroposterior radiographs performed, the number of chest radiographs with guidewire, and the localization of the catheter. By standardizing the acquisition of PICC placement chest radiographs, fewer variant projection radiographs were performed and the catheter tip was confidently localized in more examinations.
Trajectories of Anxiety and Depression After Liver Transplantation as Related to Outcomes During 2-Year Follow-Up: A Prospective Cohort Study
Authors: Annema Coby , Drent Gerda , Roodbol Petrie F. , Stewart Roy E. , Metselaar Herold J. , van Hoek Bart , Porte Robert J. , Ranchor Adelita V.
Published: November 2017

Objective

The aims of the study were to examine whether distinct trajectories of anxious and depressive symptoms are present among liver transplant recipients from before transplantation to 2 years afterward, to identify associated demographic, clinical, and individual characteristics, and to examine the influence of distinct trajectories on outcomes.

Methods

A prospective, multicenter cohort study was performed among 153 liver transplant recipients. Data were retrieved using questionnaires administered before transplantation and at 3, 6, 12, and 24 months after transplantation. Clinical data were retrieved by medical record review. Latent class growth analysis was used to identify distinct trajectories. χ2 test, analyses of variance, and multinomial logistic regression were used to identify associated variables and the impact of the distinct trajectories on outcomes.

Results

Three distinct trajectories for symptoms of anxiety (State-Trait Anxiety Inventory-short form) as well as depression (Center for Epidemiological Studies Depression Scale) were identified: “no symptoms,” “resolved symptoms,” and “persistent symptoms.” The trajectories of persistent anxiety and depression comprised, respectively, 23% and 29% of the transplant recipients. Several clinical and individual variables were associated with the trajectories of persistent anxiety and/or depression: experiencing more adverse effects of the immunosuppressive medication, lower level of personal control, more use of emotion-focused coping, less disclosure about the transplant, and more stressful life events. The trajectories of persistent symptoms were associated with worse outcomes regarding medication adherence and health-related quality of life, but not with mortality.

Conclusions

A significant subset of transplant recipients showed persistent symptoms of anxiety and depression from before to 2 years after transplantation. These results emphasize the importance of psychosocial care in the transplant population.
The Clinician Faced With Anticochlear Antibodies: What to Do With Them?
Authors: Carlomagno Adriana , Silveira Gonzalo , Rebella Martín , Vola Magdalena , Danza Alvaro
Published: November 2017

Background

Autoimmune inner ear disease as a cause of sensorineural hearing loss is a poorly understood entity. Thus, the role of anticochlear antibodies (ACLAs) in clinical management is still not well established.

Objective

The aims of this study were to describe the use of ACLAs in our clinical setting and to understand the clinicians' therapeutic approach in these cases. We also analyzed the usefulness of these autoantibodies in clinical practice.

Methods

A retrospective study with nonprobabilistic convenience sampling of patients who were tested for ACLAs in the period from January 1, 2013, to December 31, 2015, was performed. The study was carried out in 2 stages: (1) medical records of all patients who were investigated for ACLAs were reviewed. The following variables were analyzed: age, sex, reason for requesting ACLAs, concomitant autoimmune disease, audiogram, immunosuppressive treatment, duration of treatment, and clinical response; (2) patients who received immunosuppressive therapy were contacted by telephone. A visual analog scale (VAS) (0–10) was applied to evaluate the therapeutic response.

Results

Thirty-nine patients who were investigated for ACLAs were identified. The mean age was 41 (SD, 16) years; there were 33 female patients. Of the 34 patients with ACLA-positive antibodies, 16 patients received immunosuppressive agents, of for management of their sensorineural hearing loss, corticosteroids was the most commonly used treatment. No clinical improvement was reported by patients after immunosuppressive treatment in this subgroup.

Conclusions

The role of ACLAs in the diagnosis and management of sensorineural hearing loss remains unclear. In this small study at a single institution, ACLA testing may not have improved the outcome of sensorineural hearing loss.
Assessment of Fetal Congenital Heart Diseases by 4-Dimensional Ultrasound Using Spatiotemporal Image Correlation
Authors: Araujo Júnior Edward , Tonni Gabriele , Bravo-Valenzuela Nathalie Jeanne , Da Silva Costa Fabricio , Meagher Simon
Published: November 2017

The aim of this pictorial review is to describe the technical advances achieved through the application of 4-dimensional (4D) ultrasound using spatiotemporal image correlation (STIC) over conventional 2-dimensional ultrasound in the prenatal detection of congenital heart disease (CHD). Spatiotemporal image correlation is a volume imaging technique that simplifies fetal heart studies while providing more diagnostic information than is typically available from traditional 2-dimensional studies. Four-dimensional software allows the study of cardiac anatomy and function during a single cardiac cycle and has greatly contributed to diagnostic enhancement of CHD. Color flow and power Doppler can be added to STIC in the study of vessel anatomy and to increase the detection of ventricular septal defects. Anatomical details of the fetus can be displayed in multiple images such as using computed tomography or magnetic resonance imaging. In addition, cardiac anatomy can be sectioned freely and reconstructed using different reformatting applications. Realistic views of the fetal heart, with particular emphasis on myocardium and endocardium cushion, can be reached using novel lightening techniques. Moreover, using 4D ultrasound, echolucent structures can be converted into solid voxels generating “digital casts” of the fetal heart that enhances the understanding of the great vessel relationships in the ventricular inflow and outflow tracts. Recently, sillhouette mode has shown to improve depth perception and resolution compared with conventional 3D power Doppler in the study of inflow and outflow tracts. Here, a gallery of prenatally detected CHD using 4D ultrasound with STIC and different applications is described.
Prediction of 60-Day Case Fatality in Critically Ill Patients Receiving Renal Replacement Therapy: External Validation of a Prediction Model
Authors: Carvalho Gloria Maria Custodio de , Leite Tacyano Tavares , Libório Alexandre Braga
Published: November 2017

Background:

A recent prognostic model, predicting 60-day case fatality in critically ill patients requiring renal replacement therapy (RRT), has been developed (Acute Renal Failure Trial Network [ATN] study). Because many prognostic models are suggested in literature, but just a few have found its way into clinical practice, we aimed to externally validate this prediction model in an independent cohort.

Methods:

A total of 1,053 critically ill patients requiring RRT from the MIMIC-III database were analyzed. The models’ discrimination was evaluated using c-statistics. Calibration was evaluated by Hosmer–Lemeshow (H–L) test and GiViTi calibration belt.

Results:

In a case-mix population, including patients with normal or altered serum creatinine (sCr) at intensive care unit admission, discrimination was moderate, with a c-statistic of 0.71 in the nonintegerized risk model. In patients with altered baseline sCr, better discrimination was achieved with the integer risk model (0.76, 95% confidence interval, 0.71–0.81). As for the calibration, although the H–L test was good only in patients with normal/slightly altered sCr at admission, the calibration belt disclosed no significant deviations from the bisector line for any of the models in patients, regardless of admission sCr. Of note, a refitted model had a c-statistics of 0.85, similar to the derivation cohort.

Conclusions:

The ATN prognostic model can be useful in a broad cohort of critically ill patients. Although it showed only moderate discrimination capacity when patients with elevated admission sCr were included, using a refitted model improved it, illustrating the need for continuous external validation and updating of prognostic models over time before their implementation in clinical practice.
Low recombination rates in sexual species and sex–asex transitions
Authors: Haag Christoph R. , Theodosiou Loukas , Zahab Roula , Lenormand Thomas
Published: November 2017

In most sexual, diploid eukaryotes, at least one crossover occurs between each pair of homologous chromosomes during meiosis, presumably in order to ensure proper segregation. Well-known exceptions to this rule are species in which one sex does not recombine and specific chromosomes lacking crossover. We review other possible exceptions, including species with chromosome maps of less than 50 cM in one or both sexes. We discuss the idea that low recombination rates may favour sex–asex transitions, or, alternatively may be a consequence of it. We then show that a yet undescribed species of brine shrimpArtemiafrom Kazakhstan (A. sp. Kazakhstan), the closest known relative of the asexualArtemia parthenogenetica, has one of the shortest genetic linkage maps known. Based on a family of 42 individuals and 589 RAD markers, we find that many linkage groups are considerably shorter than 50 cM, suggesting either no obligate crossover or crossovers concentrated at terminal positions with little effect on recombination. We contrast these findings with the published map of the more distantly related sexual congener,A. franciscana, and conclude that the study of recombination in non-model systems is important to understand the evolutionary causes and consequences of recombination.

This article is part of the themed issue ‘Evolutionary causes and consequences of recombination rate variation in sexual organisms’.
The consequences of sequence erosion in the evolution of recombination hotspots
Authors: Tiemann-Boege Irene , Schwarz Theresa , Striedner Yasmin , Heissl Angelika
Published: November 2017

Meiosis is initiated by a double-strand break (DSB) introduced in the DNA by a highly controlled process that is repaired by recombination. In many organisms, recombination occurs at specific and narrow regions of the genome, known as recombination hotspots, which overlap with regions enriched for DSBs. In recent years, it has been demonstrated that conversions and mutations resulting from the repair of DSBs lead to a rapid sequence evolution at recombination hotspots eroding target sites for DSBs. We still do not fully understand the effect of this erosion in the recombination activity, but evidence has shown that the binding oftrans-acting factors like PRDM9 is affected. PRDM9 is a meiosis-specific, multi-domain protein that recognizes DNA target motifs by its zinc finger domain and directs DSBs to these target sites. Here we discuss the changes in affinity of PRDM9 to eroded recognition sequences, and explain how these changes in affinity of PRDM9 can affect recombination, leading sometimes to sterility in the context of hybrid crosses. We also present experimental data showing that DNA methylation reduces PRDM9 bindingin vitro. Finally, we discuss PRDM9-independent hotspots, posing the question how these hotspots evolve and change with sequence erosion.

This article is part of the themed issue ‘Evolutionary causes and consequences of recombination rate variation in sexual organisms’.
The Red Queen model of recombination hot-spot evolution: a theoretical investigation
Authors: Latrille Thibault , Duret Laurent , Lartillot Nicolas
Published: November 2017

In humans and many other species, recombination events cluster in narrow and short-lived hot spots distributed across the genome, whose location is determined by the Zn-finger protein PRDM9. To explain these fast evolutionary dynamics, an intra-genomic Red Queen model has been proposed, based on the interplay between two antagonistic forces: biased gene conversion, mediated by double-strand breaks, resulting in hot-spot extinction, followed by positive selection favouring new PRDM9 alleles recognizing new sequence motifs. Thus far, however, this Red Queen model has not been formalized as a quantitative population-genetic model, fully accounting for the intricate interplay between biased gene conversion, mutation, selection, demography and genetic diversity at the PRDM9 locus. Here, we explore the population genetics of the Red Queen model of recombination. A Wright–Fisher simulator was implemented, allowing exploration of the behaviour of the model (mean equilibrium recombination rate, diversity at the PRDM9 locus or turnover rate) as a function of the parameters (effective population size, mutation and erosion rates). In a second step, analytical results based on self-consistent mean-field approximations were derived, reproducing the scaling relations observed in the simulations. Empirical fit of the model to current data from the mouse suggests both a high mutation rate at PRDM9 and strong biased gene conversion on its targets.

This article is part of the themed issue ‘Evolutionary causes and consequences of recombination rate variation in sexual organisms’.
The impact of recombination on human mutation load and disease
Authors: Alves Isabel , Houle Armande Ang , Hussin Julie G. , Awadalla Philip
Published: November 2017

Recombination promotes genomic integrity among cells and tissues through double-strand break repair, and is critical for gamete formation and fertility through a strict regulation of the molecular mechanisms associated with proper chromosomal disjunction. In humans, congenital defects and recurrent structural abnormalities can be attributed to aberrant meiotic recombination. Moreover, mutations affecting genes involved in recombination pathways are directly linked to pathologies including infertility and cancer. Recombination is among the most prominent mechanism shaping genome variation, and is associated with not only the structuring of genomic variability, but is also tightly linked with the purging of deleterious mutations from populations. Together, these observations highlight the multiple roles of recombination in human genetics: its ability to act as a major force of evolution, its molecular potential to maintain genome repair and integrity in cell division and its mutagenic cost impacting disease evolution.

This article is part of the themed issue ‘Evolutionary causes and consequences of recombination rate variation in sexual organisms’.
Connecting theory and data to understand recombination rate evolution
Authors: Dapper Amy L. , Payseur Bret A.
Published: November 2017

Meiotic recombination is necessary for successful gametogenesis in most sexually reproducing organisms and is a fundamental genomic parameter, influencing the efficacy of selection and the fate of new mutations. The molecular and evolutionary functions of recombination should impose strong selective constraints on the range of recombination rates. Yet, variation in recombination rate is observed on a variety of genomic and evolutionary scales. In the past decade, empirical studies have described variation in recombination rate within genomes, between individuals, between sexes, between populations and between species. At the same time, theoretical work has provided an increasingly detailed picture of the evolutionary advantages to recombination. Perhaps surprisingly, the causes of natural variation in recombination rate remain poorly understood. We argue that empirical and theoretical approaches to understand the evolution of recombination have proceeded largely independently of each other. Most models that address the evolution of recombination rate were created to explain the evolutionary advantage of recombination rather than quantitative differences in rate among individuals. Conversely, most empirical studies aim to describe variation in recombination rate, rather than to test evolutionary hypotheses. In this Perspective, we argue that efforts to integrate the rich bodies of empirical and theoretical work on recombination rate are crucial to moving this field forward. We provide new directions for the development of theory and the production of data that will jointly close this gap.

This article is part of the themed issue ‘Evolutionary causes and consequences of recombination rate variation in sexual organisms’.
Background selection as null hypothesis in population genomics: insights and challenges fromDrosophilastudies
Authors: Comeron Josep M.
Published: November 2017

The consequences of selection at linked sites are multiple and widespread across the genomes of most species. Here, I first review the main concepts behind models of selection and linkage in recombining genomes, present the difficulty in parametrizing these models simply as a reduction in effective population size (Ne) and discuss the predicted impact of recombination rates on levels of diversity across genomes. Arguments are then put forward in favour of using a model of selection and linkage with neutral and deleterious mutations (i.e. the background selection model, BGS) as a sensible null hypothesis for investigating the presence of other forms of selection, such as balancing or positive. I also describe and compare two studies that have generated high-resolution landscapes of the predicted consequences of selection at linked sites inDrosophila melanogaster. Both studies show that BGS can explain a very large fraction of the observed variation in diversity across the whole genome, thus supporting its use as null model. Finally, I identify and discuss a number of caveats and challenges in studies of genetic hitchhiking that have been often overlooked, with several of them sharing a potential bias towards overestimating the evidence supporting recent selective sweeps to the detriment of a BGS explanation. One potential source of bias is the analysis of non-equilibrium populations: it is precisely because models of selection and linkage predict variation inNeacross chromosomes that demographic dynamics are not expected to be equivalent chromosome- or genome-wide. Other challenges include the use of incomplete genome annotations, the assumption of temporally stable recombination landscapes, the presence of genes under balancing selection and the consequences of ignoring non-crossover (gene conversion) recombination events.

This article is part of the themed issue ‘Evolutionary causes and consequences of recombination rate variation in sexual organisms’.
Recombinant expression and characterisation of the oxygen-sensitive 2-enoate reductase from Clostridium sporogenes
Authors: Mordaka Pawel M. , Hall Stephen J. , Minton Nigel , Stephens Gill
Published: November 2017

‘Ene’-reductases have attracted significant attention for the preparation of chemical intermediates and biologically active products. To date, research has been focussed primarily on Old Yellow Enzyme-like proteins, due to their ease of handling, whereas 2-enoate reductases from clostridia have received much less attention, because of their oxygen sensitivity and a lack of suitable expression systems. A hypothetical 2-enoate reductase gene, fldZ, was identified in Clostridium sporogenes DSM 795. The encoded protein shares a high degree of homology to clostridial FMN- and FAD-dependent 2-enoate reductases, including the cinnamic acid reductase proposed to be involved in amino acid metabolism in proteolytic clostridia. The gene was cloned and overexpressed in Escherichia coli. Successful expression depended on the use of strictly anaerobic conditions for both growth and enzyme preparation, since FldZ was oxygen-sensitive. The enzyme reduced aromatic enoates, such as cinnamic acid or p-coumaric acid, but not short chain unsaturated aliphatic acids. The β,β-disubstituted nitroalkene, (E)-1-nitro-2-phenylpropene, was reduced to enantiopure (R)-1-nitro-2-phenylpropane with a yield of 90 %. By contrast, the α,β-disubstituted nitroalkene, (E)-2-nitro-1-phenylpropene, was reduced with a moderate yield of 56 % and poor enantioselectivity (16 % ee for (S)-2-nitro-1-phenylpropane). The availability of an expression system for this recombinant clostridial 2-enoate reductase will facilitate future characterisation of this unusual class of ‘ene’-reductases, and expand the biocatalytic toolbox available for enantioselective hydrogenation of carbon-carbon double bonds.
Crystal structures of (E)-1-{3-[(5-fluoro-2-hydroxybenzylidene)amino]phenyl}ethanone and of a fourth polymorph of (E)-1-{3-[(2-hydroxy-3-methoxybenzylidene)amino]phenyl}ethanone
Authors: Girisha Marisiddaiah , Yathirajan Hemmige S. , Rathore Ravindranath S. , Glidewell Christopher
Published: November 2017

In the molecules of both (E)-1-{3-[(5-fluoro-2-hydroxybenzylidene)amino]phenyl}ethanone, C15H12FNO2, (I), and (E)-1-{3-[(2-hydroxy-3-methoxybenzylidene)amino]phenyl}ethanone, C16H15NO3, (II), which crystallizes withZ′ = 2 in space groupPca21, there are intramolecular O—H...N hydrogen bonds, and the non-H atoms in each molecule are essentially coplanar. In the crystal of (I), molecules are linked by a single C—H...O hydrogen bond to form aC(8) chain, whereas in the crystal of (II), molecules are linked by three C—H...O hydrogen bonds to form sheets within which orthogonalC22(16) andC22(17) chains can be identified. Comparisons are made with some related structures.