bluuebunny/crossref_metadata_2025 huggingface dataset:
Docking of the Femoral Head Following Closed Reduction for DDH: Does it Really Occur?
Authors: Talathi Nakul S. , Chauvin Nancy A. , Sankar Wudbhav N.
Published: June 2018

Background:

It has been suggested that the femoral head can “dock” deeper into the acetabulum after initial closed reduction (CR) for developmental dysplasia of the hip (DDH). The purpose of this study was to quantify the interval change in femoral head position between immediate postoperative magnetic resonance imaging (MRI) and follow-up imaging at ~3 weeks.

Methods:

A retrospective review of 29 patients (30 hips) who underwent CR and spica casting for DDH was conducted. Immediate postoperative and average 3-week follow-up MRI scans in spica were performed on all patients. On both scans, 2 blinded reviewers measured the following indices: the distance between the femoral head and the acetabulum on midcoronal and midaxial images, the displacement of the center of femoral head from Hilgenreiner’s line in the coronal and axial plane, and the left-right displacement of the center of femoral head from Perkins line. Measurements were averaged between the 2 reviewers and the interval change in femoral head position between the immediate postoperative and follow-up scans were compared.

Results:

There were 26 female individuals and 3 male individuals in our series with a mean age of 7.6 months (range, 4 to 13 mo). Follow-up MRI scans were performed at an average of 23.8 days (range, 13 to 46 d). On the basis of the averaged measurements from both readers, the distance between the femoral head and the acetabulum decreased significantly on coronal measurement and on all 3 axial measurements between initial and follow-up MRI. In addition, the position of the femoral head became significantly more medial, more anterior, and more cranial relative to the acetabulum. The interrater correlation coefficient between both readers across all measurements was 0.731.

Conclusions:

These findings provide evidence that femoral head position within the acetabulum improves even over a short time period following initial CR for DDH, suggesting that the “docking” phenomenon may in fact occur.

Level of Evidence:

Level IV—therapeutic study.
Anxiety, depressive symptoms, and cardiac autonomic function in perimenopausal and postmenopausal women with hot flashes: a brief report
Authors: Fu Polly , Gibson Carolyn J. , Mendes Wendy Berry , Schembri Michael , Huang Alison J.
Published: June 2018

Objective:

The aim of the study was to examine whether anxiety and depressive symptoms are associated with an adverse cardiac autonomic profile among midlife women with hot flashes.

Methods:

Anxiety and depressive symptoms were evaluated by validated self-administered questionnaires among peri- and postmenopausal women in a randomized trial of slow-paced respiration for hot flashes. Pre-ejection period (PEP), a marker of sympathetic activation, and respiratory sinus arrhythmia (RSA), a marker of parasympathetic activation, were measured at baseline and 12 weeks using impedance cardiography and electocardiography. Multivariable repeated measures linear regression models examined associations between anxiety and depression symptoms and autonomic markers, corrected for multiple comparisons with Benjamini–Hochberg procedure, and adjusted for age and body mass index.

Results:

Among the 121 participants, greater state anxiety was associated with shorter PEP, reflecting higher sympathetic activity (β = −0.24,P = 0.02). Greater trait anxiety and cognitive anxiety were associated with lower RSA, reflecting decreased parasympathetic activity (β = −0.03,P < 0.01 for Spielberger Trait Anxiety;β = −0.06,P = 0.02 for Hospital Anxiety and Depression Scale [HADS] Anxiety Subscale). Greater depressive symptoms were associated with lower RSA (β = −0.06,P = 0.03 for HADS Depression Subscale;β = −0.03,P = 0.04 for Beck Depression Inventory).

Conclusions:

Among peri- and postmenopausal women with hot flashes, greater self-reported anxiety and depressive symptoms were associated with lower levels of resting cardiac parasympathetic activity, and greater state anxiety was associated with higher levels of cardiac sympathetic activity. Findings suggest that midlife women with increased anxiety and depressive symptoms may have an unfavorable cardiac autonomic profile with potential implications for their overall cardiovascular risk.
Treatment Delay Impact on Open Reduction Internal Fixation of Mandibular Fractures: A Systematic Review
Authors: Stone Nicholas , Corneman Alex , Sandre Anthony R. , Farrokhyar Forough , Thoma Achilleas , Cooper Michael J.
Published: June 2018

Background:

The impact of mandible fracture treatment delay has been contested in the literature for decades, with conventional wisdom favoring earlier surgical treatment to prevent postoperative complications, primarily infection. Through a systematic review of all available evidence, this study aims to determine whether delay to open reduction and internal fixation of traumatic mandibular fractures influences outcomes.

Methods:

MEDLINE, EMBASE, CINAHL, and Web of Science were systematically searched for English language literature pertaining to the above research question and screened in duplicate. Methodological quality scoring was performed using MINORS criteria. Qualitative and quantitative findings from relevant studies are presented.

Results:

Twenty eligible studies including 2,671 patients had open reduction internal fixation, with or without adjunct mandibulomaxillary fixation. All studies were observational cohort or case-control studies of low methodological quality with a mean MINORS score of 6.5 of 16 (40.6%) for noncomparative studies and 11.2 of 24 (46.7%) for comparative studies. Only 5 of 20 (25%) studies recommended earlier treatment. Due to insufficient reporting of data and study heterogeneity, the impact of treatment delay on complications could not be quantitatively analyzed.

Conclusions:

There is substantial heterogeneity and no consensus on the definition of “early” versus “delayed” surgical treatment for patients with traumatic mandibular fractures. The majority of included studies do not make a recommendation for earlier treatment. Future, well-designed prospective studies are essential to determine if there is an optimal surgical treatment delay of mandibular fractures that mitigates the risk of infectious and noninfectious complications.
Acute Glaucoma Following Cyanoacrylate Glue Patch for Corneal Perforation
Authors: Vasquez-Perez Alfonso , Matarazzo Francesco , Mandal Niraj , Tuft Stephen
Published: June 2018

Purpose:

To describe a case of acute glaucoma after cyanoacrylate gluing for a nontraumatic central corneal perforation.

Methods:

A 55-year-old woman with history of rheumatoid arthritis and severe dry eye presented to emergency with a right central corneal perforation. She was treated successfully with the use cyanoacrylate glue patch but iridocorneal adhesions remained. The next day she presented with ocular pain, headaches, and vomiting. On examination she had shallow anterior chamber (AC) with no aqueous leakage but her intraocular pressure (IOP) was 56 mm Hg measured with rebound tonometry. An anterior segment optical coherence tomography scan showed a 360 degrees central iris adhesion with shallow AC. Topical and oral treatment for acute glaucoma was given that decreased her IOP. She then underwent urgent surgery to release the iridocorneal adhesions and restore aqueous flow that was achieved without replacing the glue patch.

Results:

One day postoperatively her right eye was comfortable and her IOP measurement remained within normal limits. The AC was deep with no iridocorneal adhesions.

Conclusions:

Close monitoring of the IOP is recommendable in central corneal perforations with iris adhesions managed with cyanoacrylate glue due to the potential developing of aqueous blockage.
A Systematic Review and Meta-Analysis on Outcomes and Complications of Percutaneous Endoscopic Versus Radiologic Gastrostomy for Enteral Feeding
Authors: Strijbos Denise , Keszthelyi Daniel , Bogie Roel M.M. , Gilissen Lennard P.L. , Lacko Martin , Hoeijmakers Janneke G.J. , van der Leij Christiaan , de Ridder Rogier , de Haan Michiel W. , Masclee Ad A.M.
Published: June 2018

Background:

The optimal technique for long-term enteral feeding has not yet been established. Both percutaneous endoscopic gastrostomy (PEG) and percutaneous radiologic gastrostomy (PRG) are widely used. Aim was to extensively review outcomes of PEG and PRG.

Materials and Methods:

A systematic review using Medline, Embase, and Cochrane was performed, using standardized tools for assessing bias. Main outcomes were infectious and tube-related complications, procedure related and 30-day mortality. Pooled risk differences (RDs) with corresponding 95% confidence intervals (95% CIs) were calculated using random effects. Arcsine transformations were applied.

Results:

In total, 344 studies were identified, of which 16 were included, reporting on 934 PEGs and 1093 PRGs. No differences were found for infectious complications [RD, 0.03 (−0.05 to 0.11)], procedure-related mortality [RD, 0.01 (−0.04 to 0.06)], or 30-day mortality [RD, 0.06 (−0.01 to 0.13)]. Tube-related complications were higher in PRG [RD, 0.16 (0.06-0.26)]. Subgroup analysis was performed for head and neck cancer (HNC) and motor neuron disease. In HNC, this revealed significantly lower tube-related complications and procedure-related mortality after PEG. In motor neuron disease, no differences were seen. The level of evidence appears sufficient considering the low degree of heterogeneity.

Conclusions:

No differences were found with regard to mortality or infectious complications. PEG showed lower risk of tube-related complications. Subgroup analysis revealed PEG to be favorable in HNC based on lower rates of procedure-related mortality and tube-related complications. Local experience and availability should be taken into account in the decision process.
Non-alcoholic fatty liver disease and hypertension: coprevalent or correlated?
Authors: Oikonomou Dimitrios , Georgiopoulos Georgios , Katsi Vassiliki , Kourek Chris , Tsioufis Constantinos , Alexopoulou Alexendra , Koutli Evaggelia , Tousoulis Dimitrios
Published: June 2018

Objective

To provide a comprehensive review summarizing the existing evidence on the association between nonalcoholic fatty liver disease (NAFLD) and hypertension (HT) independent of other components of metabolic syndrome.

Methods

We searched the literature through Medline and the Cochrane Library for studies evaluating the relationship between hypertension and fatty liver disease.

Results

Studies testing this association are limited, but agree that HT and fatty liver disease are inter-related independent of other components of the metabolic syndrome such as obesity and diabetes mellitus. Clinical evidence shows that NAFLD is associated with new-onset HT, whereas increased blood pressure is related to the development of fatty liver disease and the possible subsequent progression to liver fibrosis. Insulin resistance and activation of the renin–angiotensin–aldosterone system (RAAS) might provide potential pathophysiologic links between these clinical entities. Until further evidence is available, patients with HT should be meticulously evaluated and treated for fatty liver disease and vice versa. RAAS inhibitors have been tested in NAFLD, presenting a favorable profile by decreasing insulin resistance and fibrosis progression.

Conclusion

NAFLD and HT are associated independent of traditional cardiovascular risk factors. Insulin resistance appears to be the main linking mechanism. Although RAAS inhibitors are the most beneficial treatment option for HT in patients with NAFLD, randomized studies on the administration of these agents in HT patients with NAFDL are warranted to provide optimal treatment options in these high cardiovascular risk individuals.
Comparison of Clinical Methods With the Faecal Gluten Immunogenic Peptide to Assess Gluten Intake in Coeliac Disease
Authors: Gerasimidis Konstantinos , Zafeiropoulou Konstantina , Mackinder Mary , Ijaz Umer Z , Duncan Hazel , Buchanan Elaine , Cardigan Tracey , Edwards Christine A. , McGrogan Paraic , Russell Richard K.
Published: June 2018

Objectives:

Detection of faecal gluten immunogenic peptides (GIP) is a biomarker of recent gluten consumption. GIP levels can be used to monitor gluten intake and compliment clinical methods to evaluate compliance to gluten‐free diet (GFD). In the present study, recent gluten intake was measured by GIP in children with coeliac disease (CD) and compared to routine clinical measures to evaluate GFD compliance.

Methods:

GIP was measured in 90 samples from 63 CD children (44 previously and 19 newly diagnosed with follow‐up samples at 6 and 12 months on GFD). Compliance to GFD was evaluated based on clinical assessment, tissue transglutaminase (tTG) levels, and Biagi score.

Results:

GIP was detectable in 16% of patients with previous CD diagnosis on GFD. Body mass index z score (P = 0.774), height z score (P = 0.723), haemoglobin concentration (P = 0.233), age (P = 0.448), sex (P = 0.734), or disease duration (P = 0.488) did not differ between those with detectable and nondetectable GIP. In newly diagnosed patients, on gluten‐containing diet, GIP was detectable in 95% of them. Following GFD initiation, GIP decreased (P < 0.001); 17% and 27% had detectable levels at 6 and 12 months, respectively. Compared to GIP, the Biagi score, tTG, and clinical assessment presented sensitivity of 17%, 42%, and 17%, respectively. Likewise, GIP was detectable in 16%, 16%, and 14% of patients evaluated as GFD compliant according to the Biagi score, tTG, and clinical assessment, respectively. A combination of methods did not improve identification of patients who were noncompliant.

Conclusions:

Inclusion of faecal GIP measurements is likely to improve identification of GFD recent noncompliance in CD management and could be incorporated into current follow‐up strategies.
Female Sex is Associated With Poor Health-related Quality of Life in Children at 12 Months Post-Hematopoietic Cell Transplantation
Authors: Bhatt Neel S. , Brazauskas Ruta , Tecca Heather R. , Vogel Jenny , Mattila Deborah , Lee Stephanie J. , Horowitz Mary M. , Rizzo J. Douglas , Shaw Bronwen E.
Published: June 2018

To study the factors associated with poorer health-related quality of life at 1-year post-allogeneic hematopoietic cell transplantation (alloHCT), a secondary analysis of a prospective feasibility study was performed. Pediatric Quality of Life Inventory questionnaires were collected in 76 children undergoing alloHCT at baseline (within 30 d before transplantation), day 100, 6 months, and 12 months posttransplantation. The global score improved post-HCT (baseline: 67.1, 12 mo: 76.6). Females (odds ratio, 6.5; 95% confidence interval, 1.002-42.17; P=0.04) and patients with low baseline scores (odds ratio, 7.2; 95% confidence interval, 1.07-48.63; P=0.04) had lower scores at 12 months post-HCT and suggest a target group for early interventions such as physical exercise, stress management, and cognitive behavior therapy.
Interruptions During Senior Nurse Handover in the Intensive Care Unit
Authors: Spooner Amy J. , Chaboyer Wendy , Aitken Leanne M.
Published: June 2018

Background:

Interruptions during handover may compromise continuity of care and patient safety.

Local Problem:

Interruptions occur frequently during handovers in the intensive care unit.

Methods:

A quality improvement study was undertaken to improve nursing team leader handover processes. The frequency, source, and reason interruptions occurred were recorded before and after a handover intervention.

Interventions:

The intervention involved relocating handover from the desk to bedside and using a printed version of an evidence-based electronic minimum data set. These strategies were supported by education, champions, reminders, and audit and feedback.

Results:

Forty handovers were audiotaped before, and 49 were observed 3 months following the intervention. Sixty-four interruptions occurred before and 52 after the intervention, but this difference was not statistically significant. Team leaders were frequently interrupted by nurses discussing personal or work-specific matters before and after the intervention.

Conclusions:

Further work is required to reduce interruptions that do not benefit patient care.
Spontaneous Pneumomediastinum in Connective Tissue Diseases
Authors: De Giacomi Federica , Baqir Misbah , Cox Christian W. , Moua Teng , Matteson Eric L. , Ryu Jay H.
Published: June 2018

Background

Spontaneous pneumomediastinum (SP) is an uncommon disorder but has been described in cases with connective tissue diseases (CTDs), most commonly dermatomyositis and polymyositis. We aimed to explore this relationship by analyzing the characteristics of CTD patients with SP.

Methods

Using a computer-assisted search, we identified 25 patients with CTD and SP evaluated between January 1997 and December 2016 at our institution. Clinicoradiologic characteristics, treatment, and outcomes were extracted and chest computed tomography studies analyzed.

Results

We identified 25 patients with CTD and SP. Median (range) age at SP occurrence was 55 (18–82) years, and 60% of the patients were women. Smoking history was present in 37%. Spontaneous pneumomediastinum was symptomatic in 56% of patients. Eighteen patients (72%) had a known CTD diagnosis, and 20 patients (80%) manifested radiologic evidence of interstitial lung disease. Spontaneous pneumomediastinum diagnosis was achieved with chest radiography in 20% of cases and chest computed tomography in the other cases. Spontaneous pneumomediastinum was managed with expectant observation alone in 22 cases (88%). Four patients (16%) had concomitant pneumothorax, 1 of whom required chest tube drainage. There were no deaths attributable to SP during the median (range) follow-up of 13 (0–174) months. Cumulative survival was 52% at 1 year and 40% at 2 years.

Conclusions

Spontaneous pneumomediastinum is an uncommon manifestation of CTD and usually occurs in the presence of interstitial lung disease. Although SP seems to be associated with a relatively benign short-term course, occurrence of SP in CTD patients may be a poor prognostic factor.
Pediatric 131I-MIBG Therapy for Neuroblastoma
Authors: Willegaignon José , Crema Karin Paola , Oliveira Nathaliê Canhameiro , Pelissoni Rogério Alexandre , Coura-Filho George Barberio , Sapienza Marcelo Tatit , Buchpiguel Carlos Alberto
Published: June 2018

Purpose

131I-metaiodobenzylguanidine (131I-MIBG) has been used in the diagnosis and therapy of neuroblastoma in adult and pediatric patients for many years. In this study, we evaluated whole-body 131I-MIBG clearance and radiation doses received by patients, family caregivers, and medical staff to establish appropriate radiation safety measures to be used in therapy applications.

Methods

Research was focused on 23 children and adolescents with metastatic neuroblastoma, with ages ranging from 1.8 to 13 years, being treated with 131I-MIBG. Based on measured external dose rates from patients, dosimetric data to patients, family members, and others were calculated.

Results

The mean ± SD 131I-MIBG activity administered was 8.55 ± 1.69 GBq. Percent whole-body retention rates of 131I-MIBG at 24, 48, and 72 hours after administration were 48% ± 7%, 23% ± 7%, and 12% ± 6%, with a whole-body 131I-MIBG effective half-life of 23 ± 5 hours for all patients. The mean doses for patients were 0.234 ± 0.096 mGy·MBq−1 to red-marrow and 0.251 ± 0.101 mGy·MBq−1 to whole body. The maximum potential radiation doses transmitted by patients to others at 1.0 m was estimated to be 11.9 ± 3.4 mSv, with 97% of this dose occurring over 120 hours after therapy administration. Measured mean dose received by the 22 family caregivers was 1.88 ± 1.85 mSv, and that received by the 19 pediatric physicians was 43 ± 51 μSv.

Conclusion

In this study, we evaluated the whole-body clearance of 131I-MIBG in 23 pediatric patients, and the radiation doses received by family caregivers and medical staff during these therapy procedures, thus facilitating the establishment of radiation safety measures to be applied in pediatric therapy.
Uterine Corpus Metastasis From Rectal Adenocarcinoma Detected Using 18F-FDG PET/CT
Authors: Wang Hongxi , Su Minggang , Cui Futao , Wu Xia , Tian Rong
Published: June 2018

We report an unusual case of uterine corpus metastasis from rectal adenocarcinoma detected using 18F-FDG PET/CT. A 47-year-old woman was diagnosed with rectal adenocarcinoma and treated with surgery and radiochemotherapy 3 years ago. During follow-up, she presented with lower abdomen pain and elevated tumor markers, but ultrasonography findings were unremarkable. We performed an 18F-FDG PET/CT scan, which showed intense 18F-FDG avidity in the myometrium of the uterine corpus. Uterine corpus metastasis was suspected, and complementary MRI and diagnostic curettage histopathology confirmed uterine metastasis from rectal adenocarcinoma.
68Ga-PSMA PET/CT in Patients With Biochemical Recurrence of Prostate Cancer
Authors: Zacho Helle D. , Nielsen Julie B. , Dettmann Katja , Haberkorn Uwe , Langkilde Niels C. , Jensen Jørgen B. , Petersen Lars J.
Published: June 2018

Purpose of the Report

The aim of this study was to prospectively investigate the detection rate of 68Ga-PSMA PET/CT in biochemical recurrence (BCR) of prostate cancer and its impact on patient management.

Materials and Methods

Patients with BCR after curatively intended treatment of prostate cancer were included. Each patient underwent a 68Ga-PSMA PET/CT. Changes in patient management based on the results of 68Ga-PSMA PET/CT were assessed.

Results

Seventy patients were included. Sixty-four patients (91%) had radical prostatectomy, of whom 17 patients (24%) received salvage radiation therapy due to first biochemical relapse. Six patients (9%) underwent radiation therapy as the primary treatment. 68Ga-PSMA PET/CT detected recurrent disease in 37 patients (53%). The detection rate was 22% for prostate-specific antigen (PSA) levels up to 0.5 ng/mL compared with 83% for PSA levels greater than 0.5 ng/mL. Pathological uptake of 68Ga-PSMA was observed in 4 (16%) of 21, 4 (44%) of 9, 0 of 1, 7 (70%) of 10, and 22 (88%) of 25 patients with PSA levels from 0.2 to 0.3 ng/mL, 0.31 to 0.4 ng/mL, 0.41 to 0.5 ng/mL, 0.51 to 1 ng/mL, and greater than 1 ng/mL, respectively. Prostate-specific antigen was significantly higher in PSMA-positive patients than in PSMA-negative patients. In 15 (22%) of 69 patients, the results caused a definite change in patient management, and in another 15 (22%) of 69 patients, 68Ga-PSMA PET/CT guided the choice of treatment.

Conclusions

68Ga-PSMA PET/CT detects lesions in a large proportion of patients with BCR. Detection rates at low PSA levels (<0.5 ng/mL) were notably below the values reported in previous retrospective studies; however, detection rates improved with increasing PSA levels.
Factors That Affect Medical Students' Perception and Impression of a Plastic Surgery Program
Authors: Zuo Kevin J. , Retrouvey Helene , Wanzel Kyle R.
Published: June 2018

Objective

Securing a residency training position in plastic surgery is highly competitive each year with a limited quota of positions and numerous qualified applicants. Although previous studies have highlighted the importance of residency programs and applicants seeking a “good fit,” it remains poorly understood what influences a medical student's impression and desire to train at a certain program over others. The objective of this cross-sectional study was to identify which specific potentially modifiable factors during elective rotations and program interviews were most important to Canadian medical students when ranking plastic surgery programs.

Methods

An electronic survey with 42 questions was administered to Canadian final year medical students who applied through the 2017 Canadian Residency Match Service to the plastic surgery training program at the University of Toronto. The survey consisted of 7-point Likert scale questions related to demographics, general factors affecting impression of a plastic surgery program, and specific factors related to the elective and interview experiences. Survey responses were collected anonymously for analysis.

Results

Twenty-three of 46 applicants completed the survey (50% response rate). The most important general factors affecting a medical student's impression and desire to train at a residency program were mentors at a specific program (weighted average, 6.39) and geographic location of a program (weighted average, 5.65). During elective rotations, the most important factors identified were overall impression of resident and staff collegiality (weighted average, 6.57), overall impression of resident happiness (weighted average, 6.52), and having a formal rotation-end debrief evaluation with the supervising staff (weighted average, 6.04). At program interviews, perceiving an atmosphere of collegiality (weighted average, 6.45) and opportunities to interact with residents and faculty at an organized social event (weighted average, 5.95) were considered of greatest importance.

Conclusions

Current applicants to plastic surgery in Canada prioritize resident happiness, program collegiality, and meaningful faculty relationships, such as those with a mentor, when ranking residency programs. Although finding a mutually “good fit” between applicant and program will remain a major aim, these findings indicate the importance of certain tangible, potentially modifiable factors that affect how medical students ultimately perceive and rank plastic surgery programs.
The Practice of Overlapping Colorectal Operations in a Tertiary Care Center Is Safe
Authors: Shogan Benjamin D. , Harmsen William S. , Dozois Eric J. , Nelson Heidi , Larson David W.
Published: June 2018

Objective:

Determine the safety of overlapping surgery in a tertiary care colorectal surgery practice.

Although overlapping surgery is common in academic centers, reports on outcomes of this practice are limited. The primary aim of this study was to investigate the safety of overlapping surgery in a dedicated tertiary care academic colorectal practice by comparing groups of patients who did or did not have their surgery performed in an overlapping fashion.

Methods:

Retrospective review of 1270 colorectal patients undergoing inpatient colorectal surgery at our institution. Eligible participants were all patients undergoing elective inpatient colorectal surgery by one of the colorectal surgeons at the Mayo Clinic Rochester between January 1, 2012 and December 31, 2015. Patients under the age of 18 or who underwent an emergent procedure were excluded. Data were abstracted using the American College of Surgeons National Quality Improvement Program (ACS-NSQIP) database. Additionally, each subject's chart was reviewed and further abstracted. The safety of overlapping surgery on outcomes was assessed using multiple multivariable models.

Results:

One thousand two hundred seventy patients were included in the study cohort of whom 50.7% were female and the average age was 55.4 years. Overlapping surgery occurred in 576 patients (45%). There were no significant differences in demographic, surgical indications, procedures, or operative complexity between patients undergoing overlapping surgery and those who did not. Overall adverse events were significantly less likely in patients undergoing overlapping surgery compared with those who did not (18.4% vs 23.6%, P = 0.02). We found that overlapping surgery was associated with significantly less adverse events compared with patients not undergoing overlapping surgery using a model that controlled for the effect of the individual surgeon (OR 0.7, 95% CI 0.6 – 0.96; P = .02) and a multivariable propensity score (OR 0.7, 95% CI 0.5– 0.9; P = 01).

Conclusions:

Overlapping surgery in a tertiary care colorectal practice is safe and not associated with adverse patient outcomes.
Towards a framework for reporting self-guided interventions for people with cancer
Authors: Ugalde Anna , Kiss Nicole , Livingston Patricia , Aranda Sanchia
Published: June 2018

Purpose of review

The purpose of this article is to provide an updated review exploring the recent developments in the field of self-guided interventions and describe the state of knowledge. This article builds on a previous systematic review on self-guided interventions, finding that the recent literature demonstrates that evidence for these interventions is mixed. The field is limited by descriptions of these interventions, and it is not possible to ascertain what aspects of interventions are more successful.

Recent findings

Development of a reporting framework whereby self-guided interventions could be clearly presented, would be a substantial contribution to understanding the evidence for these studies. Recent findings also support the need to understand patient adherence and engagement, which could be achieved within a reporting framework. Additionally, ensuring patient safety is paramount and all studies should develop strategies to ensure patients can engage with these studies in a way that allows them to access more help and support if required.

Self-guided interventions have potential for implementation and further translation because of being cost-effective and requiring few resources; and a reporting framework has the capacity to lead to clearer definitions and descriptions; and significantly improve the quality of evidence for these studies.
Impact of the Current Versus the Previous Diagnostic Threshold on the Outcome of Patients With Borderline Changes Suspicious for T Cell–mediated Rejection Diagnosed on Indication Biopsies
Authors: McRae Michael , Bouchard-Boivin François , Béland Stéphanie , Noël Réal , Côté Isabelle , Lapointe Isabelle , Lesage Julie , Latulippe Eva , Riopel Julie , Santoriello Dominick , Husain Syed A. , Désy Olivier , Houde Isabelle , Batal Ibrahim , De Serres Sacha A.
Published: June 2018

Background

Since the borderline changes suspicious for acute T cell–mediated rejection (BL) category was broadened, there has been a debate regarding the right threshold for tubulitis and interstitial inflammation scores.

Methods

We studied a first cohort of 111 patients with BL found on an indication biopsy between 2006 and 2016 and compared those with scores of t1i0 (BLt1i0) to those with higher scores (BL≥t1i1). A second cohort of 56 patients with BL was used for external validation. We used a composite endpoint of death-censored graft failure or doubling of the serum creatinine level postbiopsy.

Results

In the first cohort, 68% (75/111) of the BL cases fell in the BLt1i0 group. At 5 years, the occurrence of the composite endpoint was 5% and 14% for BLt1i0 and BL≥t1i1, respectively. In contrast, the endpoint occurred in 5% of nonrejectors and 21% of patients with T cell–mediated rejection. In the validation cohort, 8% versus 36% of BLt1i0 and BL≥t1i1 reached the endpoint, respectively. Multivariable Cox modeling revealed that BLt1i0 patients had a prognosis similar to that of nonrejectors (adjusted hazard ratio, 0.6; 95% confidence interval, 0.1-2.2; P = 0.40) but better than that of patients with BL≥t1i1 (hazard ratio, 3.8; 95% confidence interval, 1.3-11.5; P = 0.02). Sensitivity analyses restricted to death-censored graft loss or using time posttransplant as the time of reference provided similar results.

Conclusions

In summary, patients with BLt1i0 have a different prognosis to that of BL≥t1i1 patients, which brings into question the current diagnostic thresholds.
Small Molecule Tyrosine Kinase Inhibitor Nintedanib Reduces Development of Cardiac Allograft Vasculopathy in Murine Aortic Allografts
Authors: Gocht Annika , Spriewald Bernd , Distler Jörg H.W. , Ramsperger-Gleixner Martina , Ensminger Stephan M. , Weyand Michael , Heim Christian
Published: June 2018

Background

Nintedanib is a small molecule tyrosine kinase inhibitor that blocks the action of the platelet-derived growth factor receptor (PDGFR), the vascular endothelial growth factor receptor (VEGFR) and the fibroblast growth factor receptor. All of these receptors have been shown to be involved in the development of cardiac allograft vasculopathy (CAV) after heart transplantation. We therefore hypothesized that blocking these tyrosine kinase receptors with nintedanib could prevent CAV.

Methods

CBA/JRj (H2k) mice underwent an abdominal aortic transplantation with a graft derived from fully allogeneic C57BL/6JRj (H2b) mice. Nintedanib was given daily from the first day after transplantation until harvest on day 14 for polymerase chain reaction analysis of intragraft cytokine expression or harvest on day 30 for histological analysis of the graft.

Results

Nintedanib treatment resulted in significantly reduced neointima formation in the aortic graft compared with untreated control allografts. Interestingly, the immigration of smooth muscle cells into the neointima was markedly reduced while graft infiltrating macrophages and T cells were not altered in nintedanib-treated animals. The expression of the growth factor PDGF was significantly reduced in the nintedanib group going along with a distinctly reduced expression of the corresponding receptors PDGFR α and -β.

Conclusions

Treatment with nintedanib caused a significant reduction of CAV development after aortic transplantation in mice. We hypothesize the attenuated neointima formation in nintedanib-treated animals to be mediated by a direct inhibition of intimal smooth muscle cell proliferation via reduced expression of PDGF and the appropriate receptors PDGFR α + β.
Development of white matter fibre density and morphology over childhood: a longitudinal fixel-based analysis
Authors: Genc Sila , Smith Robert E , Malpas Charles B , Anderson Vicki , Nicholson Jan M , Efron Daryl , Sciberras Emma , Seal Marc L , Silk Timothy J
Published: June 2018

Purpose

White matter fibre development in childhood involves dynamic changes to microstructural organisation driven by increasing axon diameter, density, and myelination. However, there is a lack of longitudinal studies that have quantified advanced diffusion metrics to identify regions of accelerated fibre maturation, particularly across the early pubertal period. We applied a novel longitudinal fixel-based analysis (FBA) framework, in order to estimate microscopic and macroscopic white matter changes over time.

Methods

Diffusion-weighted imaging (DWI) data were acquired for 59 typically developing children (27 female) aged 9 – 13 years at two time-points approximately 16 months apart (time-point 1: 10.4 ± 0.4 years, time-point 2: 11.7 ± 0.5 years). Whole brain FBA was performed using the connectivity-based fixel enhancement method, to assess longitudinal changes in fibre microscopic density and macroscopic morphological measures, and how these changes are affected by sex, pubertal stage, and pubertal progression. Follow-up analyses were performed in sub-regions of the corpus callosum to confirm the main findings using a Bayesian repeated measures approach.

Results

There was a statistically significant increase in fibre density over time localised to medial and posterior commissural and association fibres, including the forceps major and bilateral superior longitudinal fasciculus. Increases in fibre cross-section were substantially more widespread. The rate of fibre development was not associated with age or sex. In addition, there was no significant relationship between pubertal stage or progression and longitudinal fibre development over time. Follow-up Bayesian analyses were performed to confirm the findings, which supported the null effect of the longitudinal pubertal comparison.

Conclusion

Using a novel longitudinal fixel-based analysis framework, we demonstrate that white matter fibre density and fibre cross-section increased within a 16-month scan rescan period in specific regions. The observed increases might reflect increasing axonal diameter or axon count. Pubertal stage or progression did not influence the rate of fibre development in the early stages of puberty. Future work should focus on quantifying these measures across a wider age range to capture the full spectrum of fibre development across the pubertal period.
Empowering conservation practice with efficient and economical genotyping from poor quality samples
Authors: Natesh Meghana , Taylor Ryan W. , Truelove Nathan , Hadly Elizabeth A. , Palumbi Stephen , Petrov Dmitri , Ramakrishnan Uma
Published: June 2018

Moderate to high density genotyping (100+ SNPs) is widely used to determine and measure individual identity, relatedness, fitness, population structure and migration in wild populations.

However, these important tools are difficult to apply when high-quality genetic material is unavailable. Most genomic tools are developed for high quality DNA sources from labor medical settings. As a result, most genetic data from market or field settings is limited to easily amplified mitochondrial DNA or a few microsatellites.

To enable genotyping in conservation contexts, we used next-generation sequencing of multiplex PCR products from very low-quality DNA extracted from feces, hair, and cooked samples. We demonstrated utility and wide-ranging potential application in endangered wild tigers and tracking commercial trade in Caribbean queen conch.

We genotyped 100 SNPs from degraded tiger samples to identify individuals, discern close relatives, and detect population differentiation. Co-occurring carnivores do not amplify (e.g. Indian wild dog/Dhole) or are monomorphic (e.g. leopard). 62 SNPs from conch fritters and field-collected samples were used to test relatedness and detect population structure.

We provide proof-of-concept for a rapid, simple, cost-effective, and scalable method (for both samples and number of loci), a framework that can be applied to other conservation scenarios previously limited by low quality DNA samples. These approaches provide a critical advance for wildlife monitoring and forensics, open the door to field-ready testing, and will strengthen the use of science in policy decisions and wildlife trade.
Hydroxytyrosol (HT) analogues act as potent antifungals by direct disruption of the fungal cell membrane
Authors: Diallinas George , Rafailidou Nausica , Kalpaktsi Ioanna , Christina Komianou Aikaterini , Tsouvali Vivian , Zantza Iliana , Mikros Emmnauel , Leandros Skaltsounis Alexios , Kostakis Ioannis K.
Published: June 2018

Fungal infections constitute an emerging threat and a prevalent health problem due to increasing number of immunocompromised people and pharmacological or other treatments aiming at viral infections, cancer or allergies. Currently used antifungals suffer from inefficiency, toxic side effects and developing drug-resistance. Additionally, over the last two decades no new classes of antifungals have been approved, emphasizing the urgent need for developing a novel generation of antifungals. Here we investigate the antifungal activity of a series of chemically synthesized Hydroxytyrosol (HT) analogues. HT is one of the major phenolic compounds in olive oil, shown to possess radical-scavenging antioxidant, antiproliferative, proapoptotic and anti-inflammatory activities. No previous report has studied HT analogues as antifungals. We show that specific analogues have broad and strong antifungal activity, significantly stronger than the parent compound HT. Using A. nidulans as an in vivo cellular model system, we show that antifungal HT analogues have an unprecedented efficiency in fungal plasma membrane destruction. Importantly, antifungal HT analogues did not show toxicity in a mammalian cell line, whereas no resistance to HT analogues was obtained by standard mutagenesis. Our results open the way for the development of a novel, efficient and safer class of antifungals.
A high-quality grapevine downy mildew genome assembly reveals rapidly evolving and lineage-specific putative host adaptation genes
Authors: Dussert Yann , Mazet Isabelle D. , Couture Carole , Gouzy Jérôme , Piron Marie-Christine , Kuchly Claire , Bouchez Olivier , Rispe Claude , Mestre Pere , Delmotte François
Published: June 2018

Downy mildews are obligate biotrophic oomycete pathogens that cause devastating plant diseases on economically important crops. Plasmopara viticola is the causal agent of grapevine downy mildew, a major disease in vineyards worldwide. We sequenced the genome of Pl. viticola with PacBio long reads and obtained a new 92.94 Mb assembly with high continuity (359 scaffolds for a N50 of 706.5 kb) due to a better resolution of repeat regions. This assembly presented a high level of gene completeness, recovering 1,592 genes encoding secreted proteins involved in plant-pathogen interactions. Pl. viticola had a two-speed genome architecture, with secreted protein-encoding genes preferentially located in gene-sparse, repeat-rich regions and evolving rapidly, as indicated by pairwise dN/dS values. We also used short reads to assemble the genome of Plasmopara muralis, a closely related species infecting grape ivy (Parthenocissus tricuspidata). The lineage-specific proteins identified by comparative genomics analysis included a large proportion of RxLR cytoplasmic effectors and, more generally, genes with high dN/dS values. We identified 270 candidate genes under positive selection, including several genes encoding transporters and components of the RNA machinery potentially involved in host specialization. Finally, the Pl. viticola genome assembly generated here will allow the development of robust population genomics approaches for investigating the mechanisms involved in adaptation to biotic and abiotic selective pressures in this species.

DATA AVAILABILITY

Raw reads and genome assemblies have been deposited in GenBank (BioProjects PRJNA329579 for Pl. viticola and PRJNA448661 for Pl. muralis). Genome assemblies, gene annotations and analysis files (e.g. orthology relationships, full tables for GO enrichment analyses, pairwise dN/dS values and branch-site tests) have been deposited in Dataverse (Pl. viticola assembly and annotation: doi.org/10.15454/4NYHD6, Pl. muralis assembly and annotation: doi.org/10.15454/Q1QJYK, analysis files: doi.org/10.15454/8NZ8X9). Links to the data and information about the grapevine downy mildew genome project can be found at http://grapevine-downy-mildew-genome.com/.
Mutations in Kinesin Family Member 6 Reveal Specific Role in Ependymal Cell Function and Human Neuro-Cranial Development
Authors: Konjikusic Mia J. , Yeetong Patra , Ittiwut Rungnapa , Suphapeetiporn Kanya , Wallingford John B. , Gurnett Christina A. , Shotelersuk Vorasuk , Gray Ryan S.
Published: June 2018

Cerebrospinal fluid flow is crucial for neurodevelopment and homeostasis of the ventricular system of the brain, with localized flow being established by the polarized beating of the ependymal cell (EC) cilia. Here, we report a homozygous one base-pair deletion, c.1193delT (p.Leu398Glnfs*2), in the Kinesin Family Member 6 (KIF6) gene in a child displaying neurocranial defects and intellectual disability. To test the pathogenicity of this novel human KIF6 mutation we engineered an analogous C-terminal truncating mutation in mouse. These mutant mice display severe, postnatal-onset hydrocephalus. We generated a Kif6-LacZ transgenic mouse strain and report expression specifically and uniquely within the ependymal cell (EC) layer of the brain, without labeling other multiciliated mouse tissues. Analysis of Kif6 mutant mice with scanning electron microscopy (SEM) and immunofluorescence (IF) revealed a reduction in EC cilia, without effect on other multiciliated tissues. Consistent with our findings in mice, defects of the ventricular system and EC cilia were observed in kif6 mutant zebrafish. Overall, this work describes the first clinically-defined KIF6 homozygous null mutation in human and defines KIF6 as a conserved mediator of neuro-cranial morphogenesis with a specific role in the maintenance of EC cilia in vertebrates.

AUTHOR SUMMARY

Cerebrospinal fluid flow is crucial for neurodevelopment and homeostasis of the ventricular system of the brain. Localized flows of cerebrospinal fluid throughout the ventricular system of the brain are established from the polarized beating of the ependymal cell (EC) cilia. Here, we identified a homozygous truncating mutation in KIF6 in a child displaying neuro-cranial defects and intellectual disability. To test the function of KIF6 in vivo, we engineered mutations of Kif6 in mouse. These Kif6 mutant mice display severe hydrocephalus, coupled with a loss of EC cilia. Similarly, we observed hydrocephalus and a reduction in EC cilia in kif6 mutant zebrafish. Overall, this work describes the first clinically-defined KIF6 mutation in human, while our animal studies demonstrate the pathogenicity of mutations in KIF6 and establish KIF6 as a conserved mediator of neuro-cranial development and EC cilia maintenance in vertebrates.
Free-living Bacterial Communities Are Mostly Dominated by Oligotrophs
Authors: Gao Yingnan , Wu Martin
Published: June 2018

In response to resource availability, bacteria have evolved two distinct ecological strategies. Copiotrophic bacteria grow fast and are heavily favored by selection where the resource is abundant. In contrast, oligotrophic bacteria grow slowly but more efficiently and are highly adaptive in nutrient-poor environments (Koch, 2001). Although oligotrophs and copiotrophs are ubiquitous, except for a few well-characterized environments like the open ocean and animal gut, the relative abundance of oligotrophic and copiotrophic bacteria and their importance in the global ecosystem are still unclear. In addition, although several studies have demonstrated the impact of nutrient availability on the bacterial community structure under experimental conditions (Klappenbach et al., 2000, Nemergut et al., 2016), the role of nutrients in shaping the structures of bacterial communities in their natural habitats remains largely unknown. Using the ribosomal RNA operon (rrn) copy number to capture the bacterial ecological strategy, we analyzed 44,045 samples from two large bacterial community repositories that cover 78 environmental types. Here we show that animal-associated microbiota are dominated by copiotrophs while plant-associated and free-living bacterial communities are mostly dominated by oligotrophs. Our results suggest that nutrient availability plays an important role in determining the structure and ecological strategy of bacterial communities in nature. We demonstrate that the average and distribution of rrn copy number are simple yet robust predictors of the ecological strategy of bacterial communities that can be applied to all sequence-based microbial surveys to link the community structure and function.