bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Corneal Neovascularization Using Optical Coherence Tomography Angiography in Patients With Limbal Stem Cell Deficiency
Authors: Oie Yoshinori , Nishida Kohji
Published: September 2017

Purpose:

Detection of the exact area of corneal neovascularization using slit-lamp photography is often difficult. Thus, we evaluated corneal neovascularization in patients with limbal stem cell deficiency using optical coherence tomography angiography (OCTA).

Methods:

Five patients with 5 eyes showing partial or total limbal stem cell deficiency were enrolled. Three eyes had severe corneal scarring. Five 6- × 6-mm images (frontal, upper, lower, nasal, and temporal) were obtained by OCTA. Slit-lamp photography was performed for all patients on the same day.

Results:

OCTA has 2 advantages over slit-lamp photography for clear demonstration of corneal neovascularization. First, OCTA can show neovascularization in cases with severe corneal opacification. Second, OCTA can detect not only large vessels but also small vessels that cannot be seen by slit-lamp photography.

Conclusions:

OCTA is a powerful tool for objective evaluation of vascularization in the anterior and posterior segments of the eye. We have demonstrated that OCTA can visualize corneal neovascularization in patients with corneal diseases more clearly than slit-lamp photography.
Life-Threatening Massive Hemoptysis After Cryoablation for Atrial Fibrillation
Authors: Jayaschandran Vivek , Mertens Amy N. , Patel Vishal K. , Dalal Bhavinkumar
Published: September 2017

A 59-year-old man developed massive hemoptysis, 1 month after undergoing cryoablation procedure for atrial fibrillation. He underwent emergent bronchoscopy that revealed massive, active bleeding with clots requiring repeated suctioning, epinephrine, and cold saline injection. The source of bleeding was identified in a follow-up bronchoscopy performed few days later—a 2×3 cm area of ulceration of the left main stem bronchus which was missed in the initial bronchoscopy owing to blood obscuring the field of vision. Considering the timeline, the ulcer most likely resulted from cryoablation-induced bronchial injury. Patient remained asymptomatic after stabilization and 2 months following discharge, another bronchoscopy was performed which showed the ulcer to be healing. Hemoptysis following cryoablation is quite rare with a reported incidence <2%. The cases of hemoptysis reported thus far have all been mild and self-limiting and manifesting within hours to days following the procedure. To our knowledge, this is the first reported case of massive hemoptysis associated with cryoballoon ablation, presenting 1 month after procedure.
Clinical Success Stenting Distal Bronchi for “Lobar Salvage” in Bronchial Stenosis
Authors: Sethi Sonali , Gildea Thomas R. , Almeida Francisco A. , Cicenia Joseph C. , Machuzak Michael S.
Published: September 2017

Background:

Airway stents are traditionally used in central airway obstructions to maintain airway patency. Historically, distal bronchial stenting within lobar and segmental bronchi has not been amenable to stenting. In addition, there are questionable benefits to stenting small airways. The Atrium iCast stent is a polytetrafluoroethylene covered stainless steel balloon deployed stent which can be deployed through a flexible bronchoscope under direct visualization. The purpose of this study was to assess the feasibility, complications, and long-term impact of using this stent in patients with lobar bronchial stenosis either secondary to malignancy or benign etiologies.

Methods:

All records of patients who had the placement of an iCast stent were reviewed over 3.5 years. For each patient the age, sex, location, histology, stent size, duration of stent placement, radiographic improvement, and complications were collected.

Results:

A total of 122 iCast stents were deployed in 38 patients with lobar bronchial stenosis. The average age was 58 years with 50% male. The etiology included 45% malignant and 55% due to benign conditions. In total, 18.5% patients had stents placed in >1 segment. There was an average of 4 procedures per patient with a mean time to stent revision or removal of 85 days. All patients had symptomatic or radiographic improvement. Common complications included migration (10%), granulation tissue formation (5%), deployment malfunction (2%), stent dislodgement immediately after deployment (2%), mucous plugging (1%), and tumor occlusion (1%).

Conclusion:

Stenting small airways with lobar salvage is feasible and improves symptoms and radiographic outcomes.
Vitamin D in obesity
Authors: Walsh Jennifer S. , Bowles Simon , Evans Amy L.
Published: September 2017

Purpose of review

Vitamin D is essential for bone health, and may also have important functions in immunity and other systems. Vitamin D deficiency is common, and testing and supplementation is increasing. Serum vitamin D is lower in obese people; it is important to understand the mechanism of this effect and whether it indicates clinically significant deficiency.

Recent findings

Vitamin D is fat soluble, and distributed into fat, muscle, liver, and serum. All of these compartments are increased in volume in obesity, so the lower vitamin D likely reflects a volumetric dilution effect and whole body stores of vitamin D may be adequate. Despite lower serum vitamin D, obese adults do not have higher bone turnover or lower bone mineral density. Patients undergoing bariatric surgery do have bone loss, and ensuring vitamin D sufficiency in these patients may help to attenuate bone loss.

Lower vitamin D in obese people is a consistent finding across age, ethnicity, and geography. This may not always reflect a clinical problem. Obese people need higher loading doses of vitamin D to achieve the same serum 25-hydroxyvitamin D as normal weight.
Do prehospital providers and emergency nurses agree on triage assignment?: an efficacy study
Authors: Skjøt-Arkil Helene , Pontoppidan Louise L. , Laursen Jens O. , Giebner Matthias , Andersen Jesper D. , Mogensen Christian B.
Published: September 2017

Objectives

The aim of this study was to investigate the agreement on triage level between prehospital providers and emergency department (ED) nurses in clinical practice when using the same triage system. The objectives were as follows: (a) What is the agreement of triage between prehospital providers and ED nurses, when using Danish Emergency Process Triage (DEPT) correctly? (b) Which part of the triage process yields the highest agreement regarding the final triage?

Methods

The study was a prospective and observational efficacy study. Patients transported to the ED by ambulances were included. They were triaged by prehospital providers while being transported by ambulance to the ED, and by ED nurses upon arrival. Triage was done using the DEPT – a five-level triage system based on vital signs and a presenting complaint algorithm. An agreement analysis was performed.

Results

DEPT was used correctly by both professions in 292 patients. In 182 (62%) patients the prehospital providers and the ED nurses agreed on the same triage level. This equals toκ=0.47 [95% confidence interval (CI): 0.41–0.56]. When considering the triage based on vital signs the agreement was 72% (κ=0.46; 95% CI: 0.41–0.47), and based on presenting complaint the agreement was 46% (κ=0.41; 95% CI: 0.37–0.44).

Conclusion

There was a moderate interrater agreement on triage assignment between ED nurses and prehospital providers. They agreed on final triage more often if they agreed on triage based on vital signs rather than presenting complaints.
Trajectories of Glycemic Change in a National Cohort of Adults With Previously Controlled Type 2 Diabetes
Authors: McCoy Rozalina G. , Ngufor Che , Van Houten Holly K. , Caffo Brian , Shah Nilay D.
Published: September 2017

Background:

Individualized diabetes management would benefit from prospectively identifying well-controlled patients at risk of losing glycemic control.

Objectives:

To identify patterns of hemoglobin A1c (HbA1c) change among patients with stable controlled diabetes.

Research Design:

Cohort study using OptumLabs Data Warehouse, 2001–2013. We develop and apply a machine learning framework that uses a Bayesian estimation of the mixture of generalized linear mixed effect models to discover glycemic trajectories, and a random forest feature contribution method to identify patient characteristics predictive of their future glycemic trajectories.

Subjects:

The study cohort consisted of 27,005 US adults with type 2 diabetes, age 18 years and older, and stable index HbA1c <7.0%.

Measures:

HbA1c values during 24 months of observation.

Results:

We compared models with k=1, 2, 3, 4, 5 trajectories and baseline variables including patient age, sex, race/ethnicity, comorbidities, medications, and HbA1c. The k=3 model had the best fit, reflecting 3 distinct trajectories of glycemic change: (T1) rapidly deteriorating HbA1c among 302 (1.1%) youngest (mean, 55.2 y) patients with lowest mean baseline HbA1c, 6.05%; (T2) gradually deteriorating HbA1c among 902 (3.3%) patients (mean, 56.5 y) with highest mean baseline HbA1c, 6.53%; and (T3) stable glycemic control among 25,800 (95.5%) oldest (mean, 58.5 y) patients with mean baseline HbA1c 6.21%. After 24 months, HbA1c rose to 8.75% in T1 and 8.40% in T2, but remained stable at 6.56% in T3.

Conclusions:

Patients with controlled type 2 diabetes follow 3 distinct trajectories of glycemic control. This novel application of advanced analytic methods can facilitate individualized and population diabetes care by proactively identifying high risk patients.
Tics and Tourette: a clinical, pathophysiological and etiological review
Authors: Dale Russell C.
Published: September 2017

Purpose of review

Describe developments in the etiological understanding of Tourette syndrome.

Recent findings

Tourette syndrome is a complex heterogenous clinical syndrome, which is not a unitary entity. Pathophysiological models describe gamma-aminobutyric acid-ergic-associated disinhibition of cortico-basal ganglia motor, sensory and limbic loops. MRI studies support basal ganglia volume loss, with additional white matter and cerebellar changes. Tourette syndrome cause likely involves multiple vulnerability genes and environmental factors. Only recently have some vulnerability gene findings been replicated, including histidine decarboxylase and neurexin 1, yet these rare variants only explain a small proportion of patients. Planned large genetic studies will improve genetic understanding. The role of inflammation as a contributor to disease expression is now supported by large epidemiological studies showing an association with maternal autoimmunity and childhood infection. Investigation of blood cytokines, blood mRNA and brain mRNA expression support the role of a persistent immune activation, and there are similarities with the immune literature of autistic spectrum disorder. Current treatment is symptomatic, although there is a better appreciation of factors that influence treatment response.

At present, therapeutics is focused on symptom-based treatments, yet with improved etiological understanding, we will move toward disease-modifying therapies in the future.
Dietary intervention for preventing food allergy in children
Authors: Wang Yichao , Allen Katrina J. , Koplin Jennifer J.
Published: September 2017

Purpose of review

In the past decade, food allergy has been increasingly recognized as an important public health issue. The role of maternal and infant diet in the development of food allergy has been a major focus of research throughout this period. Recently, research in this area has moved from observational studies to intervention trials, and the findings from these trials have started to influence infant feeding guidelines. In this article, we review recent studies of dietary interventions for preventing food allergy, summarize current knowledge and discuss future research directions.

Recent findings

The latest result from an intervention trial shows that introduction of peanut in the first year of life reduces the risk of peanut allergy in high-risk infants. A systematic review and meta-analysis of intervention trials also suggests a protective effect of egg introduction from around 4 to 6 months of age for reducing the risk of egg allergy, with most studies conducted in high-risk infants. Despite several intervention trials involving modifications to the maternal diet, the effect of maternal diet during pregnancy and lactation in preventing food allergy remains unclear.

Earlier introduction of allergenic foods is a promising intervention to reduce the risk of some food allergies in high-risk infants. Further work is needed to improve knowledge of how to prevent food allergy in the general population.
Quality Measures
Authors: Baernholdt Marianne , Dunton Nancy , Hughes Ronda G. , Stone Patricia W. , White Kathleen M.
Published: September 2017

For quality measures, confusion and discontentment have increased, as availability of electronic data and data collection tools has expanded. We examined current issues with quality measures across 4 stakeholder groups: developers, regulators/endorsers, data collectors, and consumer advocates. There are missing quality measures, issues with data quality and purpose, questionable usability of electronic health records, and an increased measurement burden and cost. Policymakers, administrators, health care professionals, and consumers need to collaborate on measure development and selection.
Validation of Fear of Falling and Balance Confidence Assessment Scales in Persons With Dystonia
Authors: Boyce Melani J. , Lam Lawrence , Chang Florence , Mahant Neil , Fung Victor S. C. , Bradnam Lynley
Published: September 2017

Background and Purpose:

Falls are problematic for people living with neurological disorders and a fear of falling can impact on actual falls. Fear of falling is commonly assessed using the Falls Self-Efficacy Scale International (FES-I) or the Activities-specific Balance Confidence (ABC) Scale. These scales can predict risk of falling. We aimed to validate the FES-I and the ABC in persons with dystonia.

Methods:

We conducted an online survey of people with dystonia, collecting information on demographics, 6-month falls history, dystonia disability, and the FES-I and ABC scales. Scales were validated for structural validity and internal consistency. We also examined goodness-of-fit, convergent validity, and predictive validity, and determined cutoff scores for predicting falls risk.

Results:

Survey responses (n = 122) showed that both FES-I and ABC scales have high internal validity and convergent validity with the Functional Disability Questionnaire in persons with dystonia. Each scale examines a single factor, fear of falling (FES-I) and balance confidence (ABC). At least one fall was reported by 39% of participants; the cutoff value for falls risk was found to be 29.5 and 71.3 for the FES-I and the ABC respectively.

Discussion and Conclusions:

The FES-I and the ABC scales are valid scales to examine fear of falling and balance confidence in persons with dystonia. Fear of falling is high and balance confidence is low and both are worse in those with dystonia who have previously fallen.

Video Abstract available for more insights from the authors (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A182).
Dolichoectasia of Vertebrobasilar Arteries as a Cause of Hydrocephalus and Ischemic Cerebral Stroke
Authors: Zdravković Miodrag , Kostov Milos , Petrovic Sladjana , Zdravkovic Jovana
Published: September 2017

Introduction

Dolichoectasia of vertebrobasilar artery is a rare vasculopathy, which is characterized by ectasia, elongation, and tortuosity of the basilar artery.

Case Description

A 85-year-old man was referred to the Clinic of Neurology with sudden-onset coma. A brain computed tomography scan showed remarkable fusiform dilatation with elongation of basilar artery, with compressive effect on brain stem. Autopsy confirmed existence of vertebrobasilar dolichoectasia, with organized old thrombus and partially with recent occlusive thrombosis. The histology and immunohistochemical staining were showing a loss of the elastic tissue with significant fibrosis in the tunica media and small groups of foam macrophages and cholesterol crystals in atherosclerotic plaque.

Conclusions

We presented a case of dolichoectasia of vertebrobasilar artery with an obstructive hydrocephalus, due to direct compression on pons and midbrain, which is an extremely rare entity. This case had been analyzed during the patient's life through clinical, laboratory, and radiology examinations and after he died through autopsy.
Autologous Fat Injection versus Lundborg Resection Arthroplasty for the Treatment of Trapeziometacarpal Joint Osteoarthritis
Authors: Erne Holger C. , Cerny Michael K. , Ehrl Denis , Bauer Anna T. , Schmauss Verena , Moog Philipp , Broer Peter N. , Loew Steffen , Schmauss Daniel
Published: September 2017

Background:

Various operative approaches exist for treatment of trapeziometacarpal joint osteoarthritis. The aim of this study was to compare the results of Lundborg resection arthroplasty with solely autologous fat injection.

Methods:

Twenty-one patients with symptomatic osteoarthritis of the trapeziometacarpal joint (Eaton-Littler classification stages III/IV) underwent either a Lundborg resection arthroplasty (n = 12) or autologous fat injection into the trapeziometacarpal joint (n = 9). Both groups were comparable regarding demographic and clinical data. Patient records were evaluated retrospectively regarding operative time; Disabilities of the Arm, Shoulder, and Hand questionnaire score; postoperative time until resolution of symptoms; pain level; grip and pinch force; and satisfaction with the treatment.

Results:

Both groups had similar length of follow-up of at least 12 months. The duration of the operation was significantly shorter in the fat group (13 ± 5 minutes) compared with the resection group (31 ± 5 minutes) (p < 0.05). The Disabilities of the Arm, Shoulder, and Hand questionnaire score (resection group, 21.9 ± 6.2; fat group, 24.0 ± 5.0) and the pain level at follow-up (resection group, 1.0 ± 0.7; fat group, 2.9 ± 0.8) were comparable (p > 0.05). The time until complete resolution of symptoms was significantly shorter in the fat group (1.7 ± 2.1 months) compared with the resection group (5.7 ± 3.1 months) (p < 0.05). Grip and pinch strength and overall satisfaction with the treatment were comparable (p > 0.05).

Conclusion:

Both autologous fat grafting and Lundborg resection arthroplasty resulted in improved function of the operative hand and a clear reduction of symptoms, whereas autologous fat injection seems to have advantages attributable to a shorter time until resolution of symptoms and shorter operative times.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
22 Cases of Breast Implant–Associated ALCL: Awareness and Outcome Tracking from the Italian Ministry of Health
Authors: Campanale Antonella , Boldrini Rosaria , Marletta Marcella
Published: September 2017

Background:

To date, 359 cases of anaplastic large cell lymphoma (ALCL) in women with breast implants (breast implant–associated ALCL [BIA-ALCL]) worldwide have been reported among more than 10 million patients who have received implants, but health care authorities suspect this is a possible underestimation, and the limited number of cases makes it difficult to clarify its cause. The General Directorate of Medical Devices and Pharmaceutical Services of the Italian Ministry of Health has examined and studied the Italian BIA-ALCL cases.

Methods:

An official document has been diffused to all medical associations, aiming at encouraging all physicians to notify each BIA-ALCL case. A retrospective study has been performed on the notified BIA-ALCL cases collected in the database named Dispovigilance.

Results:

Research on Dispovigilance returns a list of 22 BIA-ALCL cases. The mean patient age was 49.6 years (range, 30 to 71 years). The average time to the onset of the symptoms was 6.8 years (range, 1 to 22 years). The average time to diagnosis was 7.8 years (range, 4 to 22 years). The estimated incidence of the Italian BIA-ALCL cases related to 2015 is 2.8 per 100,000 patients.

Conclusions:

The pathogenesis of BIA-ALCL remains unknown. The establishment of a national breast implant registry is needed to better understand some aspects of this disease. Future genetic studies on the population affected could clarify why only some patients with implants develop this disease.
The Effect of Perinatal Gadolinium-Based Contrast Agents on Adult Mice Behavior
Authors: Khairinisa Miski Aghnia , Takatsuru Yusuke , Amano Izuki , Erdene Khongorzul , Nakajima Takahito , Kameo Satomi , Koyama Hiroshi , Tsushima Yoshito , Koibuchi Noriyuki
Published: September 2017

Objectives

The aim of this study was to examine the effects of perinatal exposure to gadolinium (Gd)-based contrast agents (GBCAs) on the behavior of adulthood offspring.

Materials and Methods

Pregnant Balb/C mice (n = 5 per group) were intravenously injected with gadoterate meglumine (Magnescope, macrocyclic GBCA), gadodiamide (Omniscan, linear GBCA), or vehicle from pregnancy day 15 to 19, corresponding to embryonic day 15 to 19 of the fetus, at 2 mmol/kg body weight per day. Brain samples from dams and pups were collected on postpartum day 28. The total Gd concentration was quantified by inductively coupled plasma-mass spectrometry (dams, n = 3; gadoterate meglumine-treated pups group, n = 9; and gadodiamide-treated pups group, n = 10). Behavioral testing of offspring was started on postpartum day 70 (control group, n = 22; gadoterate meglumine-treated group, n = 23; and gadodiamide-treated group, n = 20).

Results

Higher levels of Gd retention were observed in dams and pups in the gadodiamide-treated group. Perinatal exposure to GBCAs caused anxiety-like behavior, disrupted motor coordination, impaired memory function, stimulated tactile sensitivity, and decreased muscle strength, particularly in the gadodiamide-treated group.

Conclusions

In the present study, we showed that Gd was transferred to pups and was retained in their brain during postnatal development. Gadolinium retention may lead to impaired brain development. These findings indicate that the use of GBCAs in pregnant women should be avoided because it may have adverse effects on the fetus, particularly on brain development.
ACR–SPR–STR Practice Parameter for the Performance of Cardiac Positron Emission Tomography - Computed Tomography (PET/CT) Imaging
Authors: Subramaniam Rathan M. , Janowitz Warren R. , Johnson Geoffrey B. , Lodge Martin A. , Parisi Marguerite T. , Ferguson Mark R. , Hellinger Jeffrey C. , Gladish Gregory W. , Gupta Narainder K.
Published: September 2017

This clinical practice parameter has been developed collaboratively by the American College of Radiology (ACR), the Society for Pediatric Radiology (SPR), and the Society of Thoracic Radiology (STR). This document is intended to act as a guide for physicians performing and interpreting positron emission tomography–computed tomography (PET/CT) of cardiac diseases in adults and children. The primary value of cardiac PET/CT imaging include evaluation of perfusion, function, viability, inflammation, anatomy, and risk stratification for cardiac-related events such as myocardial infarction and death. Optimum utility of cardiac PET/CT is achieved when images are interpreted in conjunction with clinical information and laboratory data. Measurement of myocardial blood flow, coronary flow reserve and detection of balanced ischemia are significant advantages of cardiac PET perfusion studies. Increasingly cardiac PET/CT is used in diagnosis and treatment response assessment for cardiac sarcoidosis.
A Shift in the Orbit: Immediate Endoscopic Reconstruction After Transnasal Orbital Tumors Resection
Authors: Colletti Giacomo , Saibene Alberto M. , Pessina Federico , Duvina Marco , Allevi Fabiana , Felisati Giovanni , Biglioli Federico
Published: September 2017

Endoscopic endonasal resection of orbital lesions is a safe and common approach. Nevertheless, medial orbital wall defects following the procedure are not routinely addressed, potentially leading to diplopia and enophthalmos. In this article, the authors propose a new technique for purely endoscopic endonasal reconstruction of orbital wall defects following endoscopic endonasal resection of orbital lesions.

The patient, a 43-year-old male, suffering from right exophthalmos and diplopia due to a venous malformation of the right orbit underwent endoscopic endonasal resection of the mass. Excision was followed by immediate transnasal endoscopic reconstruction with a commercially available porous polyethylene mesh (Medpor).

The postoperative course was uneventful. The patient did not report any residual orbital asymmetry or diplopia. No recurrence of the venous malformation, mesh infection, or reconstruction instability was reported during the follow-up.

The authors believe that this new technique could spur head and neck surgeons in strategically rethinking their approach to orbital tumors, proposing reconstruction to patients on a routine basis, and developing even more reliable and manageable solutions.
Immediate Dental Implant Placement After Removal of Complex Odontoma
Authors: de Souza Batista Fábio Roberto , de Souza Batista Victor Eduardo , Vechiato-Filho Aljomar José , Tieghi Neto Victor , Figueira Jéssica Araújo , Verri Fellippo Ramos
Published: September 2017

The aim of the authors was to report a clinical case about immediate implant placement after the removal of complex odontoma. A 35-year-old female patient presented to private service complaining about absence of lower right first premolar. The computed tomographic showed radiopaque attenuation, surrounded by a narrow radiolucency in the area of dental absence, suggesting a mineralized lesion. The surgical removal of lesion was performed by intraoral access with general anesthesia and the implant of 3.75 × 10 mm (Neodent) was placed with the aid of a surgical guide, following the drill sequence established by the manufacturer. No complications were observed after 1 year with the prosthetic rehabilitation.
Impact of Septoplasty on Eustachian Tube Functions
Authors: Akyildiz Metin Yüksel , Özmen Ömer Afşin , Demir Uygar Levent , Kasapoğlu Fikret , Coşkun Hamdi Hakan , Basut Oğuz Ibrahim , Siğirli Deniz
Published: September 2017

Objective:

To evaluate the impact of nasal septum deviation (NSD) and septoplasty on eustachian tube (ET) functions.

Material and Methods:

The study was designed as a prospective controlled study and conducted in a tertiary referral center. A study group of 25 patients who were scheduled for septoplasty for NSD; and a control group of 25 healthy individuals having no ear or nose symptoms were formed. Tympanometric analysis of ET function, subjective and objective analysis of nasal functions with acoustic rhinometry and rhinomanometry were performed. Patients in study group underwent nasal surgery and tests were repeated at postoperative 1st and 3rd months.

Results:

Eustachian tube functions of study group were significantly worse than the control group (P = 0.032). ET functions were found to be poorer as the nasal airway resistances increase which was found to be close to significance (P = 0.056). One and 3 months after corrective surgery, both nasal airway functions and ET functions improved significantly reaching to the level of control group.

Conclusions:

Nasal septum deviation was associated with higher rates of ET dysfunction, which could be improved by the nasal surgery. However, in some patients, nasal surgery itself caused ET dysfunction in the early postoperative period.
Metformin Exerts Beneficial Effects in Hemorrhagic Shock in An AMPKα1-Independent Manner
Authors: Kim Paul , Piraino Giovanna , O’Connor Michael , Hake Paul W. , Wolfe Vivian , Lahni Patrick , Zingarelli Basilia
Published: September 2017

Despite therapeutic advances in hemorrhagic shock, mortality from multiple organ failure remains high. AMP-activated protein kinase (AMPK) is involved in cellular energy homeostasis. Two catalytic subunits, α1 and α2, have been identified, with α1 subunit largely expressed in major organs. Here, we hypothesized that genetic deficiency of AMPKα1 worsens hemorrhage-induced multiple organ failure. We also investigated whether treatment with metformin, a clinically used drug for metabolic homeostasis, affords beneficial effects. AMPKα1 wild-type (WT) and knock-out mice (KO) were subjected to hemorrhagic shock by blood withdrawing followed by resuscitation with shed blood and Lactated Ringer's solution and treatment with vehicle or metformin. Mice were sacrificed at 3 h after resuscitation. Compared with vehicle-treated WT animals, KO animals exhibited a more severe hypotension, higher lung and liver injury and neutrophil infiltration, and higher levels of plasma inflammatory cytokines. Metformin treatment ameliorated organ injury and mean arterial blood pressure in both WT and KO mice, without affecting systemic cytokine levels. Furthermore, metformin treatment reduced liver lipid peroxidation and increased levels of complex II cosubstrate FAD and levels of ATP in WT and KO mice. Beneficial effects of metformin were associated with organ-specific nuclear-cytoplasmic shuttling and activation of liver kinase B1 and AMPKα2. Thus, our data suggest that AMPKα1 is an important regulator of hemodynamic stability and organ metabolic recovery during hemorrhagic shock. Our data also suggest that metformin affords beneficial effects, at least in part, independently of AMPKα1 and secondary to AMPKα2 activation, increase of Complex II function and reduction of oxidative stress.
Laparoscopy for Trauma and the Changes in its Use From 1990 to 2016: A Current Systematic Review and Meta-Analysis
Authors: Cirocchi Roberto , Birindelli Arianna , Inaba Kenji , Mandrioli Matteo , Piccinini Alice , Tabola Renata , Carlini Luigi , Tugnoli Gregorio , Di Saverio Salomone
Published: September 2017

Background:

The role of laparoscopy in the diagnosis and treatment of stable abdominal trauma patients is still a matter of serious debate and only incomplete data are available.

Materials and Methods:

We performed a systematic review and meta-analysis of the literature between January 1990 and August 2016.

Results:

Overall, 9817 laparoscopies were performed for abdominal trauma; only 26.2% of the cases were converted to a laparotomy. The incidence of therapeutic laparotomies showed a reduction from 69% to 47.5%, whereas the incidence of therapeutic laparoscopies increased from 7.2% to 22.7%.

The overall perioperative mortality rate was significantly lower in the laparoscopy group [odds ratio (M-H, random); 95% confidence interval, 0.35 (0.26-0.48)]. The same group showed shorter length of hospital stay [odds ratio (M-H, random); 95% confidence interval, −3.48 (−8.91 to 1.96)].

Conclusions:

This systematic review shows a significant decrease in the use of laparoscopy in trauma patients. Most likely the widespread use of imaging techniques allows a more accurate selection of patients for diagnostic laparoscopy. Infact, a reduction in incidence of nontherapeutic laparotomies is evident in these selected patients undergoing diagnostic laparoscopy. Moreover, the literature reported an increasing trend of therapeutic laparoscopy, demonstrating that it is safe and effective. The small number and poor quality of the studies identified, the retrospective observational nature of the studies (low level of evidence), the high risk of bias, and the high heterogeneity of some outcomes make the applicability of the results of this meta-analysis unclear.
Advances in delivery of ambulatory autologous stem cell transplantation for multiple myeloma
Authors: Khouri Jack , Majhail Navneet S.
Published: September 2017

Purpose of review

Autologous stem cell transplantation (ASCT) is generally performed in the inpatient setting in its entirety. Several centers have demonstrated the feasibility of performing ASCT for myeloma in the ambulatory setting. We review the safety, cost-effectiveness, complications and outcomes of outpatient ASCT for myeloma.

Recent findings

Published studies are heterogeneous but suggest that outpatient ASCT for myeloma is cost-effective and associated with a shorter or no initial hospitalization, albeit there is a high rate of readmission for complications. The transplant-related mortality rate is less than 1%. Stringent patient selection criteria that include emphasis on functional status, caregiving support and psychosocial aspects for each patient are critical for identifying patients most appropriate for ASCT in the ambulatory setting. There exists considerable variability in outpatient transplant models and supportive care guidelines and data do not support preference for one delivery model over another. Survival and other transplant-related outcomes have not been reported widely and whether patients fare better with outpatient transplantation remains to be explored.

Outpatient ASCT for multiple myeloma is feasible and well tolerated in selected patients. Several care models for outpatient ASCT exist and can be implemented based on transplant resources and preference.
Spiritual needs of patients with cancer in palliative care: an integrative review
Authors: Mesquita Ana Cláudia , Chaves Érika de Cássia Lopes , Barros Guilherme Antônio Moreira de
Published: September 2017

Purpose of review

The experience of a life crisis, such as the experience of end-of-life terminality whenever facing cancer can make the spiritual needs of patients clear. The goal of this revision was to synthesize the existing evidence regarding the spiritual needs of patients with cancer in palliative care.

Recent findings

An integrated revision of the literature was conducted regarding the database sources from PubMed, CINAHL, EMBASE, LILACS and Scopus, without publishing year restrictions. There were 16 primary studies included. A total of 1469 patients have been evaluated, whereas eight groups of spiritual needs have been identified: finding the meaning and purpose of life; finding the meaning in experiencing the disease; being connected to other people, God and nature; having access to religious/spiritual practices; physical, psychological, social and spiritual wellbeing; talking about death and the experience of dying; making the best out of their time; being independent and being treated like a normal person.

It is essential to pay attention to patients’ spiritual dimensions regarding palliative care. Therefore, patients’ spiritual needs must be identified and remedied or mitigated. It is necessary to develop studies that find specific strategies and interventions for the treatment of these needs.
Perioperative Outcomes, Complications, and Efficacy of Robotic-Assisted Prolapse Repair: A Single Institution Study of 196 Patients
Authors: Gupta Priyanka , Ehlert Michael , Bartley Jamie , Gilleran Jason , Killinger Kim A. , Boura Judith A. , Nagaraju Pradeep , Fischer Melissa
Published: September 2017

Introduction

Abdominal pelvic organ prolapse repair is efficacious for uterovaginal and apical prolapse. We describe the safety and efficacy of robotic prolapse repair in a large teaching institution.

Methods

Consecutive robotic-assisted prolapse repairs at a single institution between 2006 and 2014 were retrospectively reviewed for patient characteristics, operative information, and outcomes.

Results

A total of 196 women (mean age, 61 ± 9 years) underwent robotic prolapse repair (189 sacrocolpopexy, 6 sacrohysteropexy, 1 enterocele repair). Concomitant procedures included hysterectomy (88), midurethral sling (84), and/or Burch colposuspension (7). Mean odds ratio time was 242 ± 69.9 minutes, and median length of stay was 1 day. Intraoperative complications were as follows: cystotomy (4), vaginotomy (4), conversion to open (2), bowel injury/aborted (1), adhesions/aborted (1), and ureteral injury (1). Women with complications had greater blood loss than those without complications (P = 0.0015). Immediate (<30 days) postoperative complications were rare: port-site hernia (2), discitis (1), ileus (1), and ulnar neuropraxia (3). At median follow-up of 9 months (range, 0–85 months), 14 women had recurrent grade 3 prolapse, and 4 had grade 2 apical prolapse. Nine of 14 women had additional prolapse repair at a mean of 9.5 ± 6.3 months. Vaginal mesh exposure was detected in 12 (6.3%) of 192 women. There were 6 procedures for mesh exposure and 2 procedures for exposed sutures. One mesh erosion into the bladder required open excision.

Conclusions

In this large series of robotic prolapse repair, complications are infrequent. Short-term apical outcomes are excellent. Few women required additional compartment repairs within 1 year with 6% rate of mesh exposure.
Evidence of semantic processing impairments in behavioural variant frontotemporal dementia and Parkinson's disease
Authors: Cousins Katheryn A.Q. , Grossman Murray
Published: September 2017

Purpose of review

Category-specific impairments caused by brain damage can provide important insights into how semantic concepts are organized in the brain. Recent research has demonstrated that disease to sensory and motor cortices can impair perceptual feature knowledge important to the representation of semantic concepts. This evidence supports the grounded cognition theory of semantics, the view that lexical knowledge is partially grounded in perceptual experience and that sensory and motor regions support semantic representations. Less well understood, however, is how heteromodal semantic hubs work to integrate and process semantic information.

Recent findings

Although the majority of semantic research to date has focused on how sensory cortical areas are important for the representation of semantic features, new research explores how semantic memory is affected by neurodegeneration in regions important for semantic processing. Here, we review studies that demonstrate impairments to abstract noun knowledge in behavioural variant frontotemporal degeneration (bvFTD) and to action verb knowledge in Parkinson's disease, and discuss how these deficits relate to disease of the semantic selection network.

Findings demonstrate that semantic selection processes are supported by the left inferior frontal gyrus (LIFG) and basal ganglia, and that disease to these regions in bvFTD and Parkinson's disease can lead to categorical impairments for abstract nouns and action verbs, respectively.
Update on tauopathies
Authors: Lebouvier Thibaud , Pasquier Florence , Buée Luc
Published: September 2017

Purpose of review

The purpose of this review is to provide an update on the role of tau beyond the stabilization of microtubules and on the clinical, pathological, diagnostic and therapeutic aspects of tauopathies.

Recent findings

Beyond its function as a microtubule-associated tau protein, tau is also involved in gene regulation, signal transduction and metabolism. Experimental models allow for the development of new diagnostic and therapeutic tools. Tauopathies encompass different disorders that may manifest with various clinical syndromes. Differential diagnosis with other proteinopathies is still challenging. Cerebrospinal fluid biomarkers and radiotracers were extensively studied in the last year. Although diagnostic accuracy remains deceiving in non-Alzheimer's disease tauopathies, positron emission tomography tau tracers could be used to monitor disease progression.

Despite the advent of novel therapeutic approaches and the increasing number of clinical trials in tauopathies, accurate clinical diagnosis is still an unmet need and better tau biomarkers are still desperately needed. Although primary taupathies are rare and heterogeneous disorders, their combined prevalence and the importance of tau disorder in Alzheimer's disease and secondary tauopathies makes research on tauopathy a priority – because it could benefit many patients.
Pathways of DNA unlinking: A story of stepwise simplification
Authors: Stolz Robert , Yoshida Masaaki , Brasher Reuben , Flanner Michelle , Ishihara Kai , Sherratt David J. , Shimokawa Koya , Vazquez Mariel
Published: September 2017

InEscherichia coliDNA replication yields interlinked chromosomes. Controlling topological changes associated with replication and returning the newly replicated chromosomes to an unlinked monomeric state is essential to cell survival. In the absence of the topoisomerase topoIV, the site-specific recombination complex XerCD-dif-FtsK can remove replication links by local reconnection. We previously showed mathematically that there is a unique minimal pathway of unlinking replication links by reconnection while stepwise reducing the topological complexity. However, the possibility that reconnection preserves or increases topological complexity is biologically plausible. In this case, are there other unlinking pathways? Which is the most probable? We consider these questions in an analytical and numerical study of minimal unlinking pathways. We use a Markov Chain Monte Carlo algorithm with Multiple Markov Chain sampling to model local reconnection on 491 different substrate topologies, 166 knots and 325 links, and distinguish between pathways connecting a total of 881 different topologies. We conclude that the minimal pathway of unlinking replication links that was found under more stringent assumptions is the most probable. We also present exact results on unlinking a 6-crossing replication link. These results point to a general process of topology simplification by local reconnection, with applications going beyond DNA.
seq-seq-pan: Building a computational pan-genome data structure on whole genome alignment
Authors: Jandrasits Christine , Dabrowski Piotr W , Fuchs Stephan , Renard Bernhard Y
Published: September 2017

Background

The increasing application of next generation sequencing technologies has led to the availability of thousands of reference genomes, often providing multiple genomes for the same or closely related species. The current approach to represent a species or a population with a single reference sequence and a set of variations cannot represent their full diversity and introduces bias towards the chosen reference. There is a need for the representation of multiple sequences in a composite way that is compatible with existing data sources for annotation and suitable for established sequence analysis methods. At the same time, this representation needs to be easily accessible and extendable to account for the constant change of available genomes.

Results

We introduce seq-seq-pan, a framework that provides methods for adding or removing new genomes from a set of aligned genomes and uses these to construct a whole genome alignment. Throughout the sequential workflow the alignment is optimized for generating a representative linear presentation of the aligned set of genomes, that enables its usage for annotation and in downstream analyses.

Conclusions

By providing dynamic updates and optimized processing, our approach enables the usage of whole genome alignment in the field of pan-genomics. In addition, the sequential workflow can be used as a fast alternative to existing whole genome aligners. seq-seq-pan is freely available athttps://gitlab.com/groups/rki_bioinformatics
Inferring the selection window in antimicrobial resistance using deep mutational scanning data and biophysics-based fitness models
Authors: Dasmeh Pouria , Ton Anh-Tien , Quach Caroline , Serohijos Adrian W.R.
Published: September 2017

Mutant-selection window (MSW) hypothesis in antimicrobial resistance implies a range for antimicrobial concentration that promotes selection of single-step resistant mutants. Since the inception and experimental verification, MSW has been at the forefront of strategies to minimize development of antimicrobial resistance (AR). Setting the upper and lower limits of MSW requires an understanding of the dependence of selection coefficient of arising mutations to antimicrobial concentration. In this work, we employed a biophysics-based and experimentally calibrated fitness model to estimate MSW in the case of Ampicillin and Cefotaxime resistance in E.coli TEM-1 beta lactamase. In line with experimental observations, we show that selection is active at very low levels of antimicrobials. Furthermore, we elucidate the dependence of MSW to catalytic efficiency of mutants, fraction of mutants in the population and discuss the role of population genetic parameters such as population size and mutation rate. Altogether, our analysis and formalism provide a predictive model of MSW with direct implications in the design of dosage strategies.
Systematic Mutagenesis of Serine Hydroxymethyltransferase Reveals an Essential Role in Nematode Resistance
Authors: Kandoth Pramod K. , Liu Shiming , Prenger Elizabeth , Ludwig Andrew , Lakhssassi Naoufal , Heinz Robert , Zhou Zhou , Howland Amanda , Gunther Joshua , Eidson Samantha , Dhroso Andi , LaFayette Peter , Tucker Donna , Johnson Sarah , Anderson James , Alaswad Alaa , Cianzio Silvia R. , Parrott Wayne A. , Korkin Dmitry , Meksem Khalid , Mitchum Melissa G.
Published: September 2017

Rhg4 is a major genetic locus that contributes to soybean cyst nematode (SCN) resistance in the Peking-type resistance of soybean (Glycine max), which also requires the rhg1 gene. By map-based cloning and functional genomic approaches, we previously showed that the Rhg4 gene encodes a predicted cytosolic serine hydroxymethyltransferase (GmSHMT08); however, the novel gain of function of GmSHMT08 in SCN resistance remains to be characterized. Using a forward genetic screen, we identified an allelic series of GmSHMT08 mutants that shed new light on the mechanistic aspects of GmSHMT08-mediated resistance. The new mutants provide compelling genetic evidence that Peking-type rhg1 resistance in cv Forrest is fully dependent on the GmSHMT08 gene and demonstrates that this resistance is mechanistically different from the PI 88788-type of resistance that only requires rhg1. We also demonstrated that rhg1-a from cv Forrest, although required, does not exert selection pressure on the nematode to shift from HG type 7, which further validates the bigenic nature of this resistance. Mapping of the identified mutations onto the SHMT structural model uncovered key residues for structural stability, ligand binding, enzyme activity, and protein interactions, suggesting that GmSHMT08 has additional functions aside from its main enzymatic role in SCN resistance. Lastly, we demonstrate the functionality of the GmSHMT08 SCN resistance gene in a transgenic soybean plant.
Crystal structure of ochraceolide A isolated fromElaeodendron trichotomum(Turcz.) Lundell
Authors: Herrera-España Angel D. , Mena-Rejón Gonzalo J. , Hernández-Ortega Simón , Quijano Leovigildo , Mirón-López Gumersindo
Published: September 2017

The title compound, C30H44O3[systematic name: 6aR,6 bR,8aS,9aR,12aR,14bR)-4,4,6a,6;b,8a,14b-hexamethyl-12-methyleneicosahydro-3H-phenanthro[1′,2′:6,7]indeno[2,1-b]furan-3,11(2H)-dione], is a triterpene lactone, which was isolated from dichloromethane extract ofElaeodendron trichotomum(Turcz.) Lundell (celastraceae) stem bark. The compound has a lupane skeleton and consists of four fused six-membered rings and two five-membered rings. In the crystal, molecules are linked by weak C—H...O hydrogen bonds into a three-dimensional network. The configuration of ochraceolide A was proposed based on analogue compounds which belong to the lupane type.