bluuebunny/crossref_metadata_2025 huggingface dataset:
Altering the allosteric pathway in IGPS suppresses millisecond motions and catalytic activity
Authors: Lisi George P. , East Kyle W. , Batista Victor S. , Loria J. Patrick
Published: April 2017

Significance

The enzyme imidazole glycerol phosphate synthase (IGPS) fromThermotoga maritimais a potential therapeutic target absent in mammals but present in bacteria, plants, and fungi. The reported findings on how to affect allosteric pathways and suppress catalytic activity are particularly relevant to establish and alter allosteric mechanisms that could represent targets for drug discovery. In particular, many plant and human pathogens that infect the immunocompromised patient have an IGPS that is highly homologous to theSaccharomyces cerevisiaeandT. maritimaenzymes. It has also been demonstrated that gene knockouts of IGPS subunit HisF can increase the susceptibility of bacteria to β-lactam antibiotics and lessen their infectivity.
Complex fluid flow and heat transfer analysis inside a calandria based reactor using CFD technique
Authors: Kulkarni P. S.
Published: April 2017

Series of numerical experiments have been carried out on a calandria based reactor for optimizing the design to increase the overall heat transfer efficiency by using Computational Fluid Dynamic (CFD) technique. Fluid flow and heat transfer inside the calandria is governed by many geometric and flow parameters like orientation of inlet, inlet mass flow rate, fuel channel configuration (in-line, staggered, etc.,), location of inlet and outlet, etc.,. It was well established that heat transfer is more wherever forced convection dominates but for geometries like calandria it is very difficult to achieve forced convection flow everywhere, intern it strongly depends on the direction of inlet jet. In the present paper the initial design was optimized with respect to inlet jet angle, the optimized design has been numerically tested for different heat load mass flow conditions. To further increase the heat removal capacity of a calandria, further numerical studies has been carried out for different inlet geometry. In all the analysis same overall geometry size and same number of tubes has been considered. The work gives good insight into the fluid flow and heat transfer inside the calandria and offer a guideline for optimizing the design and/or capacity enhancement of a present design.
Fast radio bursts as pulsar lightning
Authors: Katz J. I.
Published: April 2017

There are striking phenomenological similarities between fast radio bursts (FRBs) and lightning in the Earth's and planetary atmospheres. Both have very low duty factors, ≲10−8–10−5 for FRBs and (very roughly) ∼10−4 for the main return strokes in an active thundercloud. Lightning occurs in an electrified insulating atmosphere when a conducting path is created by and permits current flow. FRBs may occur in neutron star magnetospheres whose plasma is believed to be divided by vacuum gaps. Vacuum is a perfect insulator unless electric fields are sufficient for electron–positron pair production by curvature radiation, a high-energy analogue of electrostatic breakdown in an insulating gas. FRB may be ‘electrars’ powered by the release of stored electrostatic energy, counterparts to soft gamma repeaters powered by the release of stored magnetostatic energy (magnetars). This frees pulsar FRB models from the constraint that their power not exceeds the instantaneous spin-down power. Energetic constraints imply that the sources of more energetic FRBs have shorter spin-down lifetimes, perhaps even less than the 3 yr over which FRB 121102 has been observed to repeat.
Male Gender Associated with Post-Treatment Seizure Risk of Pediatric Arteriovenous Malformation Patients
Authors: Yang Wuyang , Westbroek Erick M. , Anderson-Keightly Heather , Caplan Justin M. , Rong Xiaoming , Hung Alice L. , Braileanu Maria , Wang Joanna Y. , Colby Geoffrey P. , Coon Alexander L. , Tamargo Rafael J. , Ahn Edward S. , Huang Judy
Published: April 2017

BACKGROUND: Seizure risk has not been fully characterized in pediatric patients with arteriovenous malformations (AVMs).

OBJECTIVE: To describe the progression and risk factors of post-treatment seizure in children with AVMs.

METHODS: We retrospectively reviewed pediatric patients diagnosed with intracranial AVMs at our institution between 1990 and 2013. Clinical and angiographic variables were included in univariate and multivariate Cox proportional hazard models to explore risk factors associated with time-related seizure outcomes. The outcome event is defined as first seizure occurrence after initial treatment. Kaplan–Meier survival curve is depicted for each significant variable, and survival differences were confirmed by Log-rank test.

RESULTS: We included 90 pediatric patients with complete data in our study cohort. Average age is 13.3 ± 3.8 years with 43.3% male patients. Thirty-seven patients had a hemorrhagic presentation, and 39 patients presented with seizure. Post-treatment seizure occurred in 33 patients (36.7%) over an average follow-up period of 8.1 ± 10.6 years; average time to onset is 5.3 ± 8.2 years, with partial seizures as the most common presentation. Multivariate Cox proportional hazard regression revealed seizure presentation (P = .005), male gender (P = .026), and nonconservative treatment modality to be significantly associated with earlier onset of post-treatment seizure after adjusting for AVM location and deep venous drainage. Overall annualized seizure risk is 7.4% for patients with pretreatment seizure, and 1.4% for those without.

CONCLUSION: Risk of seizure persists after treatment in pediatric AVM patients. Seizure presentation, male gender, and nonconservative management are associated with increased risk of post-treatment seizure. Early identification of these risk factors provides important information for determining seizure management strategies.
Quality of Life in Patients with Vestibular Schwannomas Following Gross Total or Less than Gross Total Microsurgical Resection: Should We be Taking the Entire Tumor Out?
Authors: Link Michael J , Lund-Johansen Morten , Lohse Christine M , Driscoll Colin L W , Myrseth Ehrling , Tveiten Oystein Vesterli , Carlson Matthew L
Published: April 2017

BACKGROUND

The goal of microsurgical removal of a vestibular schwannoma is to completely remove the tumor, to provide long-term durable cure. In many cases, less than gross total resection (GTR) is performed to preserve neurological, and especially facial nerve function.

OBJECTIVE

To analyze long-term quality of life (QoL) in a cohort of patients who received either GTR or less than GTR.

METHODS

Patients operated for vestibular schwannoma less than 3.0 cm in posterior fossa diameter at 1 of 2 international tertiary care centers were surveyed using generic and disease-specific QoL instruments.

RESULTS

A total of 143 patients were analyzed. GTR was performed in 122, and 21 underwent less than GTR. QoL was assessed at a mean of 7.7 yr after surgery (interquartile range: 5.7-9.6). Patients who underwent GTR had smaller tumors; otherwise, there were no baseline differences between groups. Patients who underwent GTR, after multivariable adjustment for baseline features and facial nerve and hearing outcomes, reported statistically significantly better Short Form Health Survey-36 (SF-36) physical and mental scores, Patient-Reported Outcomes Measurement Information System (PROMIS-10) physical and mental scores, and Penn Acoustic Neuroma Quality of Life (PANQOL) facial, energy, general health, and total scores compared to patients receiving less than GTR.

CONCLUSION

GTR is associated with better QoL using the general QoL measures SF-36 and PROMIS-10 and the disease-specific PANQOL, even after controlling for baseline and outcome differences. This is especially significant in the assessment of mental health, indicating there may indeed be a psychological advantage to the patient that translates to overall well-being to have the entire tumor removed if microsurgical resection is undertaken.
Intraoperative Angiography for Arteriovenous Malformation Resection in the Prone and Lateral Positions, Using Upper Extremity Arterial Access
Authors: Nossek Erez , Chalif David J. , Buciuc Razvan , Gandras Eric J. , Anderer Erich G. , Insigna Sal , Dehdashti Amir R. , Setton Avi
Published: April 2017

BACKGROUND: Intraoperative angiography is routinely utilized for aneurysms and arteriovenous malformations (AVMs) to verify complete occlusion and resection. Surgery for spinal and posterior fossa neurovascular lesions is usually performed in prone position. Intraoperative angiography in the prone position is challenging and there is no standardized protocol for this procedure.

OBJECTIVE: To describe our experience with intraoperative angiography in the prone and lateral positions, using upper extremity arterial access.

METHODS: We reviewed our experience with intraoperative angiography in the prone position between 2014 and 2015, where vascular access was obtained via the upper extremity arteries. Patients were treated in a hybrid endovascular operating room. High cervical and intracranial lesions were studied via brachial or radial access. All accesses were obtained using ultrasonographic guidance and a small caliber arterial sheath (4F).

RESULTS: Five patients were treated in the prone and lateral positions using brachial/radial artery access. Patients harbored cerebellar AVM, lateral medullary AVM, cervical arteriovenous fistula (AVF), tentorial dural AVF, and tentorial-incisural dural AVF. Patients were positioned prone (n = 2), semiprone (n = 2), and lateral (n = 1) for the surgery. Three patients were treated via right brachial artery access. Two patients were treated via radial arteries access. All patients tolerated the procedures without technical or clinical complications. Intraoperative angiography verified complete occlusion and resection in all cases prior to surgical closure.

CONCLUSIONS: Intraoperative angiography in the prone and lateral positions using upper extremity access is an important adjunct. Brachial or radial access can be obtained safely and provides comfortable and quick approaches.
A Role of Cytokinin Transporter in Arabidopsis Immunity
Authors: Wang Shuai , Wang Shu , Sun Qi , Yang Leiyun , Zhu Ying , Yuan Yaping , Hua Jian
Published: April 2017

The phytohormone cytokinin (CK) is not only essential for plant growth and development but also impacts plant immunity. A mutant screen in a constitutively active plant immune receptor mutant snc1 (suppressor of npr1, constitutive1) identified a suppressor mutation of SNC1-induced defense responses in an ABC transporter coding gene ABCG14. ABCG14 transports CK from roots to the shoots, and the suppression of the SNC1-mediated defense response by the loss of ABCG14 is due to a deficiency of trans-zeatin (tZ)-type CK in the shoot. In addition, exogenous application of the tZ-type CK enhances disease resistance associated with increased expression of the plant immune receptor gene SNC1. Taken together, this study further established the role of tZ-type CK in disease resistance and suggests a new intersection of CKs with plant immunity at the expression regulation of a plant immune receptor gene.
Host Resistance and Chemical Control for Management of Sclerotinia Stem Rot of Soybean in Ohio
Authors: Huzar-Novakowiski Jaqueline , Paul Pierce A. , Dorrance Anne E.
Published: April 2017

Recent outbreaks of Sclerotinia stem rot (SSR) of soybean in Ohio, along with new fungicides and cultivars with resistance to this disease, have led to a renewed interest in studies to update disease management guidelines. The effect of host resistance (in moderately resistant [MR] and moderately susceptible [MS] cultivars) and chemical control on SSR and yield was evaluated in 12 environments from 2014 to 2016. The chemical treatments evaluated were an untreated check, four fungicides (boscalid, picoxystrobin, pyraclostrobin, and thiophanate-methyl), and one herbicide (lactofen) applied at soybean growth stage R1 (early flowering) alone or at R1 followed by a second application at R2 (full flowering). SSR developed in 6 of 12 environments, with mean disease incidence in the untreated check of 2.5 to 41%. The three environments with high levels of SSR (disease incidence in the untreated check >20%) were used for further statistical analysis. There were significant effects (P < 0.05) of soybean cultivar and chemical treatment on SSR levels. Significantly lower levels of SSR were observed in MR cultivars. Both boscalid and lactofen reduced SSR but did not increase yield. Pyraclostrobin increased SSR compared with the untreated check in the three environments with high levels of disease. In the six fields where SSR did not develop, chemical treatment did not increase yield, nor was the yield from the MR cultivar significantly different from the MS cultivar. For Ohio, MR cultivars alone were effective for management of SSR in soybean fields where this disease has historically occurred.
Does Music Positively Impact Preterm Infant Outcomes?
Authors: O'Toole Alexa , Francis Kim , Pugsley Lori
Published: April 2017

Background:

The hospital environment leaves preterm infants (PTIs) exposed to various stressors that can disrupt their growth and development. Developmental interventions such as music may be an important strategy to mitigate PTI's stress. This brief evaluates current evidence regarding the impact of music therapy on outcomes for PTIs.

Purpose:

The question guiding this brief is “Do various types of music therapy positively affect physiologic indicators, feeding behaviors/length of stay (LOS) and pain management outcomes for PTIs?”

Search Strategy:

CINAHL/MEDLINE Complete and PubMed databases were searched using keywords preterm infants, premature infants, preterm baby, premature baby, NICU baby, music, and music therapy. The search was limited to 5 years for English studies evaluating the effects of music therapy on physiological indicators, feeding, pain outcomes, and length of stay. The search yielded 12 studies addressing these concerns.

Findings:

Music therapy was shown to positively affect physiologic indicators, feeding, length of stay, and pain outcomes for PTIs. In addition, music decreased parental stress.

Implications for Practice:

Thoughtful consideration should be given regarding the value of diverse types of music and parental involvement when incorporating music into an individualized plan of care. Furthermore, the development of guidelines with a focus on ambient sound reduction is an important strategy when adding music as an intervention.

Implications for Research:

Further research is needed to investigate ambient sound levels in conjunction with musical interventions. In addition, the impact of various types of music, differences in gender, reduction of stress, pain for infants, and parental role in music requires further evaluation.
Quality Improvement Project to Reduce Delayed Vaccinations in Preterm Infants
Authors: Cuna Alain , Winter Lindy
Published: April 2017

Background:

Preterm infants are especially vulnerable to infectious diseases. Although vaccinations are a safe and effective measure to protect preterm infants from vaccine-preventable diseases, delays in vaccinations are not uncommon.

Purpose:

The goal of this quality improvement project was to improve on time vaccinations of preterm infants hospitalized in the neonatal intensive care unit.

Methods:

The Plan-Do-Study-Act model of quality improvement was adopted to develop, test, and implement interventions aimed at improving timely vaccination of preterm infants. The primary outcome measure of interest was the rate of on time vaccination, which was defined as the proportion of medically eligible preterm infants who received vaccinations within 2 weeks of the recommended schedule.

Results:

Baseline on time vaccination rate was only 36%. Following several Plan-Do-Study-Act cycles, a steady increase in on time vaccinations of eligible infants was observed, and a new baseline on time vaccination rate of 82% was achieved.

Implications for Practice:

Simple interventions implemented within the context of Plan-Do-Study-Act cycles are effective in improving timely vaccinations among preterm infants.

Implications for Research:

Future research that focuses on vaccinations in preterm infants is needed to further reinforce the safety and efficacy of vaccines. Effective methods on how to disseminate and apply this knowledge to practice should also be studied.

Video Abstract available at
http://links.lww.com/ANC/A27.
Noise in the Neonatal Intensive Care Unit
Authors: Casavant Sharon G. , Bernier Katherine , Andrews Sheena , Bourgoin Allison
Published: April 2017

Background:

In 2014, more than 10% of all births in the United States were preterm (born at <37-weeks' gestation). These high-risk infants will often spend weeks to months within the neonatal intensive care unit (NICU), where noise levels can easily reach 120 decibels adjusted (dBA) on a regular and sometimes consistent basis. The American Academy of Pediatrics recommends that NICU sound levels remain below 45 dBA to promote optimal growth and development.

Purpose:

The purpose of this evidence-based brief is to critically appraise the literature concerning preterm infant response to noise within the NICU as well as the use of noise interventions to improve health outcomes for the vulnerable preterm infant population.

Methods/Search Strategy:

Systematic searches of databases included the Cochrane Library, CINAHL, PubMed, and Science Direct. Included studies were appraised and then synthesized into a narrative summary.

Findings/Results:

Twenty studies met inclusion criteria for this review. While there are numerous methods that have been shown to reduce noise levels within the NICU, most NICU noise levels remain consistently above the American Academy of Pediatrics recommendations. Studies that assessed interventions found that staff reeducation was critical to sustaining appropriate noise levels.

Implications for Practice:

Implementing interventions with rigorous attention to initial and continued staff education with engagement and ownership is recommended. This review identifies gaps in intervention studies targeting vulnerable NICU populations.

Implications for Research:

While noise interventions show promise in the NICU, additional focused research is needed to further strengthen the evidence and inform clinical practice.
Preoperative acetabular angle measurement as a tool in acetabular cup positioning during total hip arthroplasty
Authors: Rodriguez Hugo A.
Published: April 2017

Background:

Acetabular cup positioning within the Lewinnek safe zone reduces the risk of complications related to prosthesis dislocation. However, it has been demonstrated that angles of abduction of the native acetabulum do not lie within this range, possibly leading to cup malpositioning. The purpose of this study was to determine whether the preoperative radiographic measurements of acetabular abduction correlate with those obtained intraoperatively with the use of an inclinometer.

Methods:

Preoperative and intraoperative angles of abduction from 100 consecutive patients who underwent total hip arthroplasty between July 2007 and November 2008. An intraclass correlation coefficient (ICC) and its 95% confidence interval (95% CI) were calculated to determine the level of agreement between the preoperative and the intraoperative angles.

Results:

Mean preoperative angle of abduction was 48.9±6.1 degrees and mean intraoperative angle was 49±5.7 degrees. The mean difference between these angles was 0.06 degrees. Twenty-eight percent of patients had preoperative angles of abduction of>50 degrees. An ICC of 0.96 (95% CI: 0.94–0.97) was obtained. This indicates that preoperative and intraoperative measures of acetabular abduction are almost identical.

Conclusions:

Preoperative and intraoperative measures of acetabular inclination are highly correlated. Measurements of acetabular inclination on preoperative plain anteroposterior radiographs of the pelvis should be considered for acetabular cup positioning during total hip arthroplasty. The systematic use of this simple, valid, and effective measurement might be useful.
Pediatric Femoral Shaft Fractures: A Multicenter Review of the AAOS Clinical Practice Guidelines Before and After 2009
Authors: Roaten John D. , Kelly Derek M. , Yellin Joseph L. , Flynn John M. , Cyr Micaela , Garg Sumeet , Broom Alexander , Andras Lindsay M. , Sawyer Jeffrey R.
Published: April 2017

Background:

To determine if the AAOS clinical practice guidelines (CPG) for the treatment of pediatric femoral shaft fractures (2009) changed treatment, we analyzed pediatric femoral shaft fractures at 4 high-volume, geographically separated, level-1 pediatric trauma centers over a 10-year period (2004 to 2013).

Methods:

Consecutive series of pediatric femoral shaft fractures (ages, birth to 18 y) treated at the 4 centers were reviewed. Treatment methods were analyzed by age and treatment method for each center and in aggregate.

Results:

Of 2646 fractures, 1476 (55.8%) were treated nonoperatively and 1170 fractures operatively. Of the operative group, flexible intramedullary nails (IMN) were used for 568 patients (21.5%), locked intramedullary nails (LIMNs) for 309 (11.7%), and plating for 188 (7.1%). In total, 105 fractures were treated with external fixation or skeletal traction. Analysis before and after the CPG publication revealed a significant increase in the use of interlocked IMNs in patients younger than 11 years (0.5% before, 3.8% after; P<0.001). Over the same time period there was an increase in surgical management, regardless of technique, for patients younger than 5 years (6.4% before, 8.4% after; P=0.206). There were considerable differences in treatment among centers: 74% of fractures treated with plating were from a single center (center A), which also contributed 68% of patients younger than 5 years treated with plating; center B had the highest rate (41%) of flexible IMN in children younger than 5 years; center C had the highest rate (63%) of LIMN in children younger than 11 years; and center D treated the fewest patients outside the CPG guidelines.

Conclusions:

Following publication of the AAOS CPG, there was a significant increase in the use of LIMNs in patients younger than 11 years old and a trend toward surgical treatment in patients younger than 5 years. The considerable variability among centers in treatment methods and adherence to the CPG highlights the need for further outcome studies to better define optimal treatment methods and perhaps update the AAOS CPG guidelines.

Level of Evidence:

Level III—therapeutic.
Clubfoot Infants Initially Thought to be Idiopathic, But Later Found Not to Be. How do They do With Nonoperative Treatment?
Authors: Richards B. Stephens , Faulks Shawne
Published: April 2017

Background:

Infants thought to be normal with idiopathic clubfeet when nonoperative treatment begins may later be found to have other complicating diagnoses. The purpose of this study was to determine the incidence of this occurrence, and to compare the clinical outcomes of these “nonidiopathic” patients with idiopathic clubfoot patients.

Methods:

Infants below 3 months old with clubfeet who were thought to be normal (idiopathic) at presentation and had ≥2-year follow-up were studied. Treatment consisted of either the Ponseti method or the French physical therapy method. In total, 789 patients with 1174 clubfeet were identified. Those who were idiopathic (group 1) were compared with those later found to be nonidiopathic (group 2). The outcomes at 2 years were assessed as good (plantigrade foot±heelcord tenotomy only), fair (limited procedures), or poor (full-posteromedial release). For those feet rated good at age 2 years, outcomes were again assessed age 5 years and above.

Results:

In total, 70 patients (8.9%) of the 789 enrolled patients were eventually found to have another disorder including neurological, syndromic, chromosomal, or spinal abnormalities. The remaining 719 idiopathic patients with 1062 clubfeet (group 1) were compared with these 70 nonidiopathic patients with 112 clubfeet (group 2). At age 2 years, in group 1 81% of the feet were rated good, 11% fair, and 8% poor, whereas in group 2 70% of the feet were rated good, 11% fair, and 19% poor (P=0.0004).

With follow-up exceeding age 5 years in those rated good at age 2 years: in group 1, 73% continued to do well, but 22% rated fair, and 5% poor. In group 2, 59% continued to do well, but 31% rated fair, and 10% poor (P=0.046).

Conclusions:

For infants with clubfeet who were initially thought to be idiopathic, nearly 9% were later found to have a complicating disorder. Despite this, these patients’ clubfeet can be expected to respond favorably to nonoperative treatment. However, they will require more surgical intervention early (by age 2 years) and later (age, 5 years and above) when compared with normal infants with idiopathic clubfeet.

Level of Evidence:

Level IV—therapeutic, case series.
Rectus Femoris Transfer Surgery Worsens Crouch Gait in Children With Cerebral Palsy at GMFCS Levels III and IV
Authors: Sousa Ted C. , Nazareth Alexander , Rethlefsen Susan A. , Mueske Nicole M. , Wren Tishya A.L. , Kay Robert M.
Published: April 2017

Background:

Previous study has shown that children with cerebral palsy (CP) functioning at Gross Motor Function Classification System (GMFCS) levels III and IV do not benefit from distal rectus femoris transfer (DRFT) due to lack of improvement in stance knee extension. The fate of knees in such subjects who do not undergo DRFT is unknown. The purpose of this study was to compare knee kinematic outcomes in patients with CP and stiff knee gait who underwent single-event multilevel surgery with and without DRFT.

Methods:

Preoperative and postoperative gait analysis data were retrospectively reviewed for ambulatory (GMFCS levels I to IV) patients with CP with crouch and stiff knee gait whom underwent single-event multilevel surgery, including hamstring lengthening either with DRFT (N=34) or without DRFT (N=40). Statistical analyses included t tests and χ2 tests, and multiple regression analysis was performed to adjust for covariates. Data were stratified by GMFCS level groups I/II and III/IV.

Results:

Improved maximum knee extension in stance was seen for both the DRFT (P=0.0002) and no DRFT groups (P≤0.0006) at GMFCS levels I/II, and the no DRFT group at GMFCS levels III/IV (P=0.02). Excessive stance knee flexion persisted for those at GMFCS level III/IV after DRFT. Maximum knee flexion in swing was maintained after DRFT, but significantly decreased in the no DRFT group (P<0.002) for both GMFCS groups. Change in total knee range of motion improved after DRFT only in the GMFCS I/II group subjects with unilateral involvement (P=0.01). Timing of maximum knee flexion in swing improved for all patients regardless of DRFT or GMFCS level group (P<0.0001).

Conclusions:

In patients with CP functioning at GMFCS levels III and IV, DRFT results in persistent crouch postoperatively. Given the importance of maintaining upright posture in these patients, we do not recommend DRFT in patients functioning at GMFCS levels III and IV.

Level of Evidence:

Level III—retrospective comparative study.
Propionibacterium acnes Incubation in the Discs Can Result in Time-Dependent Modic Changes
Authors: Shan Zhi , Zhang Xuyang , Li Shengyun , Yu Tianming , Liu Junhui , Zhao Fengdong
Published: April 2017

Study Design.

A case-control study of animal model of Modic changes (MCs) on rabbits.

Objective.

To evaluate the feasibility of inducing of MCs by injection of Propionibacterium acne (P. acnes) into the lumbar intervertebral discs of rabbits.

Summary of Background Data.

MCs have been widely observed, and assume to be closely associated with low back pain and P. acnes, but there are few animal models showing the progression of MCs.

Methods.

Ten rabbits were used for the study. The L3–4 and L4–5 discs of all rabbits were injected with 100 μL P. acnes (1.6 × 107 CFU/mL) as P. acnes group, L2–3 disc were injected with 100 μL normal saline as vehicle, and L5–6 disc was untreated (blank). MCs were investigated by magnetic resonance imaging before operation and at 2 weeks, 1, 3, 4.5, 6, and 9 months postoperatively. Following sacrifice, histological analysis, blood test and micro-computed tomography were performed. Cytokine expression in nucleus and endplate tissues was quantified using real-time polymerase chain reaction.

Results.

From 3 months postoperatively, the P. acnes group showed significantly decreased T1-weighted signal intensity, whereas the T2-weighted signal was significantly higher at 3 and 4.5 months, and then decreased remarkably at 6 and 9 months. Eleven of 20 inferior endplates were identified as type I MCs at 4.5 months, and 9 of 20 were identified as type II MCs at 9 months. Real-time polymerase chain reaction showed that expression of interleukin-1β, tumor necrosis factor α, interferon-γ, matrix metalloproteinase-9, and thrombospondin motifs-5 in the nucleus pulposus, and interleukin-1β, tumor necrosis factor α, and thrombospondin motifs-5 in the endplates, were significantly upregulated after injection of P. acnes. Histological slices of discs injected with P. acnes showed disc degeneration, endplate abnormalities, and inflammatory response, with micro-computed tomography confirming bone resorption.

Conclusion.

P. acnes infection of the disc can induce degeneration of the disc and an inflammatory response in the endplate region, presenting as MCs type I and II time dependently.

Level of Evidence: N/A
Urgent Chemotherapy for Life-Threatening Complications Related to Solid Neoplasms
Authors: Zerbib Yoann , Rabbat Antoine , Fartoukh Muriel , Bigé Naïke , Andréjak Claire , Mayaux Julien , De Prost Nicolas , Misset Benoît , Lemiale Virginie , Bruneel Fabrice , Maizel Julien , Ricome Sylvie , Jacobs Frédéric , Bornstain Caroline , Dupont Hervé , Baudin François , Azoulay Elie , Pène Frédéric
Published: April 2017

Objectives:

Solid neoplasms can be directly responsible for organ failures at the time of diagnosis or relapse. The management of such specific complications relies on urgent chemotherapy and eventual instrumental or surgical procedures, combined with advanced life support. We conducted a multicenter study to address the prognosis of this condition.

Design:

A multicenter retrospective (2001–2015) chart review.

Setting:

Medical and respiratory ICUs.

Patients:

Adult patients who received urgent chemotherapy in the ICU for organ failure related to solid neoplasms were included. The modalities of chemotherapy, requirements of adjuvant instrumental or surgical procedures, and organ supports were collected. Endpoints were short- and long-term survival rates.

Interventions:

None.

Measurements and Main Results:

One hundred thirty-six patients were included. Lung cancer was the most common malignancy distributed into small cell lung cancer (n = 57) and non-small cell lung cancer (n = 33). The main reason for ICU admission was acute respiratory failure in 111 patients (81.6%), of whom 89 required invasive mechanical ventilation. Compression and tissue infiltration by tumor cells were the leading mechanisms resulting in organ involvement in 78 (57.4%) and 47 (34.6%) patients. The overall in-ICU, in-hospital, 6-month, and 1-year mortality rates were 37%, 58%, 74%, and 88%, respectively. Small cell lung cancer was identified as an independent predictor of hospital survival. However, this gain in survival was not sustained since the 1-year survival rates of small cell lung cancer, non-small cell lung cancer, and non-lung cancer patients all dropped below 20%.

Conclusions:

Urgent chemotherapy along with aggressive management of organ failures in the ICU can be lifesaving in very selected cancer patients, most especially with small cell lung cancer, although the long-term survival is hardly sustainable.
The Association Between Visiting Intensivists and ICU Outcomes*
Authors: Whitehouse Tony , Hodson James , Pemberton Philip , Veenith Tonny , Snelson Catherine , Bion Julian , Rubenfeld Gordon D.
Published: April 2017

Objectives:

We hypothesized that intensivists unfamiliar with an ICU team and the context of that ICU would affect patient outcomes. We examined differences in mortality when ICU patients were admitted under intensivists routinely working in that ICU and compared with those admitted by intensivists familiar with an ICU elsewhere in the same hospital.

Design, Settings, and Patients:

A 5-year natural experimental crossover study involving patients admitted to four ICUs in a large U.K. teaching hospital.

Interventions:

During a period of service reconfiguration, intensivists routinely rostered to work in one ICU worked in another of the hospital’s four ICUs. “Home” intensivists were those who continued to work in their usual ICU; “visitor” intensivists were those who delivered care in an unfamiliar ICU. Patient data were obtained from electronic patient records to provide analysis on sex, age, admission Sequential Organ Failure Assessment score, date and time of admission, and admission type (elective, transfer, or unplanned).

Measurements and Main Results:

We analyzed 9,981 admissions to four separate ICUs over a 5-year period. In total, 34.5% of patients were admitted by intensivists working in nonfamiliar surroundings. Visitor intensivists admitted patients with similar age and gender distributions but with greater physiologic derangement (mean Sequential Organ Failure Assessment score, 4.1 ± 2.8 vs 3.9 ± 2.8; p < 0.001) than home intensivists. Overall ICU mortality rates were higher in visitor intensivists, albeit not significantly so (11.5% vs 10.2%; p = 0.052). However, when the ICUs were analyzed separately, visitor mortality rates were found to be significantly higher than for home intensivists in two of the four ICUs (p = 0.017, 0.006). A multivariable analysis adjusting for confounding factors and the clustering of consultants revealed that the overall mortality rate was significantly higher for visitors (odds ratio, 1.18; 95% CI, 1.02–1.37; p = 0.024). A significant interaction between the ICU and visitor status was also detected (p = 0.046), with the visitor effect remaining significant in the two ICUs identified previously (both p = 0.009).

Conclusions:

Visitor intensivists in some ICUs were associated with higher mortality. The reasons are unknown but could relate to intensivists’ practices, unfamiliarity with the patients, or the interaction with the interprofessional team.
Early Systolic Dysfunction Following Traumatic Brain Injury: A Cohort Study
Authors: Krishnamoorthy Vijay , Rowhani-Rahbar Ali , Gibbons Edward F. , Rivara Frederick P. , Temkin Nancy R. , Pontius Crystal , Luk Kevin , Graves Morgan , Lozier Danielle , Chaikittisilpa Nophanan , Kiatchai Taniga , Vavilala Monica S.
Published: April 2017

Objective:

Prior studies have suggested that traumatic brain injury may affect cardiac function. Our study aims were to determine the frequency, longitudinal course, and admission risk factors for systolic dysfunction in patients with moderate-severe traumatic brain injury.

Design:

Prospective cohort study.

Setting:

Level 1 trauma center.

Measurements:

Transthoracic echocardiogram within 1 day and over the first week after moderate-severe traumatic brain injury; transthoracic echocardiogram within 1 day after mild traumatic brain injury (comparison group).

Measurements and Main Results:

Systolic function was assessed by transthoracic echocardiogram, and systolic dysfunction was defined as fractional shortening less than 25%. Multivariable Poisson regression models examined admission risk factors for systolic dysfunction. Systolic function in 32 patients with isolated moderate-severe traumatic brain injury and 32 patients with isolated mild traumatic brain injury (comparison group) was assessed with transthoracic echocardiogram. Seven (22%) moderate-severe traumatic brain injury and 0 (0%) mild traumatic brain injury patients had systolic dysfunction within the first day after injury (p < 0.01). All patients with early systolic dysfunction recovered in 1 week. Younger age (relative risk, 0.87; 95% CI, 0.79–0.94; for 1 yr increase in age) and lower admission Glasgow Coma Scale score (relative risk, 0.34; 95% CI, 0.20–0.58; for one unit increase in Glasgow Coma Scale) were independently associated with the development of systolic dysfunction among moderate-severe traumatic brain injury patients.

Conclusions:

Early systolic dysfunction can occur in previously healthy patients with moderate-severe traumatic brain injury, and it is reversible over the first week of hospitalization. Younger age and lower admission Glasgow Coma Scale score are independently associated with the development of systolic dysfunction after moderate-severe traumatic brain injury.
Occupational exposures and genetic susceptibility to urinary tract cancers: a systematic review and meta-analysis
Authors: Stojanovic Jovana , Milovanovic Sonja , Pastorino Roberta , Iavicoli Ivo , Boccia Stefania
Published: April 2017

This study aims to summarize the current knowledge on the relationship between genetic polymorphisms, occupational exposures, and urinary tract cancers. We searched MEDLINE, ISI Web of science, and SCOPUS online databases for all articles published in English language up to September 2016. A meta-analysis was performed to provide summary estimates for the association between a certain genetic polymorphism, occupational exposure and bladder cancer (BC) or kidney cancer (KC), when appropriate. Fifteen studies on BC and six on KC were deemed eligible for the review. With regard to BC, an overall odds ratio (OR) of 2.07 [95% confidence interval (CI): 1.38–3.09] for those with GSTM1 and an OR of 2.07 (95% CI: 1.38–3.09) for those with GSTT1 null genotype were reported when exposed to polycyclic aromatic hydrocarbons (PAHs). NAT2 slow genotype carriers had an OR of 3.59 (95% CI: 2.62–4.93) for BC when exposed to aromatic amines and an OR of 2.07 (95% CI: 1.36–3.15) when exposed to PAHs. With regard to KC and pesticide exposure, the meta-analysis reported an OR of 4.38 (95% CI: 2.28–8.41) for GSTM1 present genotype, an OR of 2.59 (95% CI: 1.62–4.15) for GSTT1-present genotype and an OR of 6.51 (95% CI: 2.85–14.89) for combined effects of GSTM1 and GSTT1 active genotypes. This meta-analysis indicates a possible association between the variant genotypes of GSTM1, GSTT1, NAT2 and SULT1A1, occupational exposure to aromatic amines or PAHs, and development of BC. Our results suggest that polymorphisms in GSTM1 and GSTT1 genes could influence the risk for developing KC in individuals occupationally exposed to pesticides.
Histological Features of Methylene Blue–Induced Phototoxicity Administered in the Context of Parathyroid Surgery
Authors: Maguire Ciara A. , Sharma Anup , Alarcon Lida , Ffolkes Lorrette , Kurzepa Malgorzata , Ostlere Lucy , Samarasinghe Venura , Singh Manuraj
Published: April 2017

Methylene blue is a chromophore dye known for its photosensitizing properties. It is also administered intravenously as a tracer in parathyroid surgery to identify abnormal glands. We describe 2 cases of acute methylene blue–induced phototoxicity in patients who underwent parathyroidectomy. Both patients developed an acute vesiculopustular inflammatory rash on the anterior neck corresponding to the site exposed intraoperatively to overhanging surgical lights. One of the patients also developed a bulla on her finger at the site of attachment of the oxygen probe. Biopsies were taken from both patients at different time points. The histological findings included destruction of sebaceous glands and deposition of diastase-periodic acid-Schiff–positive hyaline material around dermal blood vessels. These features are similar to those seen in skin treated with photodynamic therapy and systemic photosensitivity disorders such as the porphyrias. The wavelengths of light emitted by the surgical lights and oxygen probe overlap with the absorption spectrum of methylene blue. This resulted in excitation of the systemically administered methylene blue at exposed sites, with resultant local tissue damage and a phototoxic reaction.
Hemosiderotic Juvenile Xanthogranuloma
Authors: Fernandez-Flores Angel , Nicklaus Ina , Browne Fiona , Colmenero Isabel
Published: April 2017

Juvenile xanthogranuloma is a non-Langerhans cell lesion mostly limited to the skin but occasionally presenting in extracutaneous locations or associated with systemic conditions. Lesions need to be distinguished mainly from dermatofibroma, xanthoma, Langerhans cell histiocytosis, or reticulohistiocytoma. Herein, we present a hemosiderotic variant of juvenile xanthogranuloma in a 12-year-old girl, which we have not found described in literature. The lesion presented at the back of the scalp as a slowly growing yellowish polypoid lesion showing occasional bleeding. The histopathological examination demonstrated a cellular infiltrate expanding the dermis, with a Grenz zone and with no remarkable changes in the overlying epidermis. The papule was made of mononucleated macrophages, many of which were xanthomatous. There were some Touton giant cells. The lesion was intermingled with a mild inflammatory infiltrate comprising lymphocytes, plasma cells, neutrophils, and some eosinophils. Many of the macrophages contained abundant cytoplasmic deposits of iron. The macrophages expressed CD68 and CD163, whereas they failed to express S100 protein, CD1a, and Langerin.
Rapid Homogeneous Immunoassay to Quantify Gemcitabine in Plasma for Therapeutic Drug Monitoring
Authors: Kozo Daniel , Ross Matt W. , Jarrah Justin , Barrett Michael , Harney Rebecca L. , Courtney Jodi B. , Baburina Irina , Holleran Julianne L. , Beumer Jan H. , Peters Godefridus J. , Honeywell Richard J. , Salamone Salvatore J.
Published: April 2017

Background:

Gemcitabine (2′,2′-difluoro-2′-deoxycytidine) is a nucleoside analog used as a single agent and in combination regimens for the treatment of a variety of solid tumors. Several studies have shown a relationship between gemcitabine peak plasma concentration (Cmax) and hematological toxicity. An immunoassay for gemcitabine in plasma was developed and validated to facilitate therapeutic drug monitoring (TDM) by providing an economical, robust method for automated chemistry analyzers.

Methods:

A monoclonal antibody was coated on nanoparticles to develop a homogenous agglutination inhibition assay. To prevent ex vivo degradation of gemcitabine in blood, tetrahydrouridine was used as a sample stabilizer. Validation was conducted for precision, recovery, cross-reactivity, and linearity on a Beckman Coulter AU480. Verification was performed on an AU5800 in a hospital laboratory. A method comparison was performed with (LC-MS/MS) liquid chromatography tandem mass spectrometry using clinical samples. Selectivity was demonstrated by testing cross-reactivity of the major metabolite, 2′,2′-difluorodeoxyuridine.

Results:

Coefficients of variation for repeatability and within-laboratory precision were <8%. The deviation between measured and assigned values was <3%. Linear range was from 0.40 to 33.02 μ/mL (1.5–125.5 μM). Correlation with validated LC-MS/MS methods was R2 = 0.977. The assay was specific for gemcitabine: there was no cross-reactivity to 2′,2′-difluorodeoxyuridine, chemotherapeutics, concomitant, or common medications tested. Tetrahydrouridine was packaged in single-use syringes. Gemcitabine stability in whole blood was extended to 8 hours (at room temperature) and in plasma to 8 days (2–8°C).

Conclusions:

The assay demonstrated the selectivity, test range, precision, and linearity to perform reliable measurements of gemcitabine in plasma. The addition of stabilizer improved the sample handling. Using general clinical chemistry analyzers, gemcitabine could be measured for TDM.
Rotavirus Vaccination and the Risk of Celiac Disease or Type 1 Diabetes in Finnish Children at Early Life
Authors: Vaarala Outi , Jokinen Jukka , Lahdenkari Mika , Leino Tuija
Published: April 2017

Background:

Rotavirus infection has been suggested as a trigger of type 1 diabetes (T1D)-related autoimmunity and celiac disease (CD)-related autoimmunity.

Methods:

We carried out a nationwide, population-based cohort study evaluating whether prevention of rotavirus infection with vaccination affects the risk of CD and T1D diagnosed during 2009–2014 in Finnish children by comparing vaccinated and unvaccinated children in a cohort born in 2009–2010. Nationwide rotavirus vaccination records were collected from healthcare databases during 2009–2011 and validated for a sample of 495 children born from July 2009 to December 2009. Incident diagnoses of CD and T1D during 2009–2014 in the cohort were identified in the National Care Register.

Results:

The adjusted relative risks (with 95% confidence intervals) were 0.91 (0.69–1.20) for T1D and 0.87 (0.65–1.17) for CD in vaccinated children compared with unvaccinated, suggesting that oral rotavirus vaccination does not alter the risk of CD or T1D during 4–6 years follow-up after vaccination.

Conclusions:

Our results suggest that oral rotavirus vaccination is considered safe in the individuals at risk of CD and T1D.
Pneumococcal Immune Response in Infants Whose Mothers Received Tetanus, Diphtheria and Acellular Pertussis Vaccination During Pregnancy
Authors: Maertens Kirsten , Burbidge Polly , Van Damme Pierre , Goldblatt David , Leuridan Elke
Published: April 2017

Background:

Maternal immunization with a tetanus, diphtheria and acellular pertussis (Tdap) vaccine may blunt infant pneumococcal immune responses after a primary series of vaccines.

Methods:

As part of a prospective controlled cohort trial of Tdap (Boostrix; GSK Biologicals, Rixensart, Belgium) vaccination in pregnancy, infants born to vaccinated mothers and controls were immunized at 8 and 16 weeks and 12 months of age with 13-valent pneumococcal conjugate vaccine (Prevenar13; Pfizer, Wyeth, United States). Sera were tested for pneumococcal antibody concentrations against vaccine serotypes following primary and booster immunization.

Results:

Geometric mean concentration of antibodies to serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14 and 19A was significantly lower after 2 doses of Prevenar13 vaccine in the offspring of the mothers vaccinated in pregnancy. This blunting effect disappeared after a booster dose at 12 months of age, except for serotypes 1 and 4. Despite this blunting, the percentage of children achieving the threshold of protection of 0.35 µg/mL was comparable in the vaccine and the control group both after primary and booster vaccination with only a significant lower rate of seroprotection in the vaccine group for serotype 3 after primary vaccination. After booster vaccination, seroprotection rates increased further for serotypes 3, 5, 6B, 9V and 23F.

Conclusions:

The present results indicate a blunting effect after primary vaccination for some serotypes resolving after booster vaccination. Seroprotection rates were comparable both after primary and booster vaccination, except for serotype 3 with a significant lower seroprotection rate in the vaccine group after primary vaccination.