bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of Cytochrome p450 and Soluble Epoxide Hydrolase Enzymes and Their Associated Metabolites in the Pathogenesis of Diabetic Cardiomyopathy
Authors: Maayah Zaid H. , McGinn Erica , Al Batran Rami , Gopal Keshav , Ussher John R. , El-Kadi Ayman O. S.
Published: July 2019

A plethora of studies have demonstrated that cardiomyopathy represents a serious source of morbidity and mortality in patients with diabetes. Yet, the underlying mechanisms of diabetic cardiomyopathy are still poorly understood. Of interest, cytochrome P450 2J (CYP2J) and soluble epoxide hydrolase (sEH) are known to control the maintenance of cardiovascular health through the regulation of cardioprotective epoxyeicosatrienoic acids (EETs) and its less active products, dihydroxyeicosatrienoic acids (DHETs). Therefore, we examined the role of the aforementioned pathway in the development of diabetic cardiomyopathy. Our diabetic model initiated cardiomyopathy as indexed by the increase in the expression of hypertrophic markers such asNPPA. Furthermore, diabetic cardiomyopathy was associated with a low level of cardiac EETs and an increase of the DHETs/EETs ratio both in vivo and in cardiac cells. The modulation in EETs and DHETs was attributed to the increase of sEH and the decrease of CYP2J. Interestingly, the reduction of sEH attenuates cardiotoxicity mediated by high glucose in cardiac cells. Mechanistically, the beneficial effect of sEH reduction might be due to the decrease of phosphorylated ERK1/2 and p38. Overall, the present work provides evidence that diabetes initiates cardiomyopathy through the increase in sEH, the reduction of CYP2J, and the decrease of cardioprotective EETs.
Chimeric Antigen Receptor T‐Cell Therapy Clinical Results in Pediatric and Young Adult B‐ALL
Authors: DiNofia Amanda M. , Maude Shannon L.
Published: July 2019

Chimeric antigen receptor (CAR)‐modified T‐cell therapy has revolutionized the care of patients with relapsed and refractory B‐cell acute lymphoblastic leukemia (B‐ALL). Results from clinical trials across multiple institutions report remarkable remission rates with CD19‐directed CAR‐modified T‐cell therapy. These remissions are also proving to be durable in many patients with a relapse‐free survival (RFS) of approximately 50% to 60% at 1 year across several trials and institutions in this population that has been historically very difficult to treat. In addition, new products are being developed to enhance upon the original CAR T‐cell products, which include a humanized CAR, allogeneic CARs, and both CD22 and biallelic CD19 and CD22 constructs. Toxicity after CAR‐modified T‐cell therapy is characterized by cytokine release syndrome (CRS) and neurotoxicity in the acute post‐infusion period and B‐cell aplasia as a long‐term consequence of treatment. This review will summarize the published data thus far on the use of CAR‐modified T‐cell therapy in pediatric B‐ALL and outline the various CAR products now being developed for this population. Delivery of this therapy and the decision to pursue hematopoietic stem cell transplant (HSCT) after treatment will be discussed.
Blue-Enriched White Light Therapy Reduces Fatigue in Survivors of Severe Traumatic Brain Injury: A Randomized Controlled Trial
Authors: Quera Salva Maria-Antonia , Azabou Eric , Hartley Sarah , Sauvagnac Rebecca , Leotard Antoine , Vaugier Isabelle , Pradat Diehl Pascale , Vallat-Azouvi Claire , Barbot Frederic , Azouvi Philippe
Published: July 2019

Objective:

Fatigue is one of the disabling sequelae of traumatic brain injury (TBI), with repercussions on quality of life, rehabilitation, and professional reintegration. Research is needed on effective interventions. We evaluated efficacy of blue-enriched white light (BWL) therapy on fatigue of patients with severe TBI.

Setting:

Physical Medicine and Rehabilitation and Physiology departments of University hospitals.

Participants:

Adult patients with fatigue symptoms following severe TBI, Fatigue Severity Scale (FSS) score 4 or more, Epworth Sleepiness Scale (ESS) score 10 or more, and/or Pittsburgh Sleep Quality Index (PSQI]) more than 5 were randomly assigned to one of 2 parallel groups: a BWL therapy group, with 30-minute exposure to waking white light enriched with blue for 4 weeks, and a group without light therapy (N-BWL), no light.

Design:

Randomized controlled trial. ClinicalTrials.gov number: NCT02420275.

Main Measures:

The primary outcome measure was the response of the FSS to 4 weeks of treatment. In addition, we assessed latency change of the P300 component of event-related potentials before and after therapy.

Results:

Significant improvement in the FSS score (P = .026) was found in the BWL group compared with the N-BWL group.

Conclusion:

BWL phototherapy reduces fatigue in patients with severe TBI.
Characterizing Comorbid Cerebrovascular Insults Among Patients With TBI at a TBI Model Systems Rehabilitation Center
Authors: Jenkins Randolph M. , Manche Nathaniel L. , Sima Adam P. , Marwitz Jennifer H. , Walker William C.
Published: July 2019

Objective:

Determine incidence and predictors of comorbid cerebrovascular injuries in patients with moderate to severe traumatic brain injury (TBI) and whether it influences rehabilitation outcomes.

Setting:

Inpatient Rehabilitation Facility (IRF) brain injury unit participating in NIDILRR TBI Model Systems (TBIMS).

Participants:

A total of 663 patients with moderate to severe TBI.

Design:

Observational study with prospective and retrospective data collection.

Main Measures:

New traumatic cerebral artery injury (TCAI) lesions of head/neck and new cerebral infarcts (CIs) abstracted from neuroimaging reports and clinical notes.

Results:

The incidence of comorbid CI was 8%, among whom 19% also had TCAI identified. The incidence of TCAI increased over time from 2% before 2008 to 10% after, probably from greater screening. Both CI and TCAI were associated with longer acute care stay. Cerebral infarct was also associated with longer posttraumatic amnesia and lower rate of functional gains.

Conclusions:

Using in-depth abstraction of imaging findings, the incidence of traumatic head/neck artery injuries, and CIs in patients with moderate to severe TBI were both higher than a recent TBIMS-wide study utilizing ICD coding. Cerebral infarct was associated with longer posttraumatic amnesia duration and slower functional gains. Further research is recommended on the outcome implications of concomitant cerebrovascular injury in patients with TBI.
Postdecisional Processing Delays in Metacognitive Monitoring After Traumatic Brain Injury
Authors: Chiou Kathy S. , Genova Helen M. , Lengenfelder Jean , Chiaravalloti Nancy D.
Published: July 2019

Objective:

To document the process by which metacognitive judgments (“online” monitoring of one's own cognitive performance during task completion) are made after traumatic brain injury (TBI).

Participants:

Sixteen community-dwelling adults with moderate to severe TBI and 16 matched healthy controls.

Design:

Prospective, cross-sectional design.

Measures:

Metacognitive retrospective confidence judgments and reaction times were collected as participants performed a metamemory task.

Results:

Adults with TBI did not differ from healthy peers in metacognitive accuracy; however, they took significantly longer to make retrospective confidence judgments. Retrospective confidence judgment reaction times were not consistently correlated to measures of processing speed in either sample.

Conclusions:

Adults with TBI engage in different postdecisional processes to make metacognitive judgments compared with healthy controls. Findings suggest that reaction times may be an important dimension of metacognition to assess clinically after TBI.
Respiratory Virus Epidemiology Among US Infants With Severe Bronchiolitis: Analysis of 2 Multicenter, Multiyear Cohort Studies
Authors: Hasegawa Kohei , Goto Tadahiro , Hirayama Atsushi , Laham Federico R. , Mansbach Jonathan M. , Piedra Pedro A. , Camargo Carlos A.
Published: July 2019

In 2 multicenter cohort studies of 2912 infants hospitalized for bronchiolitis during 2007–2014, the 5 most common pathogens were RSV (76.5%), rhinovirus (23.8%), coronavirus (6.9%), adenovirus (6.4%) and human metapneumovirus (6.0%). Hospitalization months significantly differed for these common pathogens (P ≤ 0.01), except for coronavirus (P = 0.30). There was a significant heterogeneity in temporal patterns by region in RSV-A and -B (both P < 0.001).
Clinical Presentation of Influenza in Children 6 to 35 Months of Age
Authors: Danier Jasur , Rivera Luis , Claeys Carine , Dbaibo Ghassan , Jain Varsha K. , Kosalaraksa Pope , Woo Wayne , Yanni Emad , Zaman Khalequ , Acosta Beatriz , Amanullah Arshad , Ariza Miguel , Arroba Basanta Maria L. , Bavdekar Ashish , Carmona Alfonso , Cousin Luis , Diaz Adolfo , Diez-Domingo Javier , Dinleyici Ener C. , Faust Saul N. , Garcia-Sicilia Jose , Gomez-Go Grace D. , Gonzales Maria L. A. , Hacimustafaoglu Mustafa , Hughes Stephen M. , Izu Allen , Jackowska Teresa , Kant Shashi , Lucero Marilla , Mares Bermudez Josep , Martinón-Torres Federico , Montellano May , Prymula Roman , Puthanakit Thanyawee , Ruzkova Renata , Sadowska-Krawczenko Iwona , Soni Jyoti , Szymanski Henryk , Ulied Angels , Schuind Anne , Innis Bruce L.
Published: July 2019

Background:

In an exploratory analysis of an inactivated quadrivalent influenza vaccine (IIV4) trial in children 6–35 months without risk factors for influenza, we evaluated clinical presentation of influenza illness and vaccine impact on health outcomes.

Methods:

This phase III trial was conducted in 13 geographically diverse countries across 5 influenza seasons (2011–2014). Children were randomized 1:1 to IIV4 or control. Active surveillance was performed for influenza-like episodes (ILE); influenza was confirmed by reverse transcription polymerase chain reaction (RT-PCR). The total vaccinated cohort was evaluated (N = 12,018).

Results:

5702 children experienced ≥1 ILE; 356 (IIV4 group) and 693 (control group) children had RT-PCR-confirmed influenza. Prevalence of ILE was similar in RT-PCR-positive and RT-PCR-negative cases regardless of vaccination. Breakthrough influenza illness was attenuated in children vaccinated with IIV4; moderate-to-severe illness was 41% less likely to be reported in the IIV4 group than the control group [crude odds ratio: 0.59 (95% confidence intervals: 0.44−0.77)]. Furthermore, fever >39°C was 46% less frequent following vaccination with IIV4 than with control [crude odds ratio: 0.54 (95% confidence intervals: 0.39−0.75)] in children with breakthrough illness. Health outcome analysis showed that, each year, IIV4 would prevent 54 influenza cases per 1000 children and 19 children would need to be vaccinated to prevent 1 new influenza case.

Conclusions:

In addition to preventing influenza in 50% of participants, IIV4 attenuated illness severity and disease burden in children who had a breakthrough influenza episode despite vaccination.
Safety and Efficacy of Ceftazidime-Avibactam Plus Metronidazole in the Treatment of Children ≥3 Months to <18 Years With Complicated Intra-Abdominal Infection: Results From a Phase 2, Randomized, Controlled Trial
Authors: Bradley John S. , Broadhurst Helen , Cheng Karen , Mendez Maria , Newell Paul , Prchlik Martin , Stone Gregory G. , Talley Angela K. , Tawadrous Margaret , Wajsbrot Dalia , Yates Katrina , Zuzova Antonina , Gardner Annie
Published: July 2019

Background:

Ceftazidime-avibactam plus metronidazole is effective in the treatment of complicated intra-abdominal infection (cIAI) in adults. This single-blind, randomized, multicenter, phase 2 study (NCT02475733) evaluated the safety, efficacy and pharmacokinetics of ceftazidime-avibactam plus metronidazole in children with cIAI.

Methods:

Hospitalized children (≥3 months to <18 years) with cIAI were randomized 3:1 to receive intravenous ceftazidime-avibactam plus metronidazole, or meropenem, for a minimum of 72 hours (9 doses), with optional switch to oral therapy thereafter for a total treatment duration of 7–15 days. Safety and tolerability were assessed throughout the study, along with clinical and microbiologic outcomes, and pharmacokinetics. A blinded observer determined adverse event (AE) causality, and clinical outcomes up to the late follow-up visit.

Results:

Eighty-three children were randomized and received study drug (61 ceftazidime-avibactam plus metronidazole and 22 meropenem); most (90.4%) had a diagnosis of appendicitis. Predominant Gram-negative baseline pathogens were Escherichia coli (79.7%) and Pseudomonas aeruginosa (33.3%); 2 E. coli isolates were ceftazidime-non-susceptible. AEs occurred in 52.5% and 59.1% of patients in the ceftazidime-avibactam plus metronidazole and meropenem groups, respectively. Serious AEs occurred in 8.2% and 4.5% of patients, respectively; none was considered drug related. No deaths occurred. Favorable clinical/microbiologic responses were observed in ≥90% of patients in both treatment groups at end-of-intravenous treatment and test-of-cure visits.

Conclusions:

Ceftazidime-avibactam plus metronidazole was well tolerated, with a safety profile similar to ceftazidime alone, and appeared effective in pediatric patients with cIAI due to Gram-negative pathogens, including ceftazidime-non-susceptible strains.
In the pursuit of partnership: patient and family engagement in critical care medicine
Authors: Farrier Christian E. , Stelfox Henry T. , Fiest Kirsten M.
Published: July 2019

Purpose of review

Patient and family partnership in critical care medicine research and clinical care is essential to achieve patient and family-centered care. Although there is an increasing interest in patient and family engagement, research is lacking to direct clinicians and researchers on how to provide opportunities for meaningful engagement. We review the recent literature and provide examples from our own experiences to guide all parties in this important and emerging area.

Recent findings

Though the literature is relatively nascent, studies suggest that there is a desire to engage patients and families in critical care medicine research and clinical care, however, uncertainty exists on how to achieve this goal. Engagement exists on a spectrum from presence to shared decision-making and direct contributions to care; most engagement in critical care medicine involves participation in research and presence at the bedside. Expectation management is essential for meaningful engagement and true partnership. Challenges to patient and family engagement exist, including determining appropriate compensation, aligning engagement with needs and skills, and recruitment, training and retention. These challenges can be mitigated with thoughtful planning and management.

Patient and family engagement in critical care medicine is an emerging field that requires further study to support definitive conclusions. Until then, it is important to match interested patients and family members with appropriate opportunities and provide training and support to ensure meaningful engagement.
Effect of chest compression on skeletal chest injuries: a retrospective study
Authors: Kim Hyung Il , Cha Kyoung-Chul , Chung Woo Jin , Noh Young Il , Kim Oh Hyun , Cha Yong Sung , Kim Hyun , Lee Kang Hyun , Kim Hye Sim , Hwang Sung Oh
Published: July 2019

Objective

Reports indicate that chest compression may induce skeletal chest injuries. We aimed to assess the factors associated with skeletal chest injuries and the probability of skeletal chest injuries following cardiopulmonary resuscitation (CPR) in patients who were successfully resuscitated after cardiac arrest.

Methods

This retrospective analysis used data from adult patients who were successfully resuscitated after cardiac arrest. Skeletal chest injuries were assessed by chest computed tomography images. Multiple logistic regression analysis was used to identify factors associated with skeletal chest injuries and a cubic spline was fitted to visualize the predicted probability of skeletal chest injuries.

Results

Among 274 patients (mean age: 62.6 years, 180 males), 185 (68%) had skeletal chest injuries. Patients with skeletal chest injuries were older in age (66.4 ± 12 vs 54.7 ± 17 years, P < 0.001), had a higher frequency of prehospital CPR (78.9 vs 66.3%, P = 0.024), and had a longer CPR duration (26.3 ± 19.4 vs 21.5 ± 14.8 minutes, P = 0.022). Multiple logistic regression analysis showed that age and CPR duration were associated with skeletal chest injuries [odds ratio (OR): 1.06, 95% confidence interval (CI): 1.04–1.08, P < 0.001 for age; OR: 1.03, 95% CI: 1.01–1.04, P = 0.006 for CPR duration). The probability of skeletal chest injuries was higher in patients over 60 years of age than those in patients under 60 years.

Conclusion

In our study, advanced age and CPR duration were factors associated with a greater risk of skeletal chest injuries in adult patients who were resuscitated after cardiac arrest.
Development and Implementation of a Model for Research, Evidence-Based Practice, Quality Improvement, and Innovation
Authors: Hagle Mary , Dwyer Darcy , Gettrust Lynn , Lusk Dana , Peterson Kristen , Tennies Sherry
Published: July 2019

Background:

Our medical center nursing council evaluated its current evidence-based practice (EBP) model and decided to consider alternatives.

Problem:

No models were inclusive of major nursing activities, such as EBP and quality improvement (QI) projects and research studies.

Approach:

A model was developed, meeting the criteria of accessibility, ease of use, and reflective of professional practice activities: EBP and QI projects, research studies, and innovation. In the new model, I3 Model for Advancing Quality Patient Centered Care, professional practice is represented by 3 “I's”: Inquiry, Improvement, and Innovation.

Outcomes:

The model provides an algorithm with steps and decision points for nurses to follow based on a question from a clinical issue or problem. The model was approved by nursing-shared governance and is used for guiding relevant projects.

Conclusion:

The I3 Model guides the nurse in inquiry or improvement while supporting a culture of innovation in professional practice.
Meaning of Courtesy and Respect
Authors: Mayfield Elizabeth , Highfield Martha E. F. , Mendelson Sherri
Published: July 2019

Background:

Treating patients with courtesy and respect has quality, ethical, and fiscal ramifications.

Purpose:

This qualitative study revealed meanings of nurse courtesy and respect as imbedded in nurse and patient stories.

Methods:

Audio-recorded interviews were collected from 15 registered nurses and 17 patients on a medical-surgical unit in a 377-bed, nonprofit, Magnet-recognized facility.

Results:

Six themes related to courtesy and respect emerged during descriptive content analysis by 2 researchers: (1) being attentive (with subthemes taking time, physical care, and proactive engagement); (2) giving empathetic support; (3) honoring culture and beliefs; (4) recognizing the family; (5) recognizing patient space; and (6) recognizing personhood (with subthemes of showing ordinary politeness and recognizing the individual and honoring choices).

Conclusions:

Informants' stories contributed toward a better understanding of what it means to treat patients with courtesy and respect; and they created context for interpreting HCAHPS (Hospital Consumer Assessment of Healthcare Providers and Systems) numerical results. Further research is warranted.
Implementing Clinical Practice Guidelines for Replacing Peripheral Intravenous Catheters
Authors: Oh Jong Hee , Shelly Mark , Nersinger Sharon , Cai Xueya , Olsan Tobie
Published: July 2019

Background:

A community hospital policy of routinely replacing peripheral intravenous catheters (PIVCs) needed updating to the clinical practice guideline (CPG) of clinically indicated replacement.

Methods:

Guided by Lean principles, a clinical nurse leader (CNL) led a quality improvement small test of change on a 38-bed medical unit. The impact of the CPG was evaluated using quality, safety, and workflow measures.

Results:

Nurses managed 469 inpatients, receiving 1033 PIVCs. Routine PIVC replacement declined from 34% to 3% (P < .001). PIVC dwell time ranged from 4 to 20 days and did not increase phlebitis (P = .41) or catheter-related bloodstream infections. Nurses attributed the improvements in workflow (P = .01) and the quality of patient care (94%) to the updated PIVC guideline.

Conclusions:

Clinically-indicated PIVC replacement reduced unnecessary catheter insertions, maintained patient safety, improved efficiency, and is being implemented hospital-wide. This project highlights and advances the CNL role in transforming healthcare.
Improving Sepsis Bundle Implementation Times
Authors: Threatt David L.
Published: July 2019

Background:

Early recognition of sepsis in the emergency room (ER) has been shown to improve treatment intervention times and decrease mortality.

Local Problem:

Failure to recognize early signs and symptoms of sepsis in the ER has led to poor sepsis bundle completion times.

Methods:

A comparison of preintervention and postintervention data was performed to determine whether sepsis bundle implementation times, mortality, and length of stay (LOS) improved.

Interventions:

An ER Nurse Sepsis Identification Tool, leadership buy-in from key stakeholders, and systemic inflammatory response syndrome (SIRS) education were implemented.

Results:

Postintervention, average bundle compliance time decreased 458 minutes (P < .001), average antibiotic administration time decreased 101 minutes (P < .001), overall sepsis mortality decreased 5.9% (P = .074), and there was no change to LOS.

Conclusions:

The implementation of an ER early sepsis identification tool, leadership buy-in, and SIRS education can lead to improved bundle implementation times in the ER.
Role of Melatonin in Breast Carcinoma: Correlation of Expression Patterns of Melatonin-1 Receptor With Estrogen, Progesterone, and HER2 Receptors
Authors: Goyal Ruchi , Gupta Tulika , Bal Amanjit , Sahni Daisy , Singh Gurpreet
Published: July 2019

Breast carcinoma is a multifaceted-etiology malignancy. The presence of estrogen (ER), progesterone (PR), and HER2 (human epidermal growth factor receptor 2) receptors in breast carcinoma tissue has therapeutic implications. Recent studies indicate that pineal hormone melatonin by its receptor melatonin 1 (MT1) also influences the development and growth of breast cancer cells. The aim of this cross-sectional study was to elucidate the expression pattern of MT1 receptor in relation to estrogen, progesterone, and HER2 receptors in breast carcinoma. Two groups (receptor positive and triple negative) of breast carcinoma were taken. For comparison, normal mammary tissue was used as control. Immunohistochemistry was carried out using anti-melatonin receptor 1A antibody. Membranous/cytoplasmic expression was seen more than the nuclear expression in the cancerous tissue. Positive correlation of the MT1 expression was seen with ER, PR, and HER 2 receptor. Higher MT1 receptor expression was seen in the receptor-positive cases in comparison with triple-negative cases, which might signify melatonin deficiency in the former, leading to reactive increase in cell receptors. No correlation of MT1 expression with Ki67 index or lymph node status in both receptor-positive and triple-negative cases was found. Normal mammary tissue mainly showed cytoplasmic MT1 immunoreactivity of epithelial cells (ducts and acini), myoepithelial cells, and lining epithelium of blood vessels. Receptor-positive cases would, therefore, benefit from the use of melatonin as supporting therapy. This indicates that melatonin receptor status can be used as an independent pathologic indicator to evaluate breast carcinoma tissue, and melatonin receptor status may help to determine treatment protocols.
Immunohistochemistry in the Postmortem Diagnosis of Sepsis: A Systematic Review
Authors: Barranco Rosario , Ventura Francesco
Published: July 2019

It is not uncommon for the forensic pathologist to question whether a deceased person had experienced sepsis that could have either been the cause of or contributed to the person’s death. Often, the missing typical pathologic factors or lack of clinical and circumstantial information on the death render the autopsy of a sepsis-related death a difficult task for the forensic pathologist. Several authors emphasize on how an immunohistochemical analysis could help in diagnosing death related to sepsis. The research we carried out analyzes the main scientific studies in the literature, primarily the tracing of 21 immunohistochemical antigens evaluated to help diagnose death related to sepsis. The purpose of this review was to analyze and summarize the markers studied until now and to consider the limitations of immunohistochemistry that currently exist with regard to this particular field of forensic pathology. Immunohistochemistry provided interesting and promising results, but further studies are needed in order for them to be confirmed, so that they may be applied in standard forensic practice.
Simplified Molecular Subtyping of Medulloblastoma for Reduced Cost and Improved Turnaround Time
Authors: Shuangshoti Somruetai , Tadadontip Paveen , Techavichit Piti , Thorner Paul S. , Shuangshoti Shanop , Teerapakpinyo Chinachote
Published: July 2019

Molecular subtyping of medulloblastoma (MB) has become increasingly important for prognosis and management. Typically this involves detailed molecular genetic testing which may not be available in all centers. The purpose of the present study was to find a simplified approach to assign molecular subtypes of MB for routine use in centers with more limited resources. The molecular subtypes of MBs from 32 Thai patients, aged 0.5 to 35 years, were first determined by NanoString. These results were then compared with those obtained using a combination of limited immunohistochemistry (IHC) (β-catenin, GAB-1, YAP-1, p75-NGFR, OTX2) and CTNNTB exon 3 mutation analysis. By NanoString assay, there were 6 MBs (19%) in the wingless (WNT) group, 8 (25%) in the sonic hedgehog (SHH) group, 7 (22%) in group 3, and 11 (34%) in group 4. Although β-catenin immunostaining missed 4/6 WNT MBs, CTNNTB mutation analysis confirmed all WNT MB cases with amplifiable DNA. The IHC panel correctly assigned all the other molecular subtypes, except for 1 MB in group 4. Thus, our protocol was able to correctly categorized 31/32 cases or 97% of cases. Our study is the first to report molecular subtypes of MB in Southeast Asia. We found that molecular subgroups of MBs can be reliably assigned using a limited IHC panel of β-catenin, GAB-1, YAP-1, p75-NGFR, OTX2, together with CTNNTB exon 3 mutation analysis. This simplified approach incurs lower cost and faster turnaround time compared with more elaborate molecular methodologies and should be beneficial to centers with reduced laboratory resources.
FDG-PET/CT Demonstrates Splenic Angiosarcoma Bone Marrow Metastasis
Authors: Takahashi Hiroaki , Hara Tadashi , Suzuki Hideo , Hashimoto Ryosuke , Minami Manabu
Published: July 2019

Some patients with splenic angiosarcoma initially manifest thrombocytopenia owing to hypersplenism or tumor-related bone marrow fibrosis. The diagnosis of bone marrow metastasis in patients with splenic angiosarcoma is challenging, as the presentation mimics idiopathic thrombocytopenic purpura or primary myelofibrosis. Our case showed diffuse FDG uptake in the vertebral bodies, sacroiliac bone, humerus, femur, and clavicles. It was pathologically diagnosed as bone marrow metastasis of splenic angiosarcoma. We believe that the heterogeneous FDG accumulation in the bone marrow, although nonspecific, can be useful for the diagnosis of the bone marrow metastasis in patients with splenic angiosarcoma.
Diffuse Infiltration of Multiple Myeloma With Initial Manifestation of Cavernous Sinus Syndrome Unveiled by 18F-FDG PET/CT
Authors: Li Chunyan , Shao Fuqiang , Yang Yuhui , Lan Xiaoli
Published: July 2019

Intracranial infiltration is a rare complication of multiple myeloma (MM), which is usually seen in advanced stage. Here, we report a 47-year-old woman with only cavernous sinus syndrome as first manifestation. Brain MR revealed cavernous sinus masses, leptomeningeal nodules, and osseous erosion, which were considered metastases. 18F-FDG PET/CT, which was further performed to identify potential primary lesions, showed increased uptake not only in cavernous sinus and leptomeninges but also in diffuse bone lesions, hepatic nodules, lymph nodes, subcutaneous nodules, and bilateral ovarian masses. Multiple myeloma with intracranial involvement was confirmed by biopsy and cerebrospinal fluid examination.
Detection of Uterine Leiomyosarcoma Peritoneal Lesions by SPECT/CT and ROLL Technique
Authors: Manca Gianpiero , Garau Ludovico Maria , Romanini Antonella , Rubello Domenico , Nuzzo Amedeo , Barbarello Linda , Fantechi Lorenzo , Colletti Patrick M. , Boggi Ugo , Volterrani Duccio
Published: July 2019

We reported the preoperative radio-guided localization of 4 peritoneal metastatic nodules in the case of a 45-year-old woman with uterine leiomyosarcoma. Three lines of chemotherapy were tried, but cardiotoxicity occurred. Within the context of so-called GOSTT (guided intraoperative scintigraphic tumor targeting), preoperative radio-guided localization of peritoneal metastases enabled their subsequent radio-guided excisional biopsy. SPECT/CT allowed for anatomical localization of the hot lesions and generated a 3-dimensional volume-rendering roadmap, facilitating a surgical approach.
Prognostic Value of Pretreatment Radiomic Features of 18F-FDG PET in Patients With Hodgkin Lymphoma
Authors: Lue Kun-Han , Wu Yi-Feng , Liu Shu-Hsin , Hsieh Tsung-Cheng , Chuang Keh-Shih , Lin Hsin-Hon , Chen Yu-Hung
Published: July 2019

Purpose

This study investigated whether a radiomic analysis of pretreatment 18F-FDG PET can predict prognosis in patients with Hodgkin lymphoma (HL).

Methods

Forty-two patients who were diagnosed as having HL and underwent pretreatment 18F-FDG PET scans were retrospectively enrolled. For each patient, we extracted 450 radiomic features from PET images. The prognostic significance of the clinical and radiomic features was assessed in relation to progression-free survival (PFS) and overall survival (OS). Receiver operating characteristic curve, Cox proportional hazards regression, and Kaplan-Meier analyses were performed to examine the potential independent predictors and to evaluate the predictive value.

Results

Intensity nonuniformity extracted from a gray-level run-length matrix and the Ann Arbor stage were independently associated with PFS (hazard ratio [HR] = 22.8, P < 0.001; HR = 7.6, P = 0.024) and OS (HR = 14.5, P = 0.012; HR = 8.5, P = 0.048), respectively. In addition, SUV kurtosis was an independent prognosticator for PFS (HR = 6.6, P = 0.026). We devised a prognostic scoring system based on these 3 risk predictors. The proposed scoring system further improved the risk stratification of the current staging classification (P < 0.001).

Conclusions

The radiomic feature intensity nonuniformity is an independent prognostic predictor of PFS and OS in patients with HL. We devised a prognostic scoring system, which may be more beneficial for patient risk stratification in guiding therapy compared with the current Ann Arbor staging system.
18F-FDOPA PET Compared With 123I-Metaiodobenzylguanidine Scintigraphy and 18F-FDG PET in Secreting Sporadic Pheochromocytoma
Authors: Lugat Alexandre , Drui Delphine , Mirallié Eric , Kraeber-Bodéré Françoise , Ansquer Catherine
Published: July 2019

We report the case of a 23-year-old man presenting a right hypersecreting pheochromocytoma, falsely negative on 18F-FDG PET/CT and on 123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy but strongly positive on 18F-FDOPA PET/CT. Functional imaging has a key role in diagnosis and prognosis of pheochromocytomas, but choosing the most relevant modality remains difficult. Despite its high specificity, 123I-MIBG has a limited sensitivity. 18F-FDG can be used, but it is an unspecific tracer, and 18F-FDG uptake in brown adipose tissue can hinder the analysis. However, 18F-FDOPA shows very high sensitivity and specificity in pheochromocytomas with fewer drug interferences than 123I-MIBG.
Pediatric Cervicofacial Actinomycosis: Lessons From a Craniofacial Unit
Authors: Glass Graeme E. , Staruch Robert M.T. , Bradshaw Karen , Charles Adrian K. , Stotland Mitchell A.
Published: July 2019

Actinomycosis is a rare disease that remains difficult to diagnose and manage. Prompted by 2 recent cases the authors sought evidence-based conclusions about best practice. A systematic review was conducted using standard PRISMA methodology. The study was registered prospectively (PROSPERO: CRD42018115064). Thirty-three children from 23 series are described. The mean age was 8 years (range 3–17). Fifty-five percent were female. Twenty cases involved bone (usually mandible); 13 cases involved cervicofacial soft tissue. Poor dental hygiene and oral trauma were implicated. The median diagnostic delay was 12 weeks (range 1–156 weeks). The median duration of definitive antibiotic therapy was 17 weeks (range 1–130 weeks). Although diagnostic delay did not correlate with number of surgeries, bony involvement was associated with more procedures (P 
= 0.008, unpaired t test). All (6) cases with residual infection had bony involvement (P 
= 0.06, Fisher exact test). Neither diagnostic delay nor number of surgeries significantly influenced infection-free outcome which, instead, relies on aggressive surgical debridement and prolonged antibiotic therapy. Mandibular involvement exhibits a higher surgical burden and chronicity in around a third of cases. As dental caries are implicated in mandibular disease, preventative strategies must focus on improving pediatric oral hygiene.
Factors Affecting Prognosis in Patients With Spontaneous Supratentorial Intracerebral Hemorrhage Under Medical and Surgical Treatment
Authors: Akpinar Elif , Gürbüz Mehmet Sabri , Berkman Mehmet Zafer
Published: July 2019

Spontaneous intracerebral hemorrhage (ICH) is a vascular brain disease that causes very high rates of death and disability. Whether surgical or medical treatment is more appropriate is controversial.

The purpose of the study was to examine the morbidity and mortality rates of surgical and medical therapy and their differences in order to determine which patients should be operated.

In our study, the authors selected randomly and evaluated retrospectively 49 patients who were operated in Haydarpaşa Numune Research and Education Hospital Neurosurgery Clinic and 51 patients who received medical therapy at Neurology Clinic for spontaneous supratentorial ICH between January 2007 and December 2011.

The authors documented a detailed history of each patient featuring their neurological examination, Glasgow Coma Scale (GCS), Modified Rankin Disability Scale (MRDS), imaging, age, gender, and history of stroke, hypertension, diabetes mellitus, smoking and alcohol use, aspirin, or coumadin usage.

As a result, the mortality rate found in our study was similar to previous studies (49%). Mortality of patients who underwent surgery (63%) found a higher rate of disability. This is because hematoma of the patients who were operated on larger volumes and diameters, GCS lower than and the higher MRDS scores, higher rates of herniation is connected. The authors concluded that very early operation does not create a difference in treatment between mortality rates. The authors observed that the most important factors for the prognosis of ICH patients whether operated or not are the GCS of patients at the time of arrival to the hospital and the nature of the hematoma.
Evaluation of Vestibular Bone Thickness in Class I Malocclusion Treatment With Corticotomy-Assisted Rapid Orthodontics
Authors: Gonen Zeynep Burcin , Alkan Alper , Ekizer Abdullah , Kutuk Nukhet , Tasdemir Zekeriya
Published: July 2019

Background:

Corticotomy-assisted rapid orthodontics is a widely used method for speeding up conventional orthodontics. This study (i) evaluates the effects of corticotomy alone, corticotomy combined with bone graft, and corticotomy with platelet-rich fibrin (PRF) on vestibular alveolar bone thickness in patients with class I malocclusion; (ii) compares the treatment time with a conventional orthodontic therapy group, and (iii) investigates the periodontal health of patients who have undergone corticotomy-assisted rapid orthodontics.

Methods:

The patients were divided into 3 groups: Group 1 (n = 10) underwent corticotomy alone; Group 2 (n = 10) underwent corticotomy combined with bone graft, and Group 3 (n = 10) underwent corticotomy combined with PRF. In the following stage, vestibular alveolar bone thicknesses were evaluated using 3-dimensional cone-beam computed tomography images.

Results:

The findings showed that Group 2 achieved a more significant augmentation of the vestibular alveolar bone than Groups 1 and 3 (P = 0.001, P = 0.003), while corticotomy-assisted rapid orthodontics decreased treatment times. Sufficient alveolar bone thickness and preservation of the periodontal health were achieved when the corticotomy procedure was either combined with a bone graft or with PRF in the Class-I malocclusion patients.

Conclusion:

Bone grafts provided better bone thickness at the buccal surface of the anterior teeth of the mandible and maxilla, whereas the thickness of the keratinized gingiva was better with PRF.
Comparison Effects of Platelet-Rich Fibrin on Macrofat and Shuffling Fat Grafting
Authors: Zhai Zhen , Yu Panxi , Huang Minlu , Jin Xiaolei , Yang Xiaonan , Qi Zuoliang
Published: July 2019

Fat acquisition, processing, and grafting techniques are considered to be the main factors affecting the volume retention rate of fat grafting. Shuffling fat (SF) is obtained by refining macrofat (MF), both of which have been applied in autologous fat grafting. However, few studies have focused on comparison effects of platelet-rich fibrin (PRF) on MF and SF grafting. Grafts were prepared by mixing MF and SF with PRF or normal saline at a ratio of 5:1, and grafted into symmetric recipient sites of a mouse's buttock. Grafts were harvested and analyzed at 4, 8, and 12 weeks. Groups containing PRF showed high volume retention rates and microcosmic evaluation scores at each time point compared with the control groups. Although without improved volume retention rate, group of SF containing PRF showed superior microcosmic evaluations compared with group of MF containing PRF. The results demonstrated that both the efficacy of MF and SF grafting can be enhanced by PRF, with even better quality of grafts for the SF grafting.
LncRNA-Ang362 Promotes Pulmonary Arterial Hypertension by Regulating miR-221 and miR-222
Authors: Wang Han , Qin Ruiling , Cheng Yanqin
Published: July 2019

Background:

Pulmonary arterial hypertension (PAH) is a life-threatening cardiopulmonary disorder. LncRNA-Ang362 (lnc-Ang362) regulates miR-221 and miR-222 in vascular smooth muscle cell proliferation, which can lead to PAH. The present study was designed to investigate the function and underlying mechanisms of lnc-Ang362 in PAH.

Methods:

The expression of lnc-Ang362, miR-221, and miR-222 in 15 PAH patients and 10 healthy controls was measured by qRT-PCR. Lnc-Ang362 overexpression vector and siRNA were transfected into human pulmonary arterial smooth muscle cells (HPASMCs), and cell proliferation, migration, and apoptosis rate were assessed. The protein expression of p-p65 and p-IκBα was measured by western blot. MiR-221 or miR-222 inhibitor was cotransfected with lnc-Ang362 overexpression vector into HPASMCs.

Results:

Data from the present study showed significantly increased lnc-Ang362, miR-221, and miR-222 expression in the lung tissues of patients with PAH and in hypoxic HPASMCs. Although overexpression of lnc-Ang362 promoted proliferation and migration of HPASMCs, inhibition of lnc-Ang362 had the opposite effect. In addition, apoptosis of HPASMCs significantly decreased after lnc-Ang362 overexpression and increased after lnc-Ang362 inhibition. Meanwhile, lnc-Ang362 upregulated miR-221 and miR-222 expression and activated the NFκB signaling pathway in HPASMCs. Moreover, miR-221 and the miR-222 inhibitor both attenuated the proliferation and migration effects of lnc-Ang362 and elevated apoptosis in these cells.

Conclusion:

Lnc-Ang362 played an important role in regulating the biological function of HPASMCs by promoting miR-221 and miR-222. Lnc-Ang362 thus may be a novel therapeutic lncRNA candidate for treating PAH.
Myofascial pain syndrome and trigger points: evaluation and treatment in patients with musculoskeletal pain
Authors: Barbero Marco , Schneebeli Alessandro , Koetsier Eva , Maino Paolo
Published: July 2019

Purpose of review

Myofascial pain syndrome is a chronic pain condition characterized by the presence of myofascial trigger point, a hyperirritable painful spot involving a limited number of muscle fibers. The literature suggest that myofascial trigger points should be considered peripheral pain generators and this critical review will summarize recent findings concerning the clinical evaluation and the treatment of myofascial trigger points.

Recent findings

The clinical features of myofascial trigger points and their contribution to the patient pain and disability have been detailed in several recent studies, which support the clinical relevance of the condition. Recent studies reported that manual palpation to identify MTrPs has good reliability, although some limitations are intrinsic to the diagnostic criteria. During the last decade, a plethora of treatments have been proposed and positive effects on pain and function demonstrated.

The myofascial trigger point phenomenon has good face validity and is clinically relevant. Clinicians are encouraged to consider the contribution of myofascial trigger points to the patient's pain and disability through a careful medical history and a specific manual examination. Patients with myofascial trigger points will benefit from a multimodal treatment plan including dry needling and manual therapy techniques. Internal and external validity of research within the field must be improved.
Neuropathies and paraproteins
Authors: Lunn Michael P.
Published: July 2019

Purpose of review

There is an increasingly recognized association between haematological and neurological disease. This is especially true in the peripheral nervous system in which, to an extent, proof of a link is easier to achieve. The most sensitive low level paraprotein detection methods should always be employed in which a paraprotein is suspected. Peripheral nerves can be damaged not only by the immunological targeting of the myelin by the paraprotein, but by deposition (light chain amyloid and cryoglobulins) or direct infiltration (neurolymphomatosis). This has resulted in other defined paraprotein-related disease pathogeneses.

Recent findings

Our opportunities for treating these patients are greater not only through better recognition of disease but also treatments introduced from haematological research. Beyond rituximab, combination therapies, proteasome inhibition and novel biological treatments are being described in haematological practice with early efficacy in neurology. Important developments here should be exploited in neurology to improve outcomes.

This review of the current literature focuses not only on the long-term outcome studies in anti-myelin-associated glycoprotein neuropathy, but developments in the diagnosis and treatment of monoclonal gammopathy of undetermined significance and Waldenström's Macroglobulinaemia.
New insights on the disease contribution of neuroinflammation in amyotrophic lateral sclerosis
Authors: Chiot Aude , Lobsiger Christian S. , Boillée Séverine
Published: July 2019

Purpose of review

Amyotrophic lateral sclerosis (ALS) is a degenerative motor neuron disease with a strong neuroinflammatory component. This review summarizes how the connection between neurodegeneration and the immune system is strengthened by new discoveries from ALS genetics and the analysis of subpopulations of immune cells in ALS.

Recent findings

Recent genes identified in ALS encode for proteins with direct immune roles, which when mutated lead to deregulation of immune functions, potentially influencing the disease. Although neuroinflammation in the central nervous system (CNS) of ALS patients has been well documented, new evidence suggests also direct malfunctions of immune cells in the CNS and at the periphery. Although CD4+ T-regulatory lymphocytes are protective in ALS, their number and function are altered over the disease course. CD8+ T cells are detrimental for motor neurons in the CNS but show some protective roles at the periphery. Similarly, the presence of mast cells in muscles of ALS models and patients and impairments of monocyte functions reveal potential new players in ALS disease progression.

Although motor neuron degeneration is considered the prime event in ALS, dysfunctions in immune processes can impact the disease, highlighting that targeting specific immune components is a strategy for developing biomarkers and ultimately new drugs.
Cerebrospinal Fluid Concentrations of Nimodipine Correlate With Long-term Outcome in Aneurysmal Subarachnoid Hemorrhage: Pilot Study
Authors: Riva Roberto , Pegoli Marianna , Contin Manuela , Perrone Alessandro , Mohamed Susan , Zanello Marco
Published: July 2019

Objectives

The aim was to evaluate plasma and cerebrospinal fluid (CSF) nimodipine concentrations in patients with aneurysmal subarachnoid hemorrhage and their correlation with clinical outcome.

Methods

Nimodipine infusion was started at 1 mg/h and increased up to 2 mg/h and continued up to 21 days in surviving patients. Arterial and CSF samples were collected at least after 24 hours of stable nimodipine dosing. Delayed cerebral ischemia and vasospasm were documented by new neurological deficits and neuroimaging. The clinical outcome was assessed at 9 months by the modified Rankin scale.

Results

Twenty-three patients were enrolled. Nimodipine dose was 13 to 38 μg/kg per hour. Nimodipine arterial and CSF concentrations were 24.9 to 71.8 ng/mL and 37 to 530 pg/mL, respectively. Dose did not correlate with arterial or CSF concentrations. Arterial concentrations did not correlate with corresponding CSF concentrations. Doses and arterial concentrations did not correlate with the clinical outcome and were not associated with the occurrence of delayed cerebral ischemia. However, patients with no significant disability after 9 months of hemorrhage showed significantly higher CSF nimodipine concentrations (P = 0.015) and CSF-to-plasma ratios (P = 0.011) compared with patients who showed some degree of disability or who died.

Conclusions

Cerebrospinal fluid nimodipine concentrations measured during hospital drug infusion showed a correlation with long-term clinical outcome in patients with aneurysmal subarachnoid hemorrhage. These very preliminary data suggest that CSF concentrations monitoring may have some value in managing these patients.