bluuebunny/crossref_metadata_2025 huggingface dataset:
Augmented External Fixation of Ulnar Carpometacarpal Joint Fracture Dislocations
Authors: Nishimura Reiji , Wright Lauren , Seitz William H.
Published: November 2018

Ulnar-sided carpometacarpal (CMC) joint fracture dislocations are relatively uncommon, frequently associated with fractures of the metacarpal base and/or hamate, and often sustained by young male individuals secondary to striking a hard object. The complexity of ulnar-sided CMC fracture dislocations necessitates careful restitution of anatomic alignment and joint congruency for mobility and stability. Miniaturization of the external fixation device has allowed application to the hand. Spanning external fixation utilizes the principles of “ligamentotaxis”—indirect reduction through distraction forces of capsule-ligamentous structures. Treatment options for ulnar-sided CMC fracture dislocations are varied. Our surgical technique involving an external fixation device is reviewed. Clinical and chart review was performed on the last 10 patients undergoing acute surgical repair of ulnar-sided CMC fracture dislocations with intra-articular comminution by the senior author. Surgical technique used percutaneous Kirschner wire fixation and a spanning, miniature, external fixation device. Minimal follow-up was 1 year. Radiographs from the most recent appointment were evaluated by 2 independent reviewers. Patients rated their level of pain and assessed function using a subjective outcome instrument. Mean total active motion, when comparing traumatized digit to same digit in contralateral hand, was 100%. All fractures healed primarily with maintenance of congruent joint space and without radiographic displacement or arthrosis. Patient satisfaction was high and all patients returned to preinjury level of function. Our study demonstrates the use of an external fixation device in the management of ulnar-sided CMC fracture dislocations to be effective in reestablishing and maintaining normal hand anatomy, reducing pain, increasing function, and preserving motion.
Loss of miR-155 upregulates WEE1 in metastatic melanoma
Authors: DiSano Julie A. , Huffnagle Ian , Gowda Raghavendra , Spiegelman Vladimir S. , Robertson Gavin P. , Pameijer Colette R.
Published: November 2018

Significant advances have been made in the treatment of melanoma by targeting key cellular pathways, but additional targets are needed as many patients do not respond or relapse with resistant disease. MicroRNA-155 (MiR-155) has previously been shown to regulate melanoma cell growth and acts as a tumor suppressor. We tested a clinical population of melanoma tumors for miR-155 expression, and find that expression is low in most patients, although not predictive of outcome. We identified the protein kinase WEE1 as a novel target of miR-155. A mouse model of experimental metastasis finds that both increased expression of miR-155 and silencing of WEE1 lead to decreased metastases. Loss of miR-155 and increased expression of WEE1 may contribute to the metastatic phenotype in patients with melanoma.
Nursing Considerations When Using Neuromuscular Blocking Agents to Assist With Intubation
Authors: Blauvelt Grant , Burdick Kailee , Cannon Emily J.
Published: November 2018

The use of neuromuscular blocking agents (NMBAs) in acute care settings during intubation is vitally important. The NMBAs increase first pass success rates significantly while protecting patients from gastric aspiration, tracheal injury, and death. During emergent intubations, succinylcholine and rocuronium are commonly used, but each comes with specific risks and individualized interventions. First pass success can be increased by ensuring correct dosing for overweight patients and employing the use of video laryngoscope. For planned, nonemergent intubations with sustained paralysis, the chosen NMBA can be individualized to fit the patient's needs. This includes dosages based on upregulation or downregulation of acetylcholine as well as speed of administration to prevent histamine release. Nurses must provide specific care when managing the treatment in high-risk patient populations (coronary artery disease, hyperkalemia, renal failure, liver failure, and traumatic brain injuries) who may receive certain types of NMBAs. Finally, because of the wide range of adverse effects with these drugs, close assessments are essential to prevent complications.
Clinical Education to Decrease Perceived Barriers to Delirium Screening in Adult Intensive Care Units
Authors: Fowler Brittany M.
Published: November 2018

Despite current advances in critical care medicine, delirium remains a frequent complication of an intensive care unit stay. The consequences can be severe and far reaching, including an increase in mortality, length of stay, and long-term cognitive sequelae. Frequently, delirium can be missed by clinicians who fail to complete a standardized delirium screening tool and, therefore, many cases go unrecognized and untreated. A multidimensional education program is one of the most effective methods to increase awareness of the condition and increase compliance in utilizing standardized delirium screening tools at the bedside.
Case Study Investigation Decreases Burnout While Improving Interprofessional Teamwork, Nurse Satisfaction, and Patient Safety
Authors: Hellyar Mary , Madani Catherina , Yeaman Sarah , O'Connor Kelly , Kerr Kim M. , Davidson Judy E.
Published: November 2018

Prevention of burnout is a national imperative, and blame-free investigations of clinical events are advocated. Reflective inquiry techniques are helpful in processing adverse events while minimizing blame. The purpose of this project was to develop an interprofessional peer review program (Case Study Investigation) to process emotions, improve teamwork, and optimize patient outcomes. This evidence-based practice project was conducted in a 12-bed intensive care unit using reflective inquiry techniques to perform peer case review across disciplines. Significant improvements were seen in percent strongly agree to the 2 satisfaction questions asked: “I feel free to speak up regarding issues that may affect patient care” (increased from 37% to 73%, χ2 = 6.19, P < .05), and “There is open communication between physicians and nurses” (rose from 33% to 73%, χ2 = 7.53, P < .05). In total, 95% perceived improvement in interprofessional teamwork. Burnout decreased significantly at 6 months (n = 22, M = 18.40, SD = 3.36) from baseline scores (n = 27, M = 21.96, SD = 4.47), F
2,72 = 4.48, P < .02. Central line–associated infections decreased from 3.6 per 1000 to 0 per 1000 catheter-days. Catheter-related urinary tract infections decreased from 2 per 1000 to 0 per 1000 patient-days. Both were sustained below benchmark. Reflective inquiry decreases nurse burnout while improving perceived interprofessional teamwork and employee satisfaction, and measurements of patient safety.
A Fully Automated Method for the Determination of Serum Belatacept and Its Application in a Pharmacokinetic Investigation in Renal Transplant Recipients
Authors: Klaasen Rolf Anton , Egeland Erlend Johannessen , Chan Joe , Midtvedt Karsten , Svensson My , Bolstad Nils , Fellström Bengt , Holdaas Hallvard , Åsberg Anders , Bergan Stein , Vethe Nils Tore , Warren David John
Published: November 2018

Background:

Belatacept (Nulojix; Bristol-Myers Squibb, New York, NY) is a biological immunosuppressive drug used for the prophylaxis of acute rejection after renal transplantation. Few studies have described belatacept pharmacokinetics, and the effect of therapeutic drug monitoring has not been investigated. We have developed a drug-capture assay (using drug target) to measure belatacept in serum and applied this assay in a pharmacokinetic study in renal transplant recipients.

Methods:

CD80 was used to trap belatacept onto streptavidin-coated wells. Captured drug was quantified using Eu3+-labeled protein A and time-resolved fluorescence. The assay was applied in a pilot pharmacokinetic study in renal transplanted patients receiving belatacept infusions. Belatacept serum concentrations were determined at several time points between belatacept infusions. A simple population pharmacokinetic model was developed to visualize measured and predicted belatacept serum concentrations.

Results:

The assay range was 0.9–30 mg/L with accuracy within 91%–99% and coefficients of variation ranging from 1.2% to 3.6%. Predilution extended the measurement range to 130 mg/L with an accuracy of 90% and coefficients of variation of 3.8%. Samples were stable during storage at 4°C for 15 days and during 2 freeze-thaw cycles. Belatacept concentrations were determined in a total of 203 serum samples collected during 26 infusion intervals from 5 renal transplant recipients. The population pharmacokinetic model visualized both measured and predicted concentrations.

Conclusions:

We have developed an automated, accurate, and precise assay for the determination of belatacept serum concentrations. The assay was successfully applied in a pharmacokinetic study in renal transplant recipients receiving belatacept infusions.
Malignant Glaucoma After Laser Peripheral Iridotomy
Authors: Greenfield Jason A. , Smiddy William E. , Greenfield David S.
Published: November 2018

Purpose:

We describe a patient with primary angle-closure glaucoma who developed malignant glaucoma following laser peripheral iridotomy.

Methods:

A 58-year-old male presented with peripheral and central anterior chamber shallowing following an uncomplicated Nd: YAG laser peripheral iridotomy. Intraocular pressure (IOP) and B-scan echography were normal, and there was −1.5 Ddiopter asymmetric myopia. Despite treatment with aqueous suppression and cycloplegia for 7 months, the patient developed progressive myopic shift and anterior chamber shallowing.

Results:

The patient underwent 23-G pars plana vitrectomy and lensectomy using a standard 3-port technique, and sulcus posterior chamber intraocular lens implantation in the left eye. Twelve months postoperatively, the anterior chamber has remained deep, best-corrected visual acuity is 20/15, and the IOP is 11 mm Hg.

Conclusions:

Malignant glaucoma is a rare complication of laser iridotomy and should be considered in eyes with progressive anterior chamber shallowing and myopia despite normal IOP.
Recurrent Exposure of XEN Gel Stent Implant and Conjunctival Erosion
Authors: Arnould Louis , Theillac Vincent , Moran Sarah , Gatinel Damien , Grise-Dulac Alice
Published: November 2018

Purpose:

The purpose of this study was to report a case of recurrent conjunctival erosion and XEN Gel Stent exposure after implantation in a primary open-angle glaucoma patient. Minimally invasive glaucoma surgery (MIGS) is a new approach in glaucoma surgery, and there is a lack of published data with regard to the management of postoperative ocular surface complications.

Methods:

This is a case report of a patient with a persistent corneal erosion after XEN Gel Stent implantation. A standalone MIGS surgery was planned for both eyes in this case of refractory glaucoma. Despite a first surgical revision, the patient was suffering from a chronic leaking bleb, an exposed XEN Gel Stent, and severe hypotonia in the left eye.

Results:

A free conjunctival autografting technique covered with a complementary amniotic membrane graft was performed under local anesthesia. One month following bleb revision, the intraocular pressure was 13 mm Hg on medical treatment, and slit-lamp examination showed a well-formed moderate bleb with no leakage.

Conclusions:

This is the first described case of the use of a free conjunctival autograft to treat a persistently leaking bleb after XEN Gel Stent implantation. This case highlights the potential complication of conjunctival erosion due to XEN Gel Stent implantation. It emphasizes the management of complicated filtration blebs after MIGS surgery.
Clinicopathologic Examination of Translucent Refractile Intraluminal Tissue Coagulum From the Proximal Tube of a Baerveldt Glaucoma Drainage Device
Authors: Lee Graham A. , Seo Shiney , Quagliotto Gary , Shah Peter
Published: November 2018

Purpose:

To describe an unusual case of glaucoma drainage tube blockage.

Patients:

A 76-year-old woman presented with left endothelial graft failure. Her previous ocular history included primary open-angle glaucoma diagnosed for 15 years and Fuch’s endothelial dystrophy. Three years before presentation, the left eye required a Descemet stripping endothelial keratoplasty followed by a trabeculectomy with mitomycin C and subsequent Baerveldt tube insertion 3 years previously. Intraocular pressures were right 9 and left 19 mm Hg. The endothelial graft demonstrated supra-temporal edema, in proximity to the sulcus placed tube tip.

Methods:

A repeat endothelial keratoplasty was undertaken. During surgery, an attempt to flush the tube ab internally with balanced salt solution on a 27-G Rycroft cannula, resulted in extrusion of a long translucent tubular plug from within the silicone tube into the anterior chamber. This was removed with intraocular forceps and sent for histopathology. The endothelial keratoplasty was performed and an air bubble placed in the anterior chamber.

Results:

The histopathology was reported as fibrinohemorrhagic material associated with refractile material, detected under polarized light microscopy. At 6 months follow-up, the graft was clearing well, the tube in situ and the intraocular pressure 6 mm Hg.

Conclusions:

One possible cause of the refractile material within the specimen is spalled particles of silicone, presumably from the tube. This finding potentially questions the long-term stability of silicone products in the eye and may be a cause of capsular fibrosis around the glaucoma drainage device plate.
Obesity increases the risk of chronic pain development after motor vehicle collision
Authors: Mauck Matthew C. , Hu JunMei , Sefton Christopher , Swor Robert A. , Peak David A. , Jones Jeffrey S. , Rathlev Niels K. , Lee David C. , Domeier Robert M. , Hendry Phyllis L. , McLean Samuel A.
Published: November 2018

Obesity has been found to increase the risk of musculoskeletal pain (MSP) in other settings, but to our knowledge, the influence of increased body mass index on pain outcomes after common trauma exposures such as motor vehicle collision (MVC) has not been assessed. In addition, obesity results in biomechanical changes, as well as physiologic changes including reduced hypothalamic pituitary adrenal axis negative feedback inhibition, but mechanisms by which obesity may result in worse post-traumatic outcomes remain poorly understood. In this study, we evaluated the influence of body mass index on axial and overall MSP severity (0-10 numeric rating scale) 6 weeks, 6 months, and 1 year after MVC among 917 European Americans who presented to the emergency department for initial evaluation. After adjusting for an array of sociodemographic factors, obesity (particularly morbid obesity) was an independent risk factor for worse MSP after MVC (eg, RR 1.41 [95% CI 1.11, 1.80] for moderate or severe MSP 6 months after MVC among morbidly obese vs normal weight MVC survivors). Interestingly, substantial effect modification was observed between obesity risk and a genetic variant known to reduce hypothalamic pituitary adrenal axis negative feedback inhibition (FKBP5 rs9380526). (eg, 41% vs 16% increased risk of moderate or severe MSP at 6 months among obese individuals with and without the risk allele.) Further studies are needed to elucidate mechanisms underlying chronic pain development in obese trauma survivors and to develop interventions that will reduce chronic pain severity among this common, at-risk group.
Pioglitazone, a PPARγ agonist, reduces cisplatin-evoked neuropathic pain by protecting against oxidative stress
Authors: Khasabova Iryna A. , Khasabov Sergey G. , Olson Julie K. , Uhelski Megan L. , Kim Amy H. , Albino-Ramírez Alejandra M. , Wagner Chad L. , Seybold Virginia S. , Simone Donald A.
Published: November 2018

Painful peripheral neuropathy is a dose-limiting side effect of cisplatin treatment. Using a murine model of cisplatin-induced hyperalgesia, we determined whether a PPARγ synthetic agonist, pioglitazone, attenuated the development of neuropathic pain and identified underlying mechanisms. Cisplatin produced mechanical and cold hyperalgesia and decreased electrical thresholds of Aδ and C fibers, which were attenuated by coadministration of pioglitazone (10 mg/kg, intraperitoneally [i.p.]) with cisplatin. Antihyperalgesic effects of pioglitazone were blocked by the PPARγ antagonist T0070907 (10 mg/kg, i.p.). We hypothesized that the ability of pioglitazone to reduce the accumulation of reactive oxygen species (ROS) in dorsal root ganglion (DRG) neurons contributed to its antihyperalgesic activity. Effects of cisplatin and pioglitazone on somatosensory neurons were studied on dissociated mouse DRG neurons after 24 hours in vitro. Incubation of DRG neurons with cisplatin (13 µM) for 24 hours increased the occurrence of depolarization-evoked calcium transients, and these were normalized by coincubation with pioglitazone (10 µM). Oxidative stress in DRG neurons was considered a significant contributor to cisplatin-evoked hyperalgesia because a ROS scavenger attenuated hyperalgesia and normalized the evoked calcium responses when cotreated with cisplatin. Pioglitazone increased the expression and activity of ROS-reducing enzymes in DRG and normalized cisplatin-evoked changes in oxidative stress and labeling of mitochondria with the dye MitoTracker Deep Red, indicating that the antihyperalgesic effects of pioglitazone were attributed to its antioxidant properties in DRG neurons. These data demonstrate clear benefits of broadening the use of the antidiabetic drug pioglitazone, or other PPARγ agonists, to minimize the development of cisplatin-induced painful neuropathy.
Cortical integration of bilateral nociceptive signals: when more is less
Authors: Northon Stéphane , Rustamov Nabi , Piché Mathieu
Published: November 2018

Integration of nociceptive information is essential to produce adapted responses, to promote body integrity and survival. However, how the brain integrates nociceptive inputs from different body areas remains unknown. The aim of this study was to examine the cortical integration of bilateral nociceptive inputs evoked by laser heat stimuli. Sixteen healthy volunteers (8 F, 8 M; age: 25.5 ± 4.3) were recruited to participate in one session during which painful laser stimuli were applied to their hands with 2 Nd:YAP laser systems. Electroencephalographic activity was recorded to measure laser-evoked potentials and event-related spectral perturbations. Twenty nociceptive stimuli were applied in each of the 4 counterbalanced conditions: (1) right hand, (2) left hand, and both hands with (3) attention to the right or (4) attention to the left. Compared with unilateral conditions, N2 and P2 peak amplitude as well as gamma oscillation power were decreased in bilateral conditions (P< 0.05), but these effects were not affected by the direction of attention (P> 0.1). By contrast, pain was not significantly different in any condition (P> 0.05). These findings show that although more nociceptive inputs reach the brain with multiple nociceptive stimuli, their sensory representation is decreased while pain perception remains unchanged. These interactions between cerebral processing of nociceptive information from different body regions could support coordinated behavioral responses when pain origins from multiple sources.
Does the clinical phenotype of mucolipidosis-IIIγ differ from its αβ counterpart?: supporting facts in a cohort of 18 patients
Authors: Nampoothiri Sheela , Elcioglu Nursel H. , Koca Suleyman S. , Yesodharan Dhanya , KK Chandrababu , Krishnan Vinod , Bhat Meenakshi , Mohandas Nair K  , Radhakrishnan Natasha , Kappanayil Mahesh , Sheth Jayesh J. , Alves Sandra , Coutinho Francisca , Friez Michael J. , Pauli Richard M. , Unger Sheila , Superti-Furga Andrea , Leroy Jules G. , Cathey Sara S.
Published: November 2018

Mucolipidosis-IIIγ (ML-IIIγ) is a recessively inherited slowly progressive skeletal dysplasia caused by mutations in GNPTG. We report the genetic and clinical findings in the largest cohort with ML-IIIγ so far: 18 affected individuals from 12 families including 12 patients from India, five from Turkey, and one from the USA. With consanguinity confirmed in eight of 12 families, molecular characterization showed that all affected patients had homozygous pathogenic GNPTG genotypes, underscoring the rarity of the disorder. Unlike ML-IIIαβ, which present with a broader spectrum of severity, the ML-III γ phenotype is milder, with onset in early school age, but nonetheless thus far considered phenotypically not differentiable from ML-IIIαβ. Evaluation of this cohort has yielded phenotypic findings including hypertrophy of the forearms and restricted supination as clues for ML-IIIγ, facilitating an earlier correct choice of genotype screening. Early identification of this disorder may help in offering a timely intervention for the relief of carpal tunnel syndrome, monitoring and surgery for cardiac valve involvement, and evaluation of the need for joint replacement. As this condition may be confused with rheumatoid arthritis, confirmation of diagnosis will prevent inappropriate use of immunosuppressants and disease-modifying agents.
Physical activity in adolescents and children and relationship to metabolic health
Authors: Whooten Rachel , Kerem Liya , Stanley Takara
Published: November 2018

Purpose of review

To summarize the recent developments relating to the role of physical activity in improving insulin resistance and metabolic syndrome in children and adolescents.

Recent findings

The current literature strengthens previous findings on the relationship between physical activity and metabolic health in children; suggests a protective role for physical activity in the setting of obesity; examines population-specific findings; addresses specific effects of different modalities of physical activity in improving health; reveals potential mediators in the relationship between physical activity and metabolic health; and suggests new markers of metabolic health that could potentially be used as outcomes in future physical activity studies.

Recent research generally confirms the role of physical activity in decreasing insulin resistance and metabolic syndrome in children and adolescents. However, the current literature is limited by unstandardized research methods and definitions, and also aggregation of different age groups, genders, and weight status. Future research should address these issues to offer targeted physical activity interventions.
Histopathologic analysis in the diagnosis and management of chronic rhinosinusitis
Authors: Shay Aryan D. , Tajudeen Bobby A.
Published: November 2018

Purpose of review

New research in the pathogenesis of chronic rhinosinusitis has shed light on an emerging classification system based on endotypes, which help to explain the individualized mechanism of disease in patients suffering from chronic rhinosinusitis with and without nasal polyps. The purpose of this review is to advocate the use of structured histopathologic analysis in the diagnosis and management of patients affected by chronic rhinosinusitis with and without polyps.

Recent findings

Numerous studies have demonstrated the role of inflammation in chronic rhinosinusitis and the ensuing histopatholgic changes. Few studies have implemented structured histopathologic analysis to guide diagnosis and treatment. Individualized therapy including biotherapeutics and comprehensive surgery has shown to improve outcomes in patients with refractory disease.

Structured histopathologic analysis can provide helpful information on the endotype of chronic rhinosinusitis. Routine use in clinical practice should be standardized especially in cases of chronic rhinosinusitis refractory to medical therapy and/or surgery.
Indications and endonasal treatment of petrous apex cholesterol granulomas
Authors: Kohanski Michael A. , Palmer James N. , Adappa Nithin D.
Published: November 2018

Purpose of review

Lesions of the petrous apex of the temporal bone can be challenging to access and approaches laterally through the mastoid as well as medially through an endonasal approach are utilized to access this region while preserving function of adjacent structures. Cholesterol granulomas of the petrous apex requiring surgery are marsupialized to prevent expansion of the inflamed cyst and relieve associated clinical symptoms. The endonasal approach to the petrous apex has in the past been limited to lesions medial to the internal carotid artery.

Recent findings

Endoscopic approaches have been developed to expand the range of petrous apex lesions that are accessible endonasally. These endonasal corridors include a nasopharyngeal/transclival corridor, lateralization of the internal carotid artery to create an expanded medial window, a pterygopalatine infrapetrosal approach, and a contralateral maxillary approach, which allow improved access to the inferior and lateral petrous apex. Nasoseptal flaps may reduce the risk of postoperative stenosis of the drainage tract.

Endoscopic endonasal approaches can be used safely to address both medial and lateral/inferior petrous apex lesions. Morbidity of these procedures is low and use of a nasoseptal flap may limit restenosis of the drainage pathway.
Measuring alloantibodies: a matter of quantity and quality
Authors: Kiernan Jeffrey J. , Ellison Cynthia A. , Tinckam Kathryn J.
Published: November 2018

Purpose of review

This review describes the utility and limitations of measure for assessing the presence, relative strength, and clinical impact of human leukocyte antigen (HLA) alloantibodies, as well as the other qualitative features of antibodies that are important considerations in assessing patient risk.

Recent findings

Using MFI as a measure of antibody amount is limited for a variety of reasons. Standardized serum manipulations such as ethylene-diamine-tetra-acetic acid treatment or serum dilution results in better definition of relationships between MFI and antibody titer or complement activation, toward greater alignment in defining positivity. Increased understanding of HLA epitopes has improved the ability to precisely define donor specific HLA antibody (DSA) specificities and the analysis of structural HLA Class II epitope mismatches in donor–recipient pairs may assist in the prevention of de novo DSA development. Studies of antibody isotypes and immunopathological mechanisms underlying graft injury mediated by non-HLA antibodies are expanding the assessemnt of immunological risk.

Careful analysis of both semiquantitative and qualitative properties of donor-specific antibodies continues to improve our ability to study the effects of DSA on clinical outcomes in solid organ transplantation.
Apolipoprotein L1 and kidney transplantation
Authors: Tedla Fasika M. , Yap Ernie
Published: November 2018

Purpose of review

Consistent associations between variants of the apolipoprotein L1 (APOL1) gene and nondiabetic nephropathy have been reported in individuals of African descent. Donor APOL1 genotype has also been linked to shorter renal allograft survival. This review summarizes recent advances in understanding the biology of APOL1 and their implications to kidney donors and recipients.

Recent findings

Approximately 12–13% of African Americans have two renal risk APOL1 variants but most do not develop kidney disease. Although the exact mechanisms linking APOL1 genotype to renal injury are not known, evidence from new experimental models suggests APOL1 mutations may accelerate age-related podocyte loss. Recent epidemiological studies indicate potential kidney donors with high-risk APOL1 variants have increased risk of chronic kidney disease (CKD) and donors with high-risk APOL1 variants have lower estimated glomerular filtration rate (eGFR) than those with low-risk variants. The absolute risk of CKD in otherwise healthy individuals carrying high-risk APOL1 mutations is likely low.

Recent studies suggest high-risk APOL1 mutations in kidney donors are linked to shorter graft survival and lower postdonation eGFR. APOL1 genotyping may be used as one of many factors that contribute to assessment of the risk of postdonation CKD and informed decision making.
Enteral Nutrition in Pediatric High-risk Head and Neck Cancer Patients Receiving Proton Therapy: Identifying Risk Factors and Quality of Life Concerns to Optimize Care
Authors: Bechtel Allison S. , Indelicato Daniel J. , Sandler Eric
Published: November 2018

Background:

Radiotherapy for pediatric head and neck tumors often results in mucositis and pain, limiting oral intake and compromising patients’ nutrition. There are little pediatric data available regarding enteral tube use and risk factors. Our objective was to estimate nutrition needs, identify risk factors contributing to nutritional decline and explore quality of life measures regarding enteral nutrition during proton radiotherapy.

Procedure:

Nutritional metrics and status were collected throughout radiation treatment for 32 patients. We surveyed patients/caregivers about their perceptions of enteral nutrition. Risk factors for progression to non–oral nutrition or >5% weight loss were evaluated using univariate analysis.

Results:

Patients who received any esophageal radiation or >30 Gy mean dose to the pharyngeal constrictors were more likely to experience >5% weight loss. These patients, as well as those who received a mean dose >30 Gy to the oropharynx or concurrent chemotherapy, were also more likely to require non–oral supplementation. Patients expressed the importance of maximizing nutrition and feared pain associated with a tube placement.

Conclusions:

Pediatric patients with head and neck cancer can be risk-stratified based on clinical and dosimetric factors. This data, combined with parent and patient perceptions, is key to the development of rational guidelines.
Glanzmann Thrombasthenia in Children: Experience From a Tertiary Care Center in Southern India
Authors: Kongalappa Smitha , Reddy Jyothi Muni , Durugappa Tarangini , D’Souza Fulton , Subramanian Sitalakshmi , Prakash Anand
Published: November 2018

Background:

Glanzmann thrombasthenia (GT) is a globally rare inherited disorder of hemostasis.

Objectives:

To describe the clinical profile of GT in a tertiary care center in Southern India.

Methods:

A retrospective chart review of all children with GT was performed between January 2005 and August 2017 in the Department of Paediatrics.

Results:

A total of 48 patients (representing 43 families) were included. Median age at diagnosis was 2.75 years (interquartile range: 1.5 to 6.75). Two thirds had an onset of bleeding within the first 2 years of life. Sixty-seven percent were born out of consanguineous marriage. The common symptoms were epistaxis, gingival bleeding, and ecchymoses. Neonatal onset of bleeding manifested as purpura, epistaxis, and intracranial hemorrhage. Postsurgical bleeding and menorrhagia were unique presentations in adolescence. About 25% had life-threatening hemorrhage while 50% had growth retardation due to chronic anemia.

Conclusions:

GT is relatively more common in areas of Southern India due to the higher prevalence of consanguinity. Chronic anemia can contribute to growth stunting in these patients.
Pulmonary Langerhans Cell Histiocytosis: A not so Benign Lesion
Authors: Halder Rohan , Anantharaman Meenakshi B. , Seth Tulika , Mahapatra Manoranjan , Saxena Renu
Published: November 2018

Langerhans cell histiocytosis is a multisystem disease affecting young children. Lung involvement has a myriad of manifestations and the outcomes for these patients have been poorly defined. We present a 2-year-old child who presented with multisystem disease with multiple lung cysts. Treatment consisted of multiagent chemotherapy for 18 months and was associated with a slow but favorable response.
Joint and soft-tissue injections in rehabilitation inpatients taking direct oral anticoagulants
Authors: Nord Hunter M. , Journeay W. Shane , Lipson David M.
Published: November 2018

The risk for complications associated with joint and soft-tissue injections in patients taking direct oral anticoagulants (DOACs) is not fully understood. In this retrospective evaluation of 445 inpatients in a rehabilitation hospital who received corticosteroid injections, complications were compared in patients on DOACs with those who were not. After a review of all injections, no adverse events of significant bleeding (intra-articular or extra-articular) were observed. These findings suggest no substantial increase in adverse events associated with the use of DOACs when performing joint and soft-tissue injection procedures in inpatient rehabilitation setting.
Cell Phone and Computer Use Among Parents Visiting an Urban Pediatric Emergency Department
Authors: Shields Wendy C. , Omaki Elise , McDonald Eileen M. , Rosenberg Ruth , Aitken Mary , Stevens Martha Wood , Gielen Andrea C.
Published: November 2018

Objectives

The objectives of this study were to estimate the prevalence of cell phone and computer use among urban families bringing their children to an emergency department and to determine which technologies parents prefer to use to receive health information.

Methods

We visited 2 pediatric emergency departments in Baltimore, Md, and Little Rock, Ark. A convenience sample of parents of children 8 years old or younger completed a self-administered survey in the waiting area.

Results

Two hundred thirty-eight surveys were completed. Respondents were primarily female (83%), less than 35 years old (74%), and had at least a high school diploma or General Educational Development (94%). Forty-three percent were employed full time. A majority (95%) of respondents reported owning a cell phone, with most (88%) owning a smartphone and 96% reported having some internet access. Of cell phone owners, 91% reported daily text messaging activity. Over half (63%) of respondents reported having computer internet access at home; 31% reported having internet access at work. Patterns of behavior and preferences emerged for both cell phone and computer use. Respondents were more likely to check their email (75% vs 50%, P < 0.0001) and access the internet (78% vs 67%, P = 0.002) with a smartphone rather than their computer.

Conclusions

Both cell phones and computers are prevalent and used among urban families seen in pediatric emergency departments, offering new ways to deliver health information to these often underserved populations. Providers aiming to deliver health information should consider smartphone applications, text message–based programs, and email to communicate with their patients.
CDC's Lead Poisoning Prevention Program: A Long-standing Responsibility and Commitment to Protect Children From Lead Exposure
Authors: Ettinger Adrienne S. , Leonard Monica L. , Mason Jacquelyn
Published: November 2018

The Centers for Disease Control and Prevention's (CDC's) Childhood Lead Poisoning Prevention Program (CLPPP) serves as the nation's public health leader and resource on strategies, policies, and practices aimed at preventing lead exposure in young children. CDC supports and advises state and local public health agencies and works with other federal agencies and partners to achieve the Healthy People 2020 objective of eliminating childhood lead exposure as a public health concern. Primary prevention—the removal of lead hazards from the environment before a child is exposed—is the most effective way to ensure that children do not experience the harmful effects of lead exposure. Blood lead screening tests and secondary prevention remain an essential safety net for children who may be exposed to lead. CDC's key programmatic strategy is to strengthen blood lead surveillance by supporting state and local programs to improve blood lead screening test rates, identify high-risk populations, and ensure effective follow-up for children with elevated blood lead levels. Surveillance plays a central role in helping measure the collective progress of federal, state, and local public health agencies in protecting children from lead, as well as enhancing our ability to target population-based interventions for primary prevention to those areas at highest risk. The CDC CLPPP has been at the front line of efforts to protect children from lead exposure and the resulting adverse health effects over the last 3 decades. As we chart our path for the future, we will continue to learn from past successes and challenges, incorporate new evidence and lessons learned, and work closely with federal, state, local, and nonprofit partners, experts in academia, and the community to advance the overarching goal of eliminating lead exposure in children.
The Flint Water Crisis: A Coordinated Public Health Emergency Response and Recovery Initiative
Authors: Ruckart Perri Zeitz , Ettinger Adrienne S. , Hanna-Attisha Mona , Jones Nicole , Davis Stephanie I. , Breysse Patrick N.
Published: November 2018

Context:

The City of Flint was already distressed because of decades of financial decline when an estimated 140 000 individuals were exposed to lead and other contaminants in drinking water. In April 2014, Flint's drinking water source was changed from Great Lakes' Lake Huron (which was provided by the Detroit Water and Sewerage Department) to the Flint River without necessary corrosion control treatment to prevent lead release from pipes and plumbing. Lead exposure can damage children's brains and nervous systems, lead to slow growth and development, and result in learning, behavior, hearing, and speech problems. After the involvement of concerned residents and independent researchers, Flint was reconnected to the Detroit water system on October 16, 2015. A federal emergency was declared in January 2016.

Program:

The Centers for Disease Control and Prevention provided assistance and support for response and recovery efforts including coordinating effective health messaging; assessing lead exposure; providing guidance on blood lead screening protocols; and identifying and linking community members to appropriate follow-up services.

In response to the crisis in Flint, Congress funded the Centers for Disease Control and Prevention to establish a federal advisory committee; enhance Childhood Lead Poisoning Prevention Program activities; and support a voluntary Flint lead exposure registry. The registry, funded through a grant to Michigan State University, is designed to identify eligible participants and ensure robust registry data; monitor health, child development, service utilization, and ongoing lead exposure; improve service delivery to lead-exposed individuals; and coordinate with other community and federally funded programs in Flint. The registry is also collaborating to make Flint “lead-free” and to share best practices with other communities.

Discussion:

The Flint water crisis highlights the need for improved risk communication strategies, and environmental health infrastructure, enhanced surveillance, and primary prevention to identify and respond to environmental threats to the public's health. Collecting data is important to facilitate action and decision making to prevent lead poisoning. Partnerships can help guide innovative strategies for primary lead prevention, raise awareness, extend outreach and communication efforts, and promote a shared sense of ownership.
Emerging concepts in HIV-associated cryptococcal meningitis
Authors: Lawrence David S. , Boyer-Chammard Timothée , Jarvis Joseph N.
Published: November 2018

Purpose of review

HIV-associated cryptococcal meningitis remains a significant contributor to AIDS-related mortality despite widened access to antiretroviral therapy. Even in clinical trial settings 10-week mortality is roughly 40%. A number of important clinical trials have either recently concluded or are actively recruiting.

Recent findings

Global burden of disease estimates suggest cryptococcal meningitis causes 181 100 deaths annually. Screening blood for cryptococcal antigen in HIV-infected individuals with CD4 cell counts less than 100 cells/μl and preemptive antifungal treatment for those with detectable cryptococcal antigen reduces the incidence of cryptococcal meningitis and is likely to reduce mortality. Cryptococcal meningitis treatment with conventional 14-day courses of amphotericin are associated with high toxicity and mortality and can be reduced to 7 days if given alongside flucytosine. Flucytosine is a significantly superior adjunct to amphotericin treatment compared with fluconazole. In settings without amphotericin B dual oral antifungal combinations of flucytosine and fluconazole offer an effective alternative treatment. A single, high-dose of liposomal amphotericin is effective at reducing fungal burden and is being tested in a phase III trial.

Recently completed and ongoing clinical trials are increasing our understanding of how to optimize induction therapy for cryptococcal meningitis. Advocacy efforts are needed to broaden access to amphotericin formulations and flucytosine.
The lived experience of breathlessness for people diagnosed with heart failure: a qualitative synthesis of the literature
Authors: Walthall Helen , Floegel Theresa
Published: November 2018

Purpose of review

The experience of breathlessness in patients with heart failure is understudied. This review was aimed at evaluating the most recent qualitative findings regarding the experience of breathlessness in persons diagnosed with heart failure.

Recent findings

A literature search was conducted using Pubmed, Psycinfo, BNI, Cinahl and Google Scholar including studies on breathlessness experience in patients with heart failure, published between 2017 and 2018. Only three studies were identified, and findings were categorized into five themes: acknowledgment of breathlessness, prevailing consequences of breathlessness, breathlessness in daily life, recognising when breathlessness is a problem and communicating breathlessness. Understanding the experience of breathlessness was different before and after heart failure diagnosis. Patients experienced similar physical and emotional consequences of breathlessness but varied in strategies to manage the symptom. Patients often do not report breathlessness symptom, or are not asked to describe their symptom by the provider.

Recent studies show those at risk for and those who have heart failure need appropriate education to recognize breathlessness as a critical symptom. In addition, adequate communication between patients and providers of the breathlessness symptom is needed to support management.
Structural heart disease: one valve does not fit all
Authors: German Konstantin S. , Kalra Ankur
Published: November 2018

Purpose of review

Highlight the difficulties patients, physicians, and the global economy face in relation to treatment of structural heart diseases. It is easy to be carried away by the excitement of medical advancement; however, it is difficult to demonstrate restraint. Transcatheter aortic valve replacement (TAVR) is a modern marvel that can help many patients when utilized appropriately. This article highlights the work that has been done to facilitate decision-making in this challenging patient population.

Recent findings

Patient selection is of paramount importance as TAVR remains a costly intervention. Currently, our gold standards for preprocedural patient evaluation are inadequate. Apropos, several objective tools are being developed to help clinicians evaluate frailty. Giving patients a more accurate postprocedure prognosis allows them to make informed decisions on whether this intervention is appropriate for their respective goals.

In order for us to fully embrace shared decision-making and cost-effectiveness, we must continue to work on our prognostic tools and have honest conversations with patients and their families to formulate individualized treatment plans. This becomes even more important when factors like economic impact of intervention are considered. In an era where cost-effective care has garnered more attention than ever before, we must do our best to make sure our interventions are in line with patient goals and offer the maximum amount of benefit, given the current cost of TAVR.
Accurate action potential inference from a calcium sensor protein through biophysical modeling:
Authors: Greenberg David S , Wallace Damian J , Voit Kay-Michael , Wuertenberger Silvia , Czubayko Uwe , Monsees Arne , Handa Takashi , Vogelstein Joshua T , Seifert Reinhard , Groemping Yvonne , Kerr Jason ND
Published: November 2018

Multiphoton imaging of genetically encoded calcium indicators is routinely used to report activity from populations of spatially resolved neurons in vivo. However, since the relationship between fluorescence and action potentials (APs) is nonlinear and varies over neurons, quantitatively inferring AP discharge is problematic. To address this we developed a biophysical model of calcium binding kinetics for the indicator GCaMP6s that accurately describes AP-evoked fluorescence changes in vivo. The model's physical interpretation allowed the same parameters to describe GCaMP6s binding kinetics for both in vitro binding assays and in vivo imaging. Using this model, we developed an algorithm to infer APs from fluorescence and measured its accuracy with cell-attached electrical recordings. This approach consistently inferred more accurate AP counts and times than alternative methods for firing rates from 0 to >20 Hz, while requiring less training data. These results demonstrate the utility of quantitative, biophysically grounded models for complex biological data.
A lipid-free and insulin-supplemented medium supportsde novofatty acid synthesis gene activation in melanoma cells
Authors: Wu Su , Näär Anders M.
Published: November 2018

While investigating the role played byde novolipid (DNL) biosynthesis in cancer cells, we sought a medium condition that would support cell proliferation without providing any serum lipids. Here we report that a defined serum free cell culture medium condition containing insulin, transferrin and selenium (ITS) supports controlled study of transcriptional regulation ofde novofatty acid (DNFA) production andde novocholesterol synthesis (DNCS) in melanoma cell lines. This lipid-free ITS medium is able to support continuous proliferation of several melanoma cell lines that utilize DNL to support their lipid requirements. We show that the ITS medium stimulates gene transcription in support of both DNFA and DNCS, specifically mediated by SREBP1/2 in melanoma cells. We further found that the ITS medium promoted SREBP1 nuclear localization and occupancy on DNFA gene promoters. Our data show clear utility of this serum and lipid-free medium for melanoma cancer cell culture and lipid-related areas of investigation.
Cell-free DNA Reveals Potential Zoonotic Reservoirs in Non-Human Primates
Authors: Kowarsky Mark , Vlaminck Iwijn De , Okamoto Jennifer , Neff Norma F , LeBreton Matthew , Nwobegabay Julius , Tamoufe Ubald , Ledoux Joseph Diffo , Tafon Babila , Kiyang John , Saylors Karen , Wolfe Nathan D , Quake Stephen R
Published: November 2018

The microbiome of non-human primates is relatively neglected compared with humans, and yet it is a source of many zoonotic diseases. We used high throughput sequencing of circulating cell-free DNA to identify the bacteria, archaea, eukaryotic parasites and viruses from over 200 individual non-human primates across 17 species from Africa. Many of the assembled sequences have low or no homology to previously sequenced microorganisms, while those that do have homology support prior observations of specific taxa present in primate microbiomes. The structure of the total microbiome is correlated with geographic location, even between distinct primate species which are co-located. However, we find that viruses have a particularly notable association with host taxa independent of geography. Numerous potentially zoonotic taxa were discovered in an unbiased manner, thereby expanding knowledge of host species diversity and strengthening the case for monitoring wildlife reservoirs.

One Sentence Summary

Blood from non-human primates provides insight into potential pathogens which might eventually infect humans.