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Purpose: Although mortality prediction tools are the subject of significant interest as components of comprehensive hip fracture protocols, few have been applied or validated to prospectively inform ongoing patient management. Five regional hospitals are currently generating real-time mortality risk scores for all adults at the time of admission using available laboratory and comorbidity data (Cowen et al. J Hosp Med 9(11):720–726, 2014). Although results for aggregated conditions have been published, the primary aim of this study is to determine how well prospectively calculated scores predict mortality for hip fracture patients specifically. Methods: Using a five-hospital database, 1376 patients who were prospectively scored on admission were identified from January 2013 to April 2017, cross-referencing ICD9/10 diagnosis and procedure codes for AO/OTA 31A1 through 31B3 fractures. Prospective mortality scores have been previously divided into 5 risk categories to facilitate ease of clinical use. Vital status was determined from hospital data, Social Security and Michigan Death Indices. Results: Prospective scores demonstrated good mortality prediction, with AUCs of 0.80, 0.73, 0.74 and 0.74 for in hospital, 30-, 60- and 90-day mortality, respectively. Patients in the top 2 mortality risk categories represented 30% (410/1376) of the cohort and accounted for 78% (25/32) of the inpatient and 59% (57/97) of the 30 day deaths. Conclusions: Implementation of this real-time mortality risk tool is feasible and valid for the prediction of short- to medium-term mortality risk for hip fracture patients, and potentially offers valuable information to guide ongoing patient management decisions such as admitting service or level of care. [ABSTRACT FROM AUTHOR]

Purpose: Existing literature is discrepant on the differences in blood loss and need for transfusion between short and long cephalomedullary nails used for extracapsular geriatric hip fractures. However, prior studies used the inaccurate estimated rather than the more accurate 'calculated' blood loss based on hematocrit dilution (Gibon in IO 37:735–739, 2013, Mercuriali in CMRO 13:465–478, 1996). This study sought to clarify whether use of short nails is associated with clinically meaningful reductions in calculated blood loss and resultant need for transfusion. Methods: A retrospective cohort study using bivariate and propensity score-weighted linear regression analyses was conducted examining 1442 geriatric (ages 60–105) patients undergoing cephalomedullary fixation of extracapsular hip fractures over 10 years at two trauma centers. Implant dimensions, pre and postoperative laboratory values, preoperative medications, and comorbidities were recorded. Two groups were compared based on nail length (greater or less than 235 mm). Results: Short nails were associated with a 26% reduction in calculated blood loss (95% confidence interval: 17–35%; p < 10–14) and a 24-min (36%) reduction in mean operative time (95% confidence interval: 21–26 min; p < 10–71). The absolute reduction in transfusion risk was 21% (95% confidence interval: 16–26%; p < 10–13) yielding a number needed to treat of 4.8 (95% confidence interval: 3.9–6.4) with short nails to prevent one transfusion. No difference in reoperation, periprosthetic fracture, or mortality was noted between groups. Conclusion: Use of short compared to long cephalomedullary nails for geriatric extracapsular hip fractures confers reduced blood loss, need for transfusion, and operative time without a difference in complications. [ABSTRACT FROM AUTHOR]

Background and objectives: The hallmark clinical manifestation of Huntington's disease (HD), namely lower weight and BMI has been reported in prodromal HD (PreHD) adults and also in PreHD children. Here, we aim to evaluate anthropometric measures of growth and development (height, weight, body mass index (BMI)) in a group of children, adolescents, and young adults diagnosed with Juvenile Onset Huntington's Disease (JHD). Methods: Growth measures for 18 JHD patients, documented prior to or shortly after diagnosis, were obtained through medical records. JHD growth measures were compared to a large sample (n = 274) of healthy children, as well as the Center for Disease Control (CDC) growth norms. Results: After controlling for sex and age, the JHD subjects had no significant differences in height. However, they were an average of 10% lower than controls in weight and BMI. Using CDC norms, the JHD subjects had the same pattern of normal height but decrement in weight. Length of cytosine-adenine-guanine (CAG) repeat in the huntingtin gene was significantly correlated to measures of weight with longer CAG repeats being associated with more severe weight reduction. A subset of 4 subjects had measures that pre-dated onset of any symptom and were therefore prodromal JHD (preJHD). These subjects also had a significant decrement in BMI compared to CDC norms. Conclusions: Children with JHD have normal height, but significantly reduced weight and BMI, indicative of a specific deficit in body weight. As the preJHD subjects were also low in BMI, this suggests that these changes are directly due to the effect of the mutated gene on development, rather than symptom manifestation of the disease itself. Potential mechanisms of the weight decrement include energy deficiency due to mitochondrial dysfunction during development. [ABSTRACT FROM AUTHOR]

The cytokine milieu is critical for orchestration of lineage development towards effector T cell (Teff) or regulatory T cell (Treg) subsets implicated in the progression of cancer and autoimmune disease. Importantly, the fitness and survival of the Treg subset is dependent on the cytokines Interleukin-2 (IL-2) and transforming growth factor beta (TGF-β). The production of these cytokines is impaired in autoimmunity increasing the probability of Treg conversion to aggressive effector cells in a proinflammatory microenvironment. Therapy using soluble TGF-β and IL-2 administration is hindered by the cytokines' toxic pleiotropic effects and hence bioavailability to CD4 + T cell targets. Thus, there is a clear need for a strategy that rectifies the cytokine milieu in autoimmunity and inflammation leading to enhanced Treg stability, frequency and number. Here we show that inert biodegradable nanoparticles (NP) loaded with TGF-β and IL-2 and targeted to CD4 + cells can induce CD4 + Tregs in-vitro and expand their number in-vivo . The stability of induced Tregs with cytokine-loaded NP was enhanced leading to retention of their suppressive phenotype even in the presence of proinflammatory cytokines. Our results highlight the importance of a nanocarrier-based approach for stabilizing and expanding Tregs essential for cell-immunotherapy of inflammation and autoimmune disease. [ABSTRACT FROM AUTHOR]

Surgical fixation of distal femur fractures in geriatric patients is an evolving topic. Unlike hip fractures, treatment strategies for distal femur fractures are ill-defined and lack substantive high-quality evidence. With an increasing incidence and an association with significant morbidity and mortality, it is essential to understand existing treatment options and their supporting evidence. Current fixation methods include the use of either retrograde intramedullary nails, or plate and screw constructs. Due to the variability in fracture patterns, the unique anatomy of the distal femur, and the presence or absence or pre-existing implants, decision-making as to which method to use can be challenging. Recent literature has sought to describe the advantages and disadvantages of each, however, there is currently no consensus on a standard of care, and little randomized evidence is available that directly compares intramedullary nails with plating. Future randomized studies comparing intramedullary nails with plating constructs are necessary in order to develop a standard of care based on injury characteristics. [ABSTRACT FROM AUTHOR]

The parasocial interaction relationship development process was explored by applying principles of uncertainty reduction theory. Results suggested that parasocial relationship development follows a path from (a) social and task attraction to (b) parasocial interaction to (c) a sense of relationship importance. Length of exposure to the television character was not related to parasocial interaction in the path model. The study affirmed the contribution of interpersonal communication theories to understanding relationships people have with television personalities. Implications for future research were explored. [ABSTRACT FROM AUTHOR]

Background: Use of large clinical and administrative databases for orthopaedic research has increased exponentially. Each database represents unique patient populations and varies in their methodology of data acquisition, which makes it possible that similar research questions posed to different databases might result in answers that differ in important ways.Questions/purposes: (1) What are the differences in reported demographics, comorbidities, and complications for patients undergoing primary TKA among four databases commonly used in orthopaedic research? (2) How does the difference in reported complication rates vary depending on whether only inpatient data or 30-day postoperative data are analyzed?Methods: Patients who underwent primary TKA during 2010 to 2012 were identified within the National Surgical Quality Improvement Programs (NSQIP), the Nationwide Inpatient Sample (NIS), the Medicare Standard Analytic Files (MED), and the Humana Administrative Claims database (HAC). NSQIP is a clinical registry that captures both inpatient and outpatient events up to 30 days after surgery using clinical reviewers and strict definitions for each variable. The other databases are administrative claims databases with their comorbidity and adverse event data defined by diagnosis and procedure codes used for reimbursement. NIS is limited to inpatient data only, whereas HAC and MED also have outpatient data. The number of patients undergoing primary TKA from each database was 48,248 in HAC, 783,546 in MED, 393,050 in NIS, and 43,220 in NSQIP. NSQIP definitions for comorbidities and surgical complications were matched to corresponding International Classification of Diseases, 9 Revision/Current Procedural Terminology codes and these coding algorithms were used to query NIS, MED, and HAC. Age, sex, comorbidities, and inpatient versus 30-day postoperative complications were compared across the four databases. Given the large sample sizes, statistical significance was often detected for small, clinically unimportant differences; thus, the focus of comparisons was whether the difference reached an absolute difference of twofold to signify an important clinical difference.Results: Although there was a higher proportion of males in NIS and NSQIP and patients in NIS were younger, the difference was slight and well below our predefined threshold for a clinically important difference. There was variation in the prevalence of comorbidities and rates of postoperative complications among databases. The prevalence of chronic obstructive pulmonary disease (COPD) and coagulopathy in HAC and MED was more than twice that in NIS and NSQIP (relative risk [RR] for COPD: MED versus NIS 3.1, MED versus NSQIP 4.5, HAC versus NIS 3.6, HAC versus NSQIP 5.3; RR for coagulopathy: MED versus NIS 3.9, MED versus NSQIP 3.1, HAC versus NIS 3.3, HAC versus NSQIP 2.7; p < 0.001 for all comparisons). NSQIP had more than twice the obesity as NIS (RR 0.35). Rates of stroke within 30 days of TKA had more than a twofold difference among all databases (p < 0.001). HAC had more than twice the rates of 30-day complications at all endpoints compared with NSQIP and more than twice the 30-day infections as MED. A comparison of inpatient and 30-day complications rates demonstrated more than twice the amount of wound infections and deep vein thromboses is captured when data are analyzed out to 30 days after TKA (p < 0.001 for all comparisons).Conclusions: When evaluating research utilizing large databases, one must pay particular attention to the type of database used (administrative claims, clinical registry, or other kinds of databases), time period included, definitions utilized for specific variables, and the population captured to ensure it is best suited for the specific research question. Furthermore, with the advent of bundled payments, policymakers must meticulously consider the data sources used to ensure the data analytics match historical sources.Level Of Evidence: Level III, therapeutic study. [ABSTRACT FROM AUTHOR]

Background: The insufficient understanding of unintended biological impacts from nanomaterials (NMs) represents a serious impediment to their use for scientific, technological, and medical applications. While previous studies have focused on understanding nanotoxicity effects mostly resulting from cellular internalization, recent work indicates that NMs may interfere with transmembrane transport mechanisms, hence enabling contributions to nanotoxicity by affecting key biological activities dependent on transmembrane transport. In this line of inquiry, we investigated the effects of charged nanoparticles (NPs) on the transport properties of lysenin, a pore-forming toxin that shares fundamental features with ion channels such as regulation and high transport rate. Results: The macroscopic conductance of lysenin channels greatly diminished in the presence of cationic ZnO NPs. The inhibitory effects were asymmetrical relative to the direction of the electric field and addition site, suggesting electrostatic interactions between ZnO NPs and a binding site. Similar changes in the macroscopic conductance were observed when lysenin channels were reconstituted in neutral lipid membranes, implicating protein-NP interactions as the major contributor to the reduced transport capabilities. In contrast, no inhibitory effects were observed in the presence of anionic SnO2 NPs. Additionally, we demonstrate that inhibition of ion transport is not due to the dissolution of ZnO NPs and subsequent interactions of zinc ions with lysenin channels. Conclusion: We conclude that electrostatic interactions between positively charged ZnO NPs and negative charges within the lysenin channels are responsible for the inhibitory effects on the transport of ions. These interactions point to a potential mechanism of cytotoxicity, which may not require NP internalization. [ABSTRACT FROM AUTHOR]

The increasing risk of incidental exposure to nanomaterials has led to mounting concerns regarding nanotoxicity. Zinc oxide nanoparticles (ZnO NPs) are produced in large quantities and have come under scrutiny due to their capacity to cause cytotoxicityin vitroand potential to cause harmin vivo.Recent evidence has indicated that ZnO NPs promote autophagy in cells; however, the signaling pathways and the role of ion release inducing toxicity remain unclear. In this study, we report that ZnO NPs are immunotoxic to primary and immortalized immune cells. Importantly, such immunotoxicity is observed in micein vivo, since death of splenocytes is seen after intranasal exposure to ZnO NPs. We determined that ZnO NPs release free Zn2+that can be taken up by immune cells, resulting in cell death. Inhibiting free Zn2+ions in solution with EDTA or their uptake with CaCl2abrogates ZnO NP-induced cell death. ZnO NP-mediated immune cell death was associated with increased levels of intracellular reactive oxygen species (ROS). ZnO NP death was not due to apoptosis, necroptosis or pyroptosis. Exposure of immune cells to ZnO NPs resulted in autophagic death and increased levels of LC3A, an essential component of autophagic vacuoles. Accordingly, ZnO NP-mediated upregulation of LC3A and induction of immune cell death were inhibited by blocking autophagy and ROS production. We conclude that release of Zn2+from ZnO NPs triggers the production of excessive intracellular ROS, resulting in autophagic death of immune cells. Our findings suggest that exposure to ZnO NPs has the potential to impact host immunity. [ABSTRACT FROM PUBLISHER]

Abstract: Activation of the genioglossus (GG) muscles is necessary to maintain the patency of the upper airway. In the condition of obstructive sleep apnea (OSA) this mechanism fails and the possible role of fatigue in its pathogenesis is still not fully understood. In this paper, a new electrode design for recording the genioglossus surface electromyogram (sEMG) is presented. The new design differs from a widely used GG surface electrode in both electrode configuration (unilateral rather than bilateral) and electrode material (Ag–AgCl rather than stainless steel (SS)). The separate effects of these factors were evaluated during force-varying and fatiguing contractions on normal human subjects and using GG sEMG model simulations. Unilateral sEMG was found to have lower amplitude, lower frequency content and a different rate of change of median frequency during fatiguing contractions. It was shown to overcome several disadvantages posed by the bilateral configuration and be more selective. Ag–AgCl has more favorable impedance characteristics and resulted in greater signal amplitudes. It was concluded that the new design is more suitable for detecting GG sEMG and allows more reliable interpretation of changes in sEMG due to physiological mechanisms, thus providing a new methodology for studying GG function and the role of fatigue in OSA. [Copyright &y& Elsevier]

Presents a case study of an agitated critically ill child treated with neuroleptic agent haloperidol. Clinical presentation of the patient; Medical treatment administered to the patient; Mechanism of action of haloperidol; Side effects of intravenous haloperidol.