Outcomes of a Novel Spine Virtual Fracture Clinic in an Australian Tertiary Hospital.

STUDY DESIGN: This was a retrospective cohort study. OBJECTIVE: To determine the proportion of referrals diverted by the SVFC from traditional outpatient clinic management. SUMMARY OF BACKGROUND DATA: The consistent rise in demand for orthopaedic outpatient clinic services is creating marked challenges to the provision of quality care. Virtual fracture clinics for upper and lower limb fractures have reduced the burden on outpatient clinics through telephone-based management of these conditions. To date, no study describes the expansion of virtual care to the spine trauma population. METHODS: A study of spine fractures referred to the RMH Department of Orthopaedic Surgery was conducted comparing outcomes prior to (January to December 2021) and following (July 2022 to November 2023) implementation of a spine virtual fracture clinic (SVFC). The primary aim of this study was to investigate the effects of a telephone-based SVFC on outpatient clinic activity, represented by the proportion of referrals discharged without requiring in-person clinic review. Secondary aims included appointment utilisation, lost to follow-up rates, duration of care, missed or mis-diagnoses, unplanned operations and complications. RESULTS: A total of 91.9% (n=666) referrals managed by the SVFC were discharged without in-person clinic attendance. Compared to outpatient clinic management (n=150 referrals), SVFC implementation was associated with reductions in the average number of consultations per referral (1.8 versus 2.4, P<0.001), appointments not attended (5% versus 13%, P<0.001), referrals lost to follow-up (0 versus 10.7%, P<0.001) and a shorter duration of care (median 48 d versus 58 d, P<0.001). A total of 65 patients (8.1%) were redirected to in-person clinics of which three underwent surgical intervention. No diagnostic errors, complications or adverse events were identified. CONCLUSION: This study demonstrates that a SVFC is an effective and safe alternative pathway to traditional hospital-based outpatient clinics with low-risk for any adverse outcomes.

Paediatric hip ultrasound.

Aims: The aim of this study was to investigate the agreement in interpretation of the quality of the paediatric hip ultrasound examination, the reliability of geometric and morphological assessment, and the relationship between these measurements. Methods: Four investigators evaluated 60 hip ultrasounds and assessed their quality based the standard plane of Graf et al. They measured geometric parameters, described the morphology of the hip, and assigned the Graf grade of dysplasia. They analyzed one self-selected image and one randomly selected image from the ultrasound series, and repeated the process four weeks later. The intra- and interobserver agreement, and correlations between various parameters were analyzed. Results: In the assessment of quality, there a was moderate to substantial intraobserver agreement for each element investigated, but interobserver agreement was poor. Morphological features showed weak to moderate agreement across all parameters but improved to significant when responses were reduced. The geometric measurements showed nearly perfect agreement, and the relationship between them and the morphological features showed a dose response across all parameters with moderate to substantial correlations. There were strong correlations between geometric measurements. The Graf classification showed a fair to moderate interobserver agreement, and moderate to substantial intraobserver agreement. Conclusion: This investigation into the reliability of the interpretation of hip ultrasound scans identified the difficulties in defining what is a high-quality ultrasound. We confirmed that geometric measurements are reliably interpreted and may be useful as a further measurement of quality. Morphological features are generally poorly interpreted, but a simpler binary classification considerably improves agreement. As there is a clear dose response relationship between geometric and morphological measurements, the importance of morphology in the diagnosis of hip dysplasia should be questioned.

Establishing Institutional Scores With the Rigor and Transparency Index: Large-scale Analysis of Scientific Reporting Quality.

BACKGROUND: Improving rigor and transparency measures should lead to improvements in reproducibility across the scientific literature; however, the assessment of measures of transparency tends to be very difficult if performed manually. OBJECTIVE: This study addresses the enhancement of the Rigor and Transparency Index (RTI, version 2.0), which attempts to automatically assess the rigor and transparency of journals, institutions, and countries using manuscripts scored on criteria found in reproducibility guidelines (eg, Materials Design, Analysis, and Reporting checklist criteria). METHODS: The RTI tracks 27 entity types using natural language processing techniques such as Bidirectional Long Short-term Memory Conditional Random Field-based models and regular expressions; this allowed us to assess over 2 million papers accessed through PubMed Central. RESULTS: Between 1997 and 2020 (where data were readily available in our data set), rigor and transparency measures showed general improvement (RTI 2.29 to 4.13), suggesting that authors are taking the need for improved reporting seriously. The top-scoring journals in 2020 were the Journal of Neurochemistry (6.23), British Journal of Pharmacology (6.07), and Nature Neuroscience (5.93). We extracted the institution and country of origin from the author affiliations to expand our analysis beyond journals. Among institutions publishing >1000 papers in 2020 (in the PubMed Central open access set), Capital Medical University (4.75), Yonsei University (4.58), and University of Copenhagen (4.53) were the top performers in terms of RTI. In country-level performance, we found that Ethiopia and Norway consistently topped the RTI charts of countries with 100 or more papers per year. In addition, we tested our assumption that the RTI may serve as a reliable proxy for scientific replicability (ie, a high RTI represents papers containing sufficient information for replication efforts). Using work by the Reproducibility Project: Cancer Biology, we determined that replication papers (RTI 7.61, SD 0.78) scored significantly higher (P<.001) than the original papers (RTI 3.39, SD 1.12), which according to the project required additional information from authors to begin replication efforts. CONCLUSIONS: These results align with our view that RTI may serve as a reliable proxy for scientific replicability. Unfortunately, RTI measures for journals, institutions, and countries fall short of the replicated paper average. If we consider the RTI of these replication studies as a target for future manuscripts, more work will be needed to ensure that the average manuscript contains sufficient information for replication attempts.

Transfer of Salmonella from Inert Food Contact Surfaces to Wheat Flour, Cornmeal, and NaCl.

ABSTRACT: Salmonella contamination in a dry processing facility frequently requires removal methods that are nonaqueous. Removal of pathogens from food processing systems with a purge of uncontaminated dry food materials has been proposed; however, little is known with respect to efficacy. In this study, survival of Salmonella on inert contact surfaces and transfer of Salmonella from inert contact surfaces to low-moisture foods were evaluated. Six stainless steel and polymeric food contact material types, in bead form, were contaminated at 11 log CFU/mL and then stored at two temperatures, 25 and 4°C, for 6 months. Simultaneously, three dry food materials or ingredients were used to remove Salmonella from contaminated beads. Wheat flour, cornmeal, and NaCl (1 g each) were mechanically mixed with 3 beads of each material type. The rate of microbial transfer from contaminated beads to food materials was measured. Further experimentation using multiple transfers was applied on two representative beads types, 316 stainless steel and polypropylene, representing common surface contact materials used in processing equipment. Survival of Salmonella on beads depended on storage temperature, with longer survival (P < 0.05) at 4°C than at 25°C, but survival was not influenced by type of bead material. Transfer of Salmonella from stainless steel beads to flour was significantly greater (P < 0.05) than from plastic. Transfer rates from stainless steel to wheat flour, cornmeal, and NaCl were measured as -0.5713, -0.2592, and -1.4221 log CFU of Salmonella removed per cm2 per g of clean material used. Transfer rates from polypropylene to whole wheat flour, cornmeal, and NaCl were more than 10-fold lower at -0.0156, -0.0148, and -0.0129 log CFU of Salmonella removed per cm2 per g of clean material used. These results indicate that although material type may not influence Salmonella survival during storage, Salmonella is more easily removed from stainless steel than polypropylene.

Hierarchical clustering by patient-reported pain distribution alone identifies distinct chronic pain subgroups differing by pain intensity, quality, and clinical outcomes.

BACKGROUND: In clinical practice, the bodily distribution of chronic pain is often used in conjunction with other signs and symptoms to support a diagnosis or treatment plan. For example, the diagnosis of fibromyalgia involves tallying the areas of pain that a patient reports using a drawn body map. It remains unclear whether patterns of pain distribution independently inform aspects of the pain experience and influence patient outcomes. The objective of the current study was to evaluate the clinical relevance of patterns of pain distribution using an algorithmic approach agnostic to diagnosis or patient-reported facets of the pain experience. METHODS AND FINDINGS: A large cohort of patients (N = 21,658) completed pain body maps and a multi-dimensional pain assessment. Using hierarchical clustering of patients by body map selection alone, nine distinct subgroups emerged with different patterns of body region selection. Clinician review of cluster body maps recapitulated some clinically-relevant patterns of pain distribution, such as low back pain with radiation below the knee and widespread pain, as well as some unique patterns. Demographic and medical characteristics, pain intensity, pain impact, and neuropathic pain quality all varied significantly across cluster subgroups. Multivariate modeling demonstrated that cluster membership independently predicted pain intensity and neuropathic pain quality. In a subset of patients who completed 3-month follow-up questionnaires (N = 7,138), cluster membership independently predicted the likelihood of improvement in pain, physical function, and a positive overall impression of change related to multidisciplinary pain care. CONCLUSIONS: This study reports a novel method of grouping patients by pain distribution using an algorithmic approach. Pain distribution subgroup was significantly associated with differences in pain intensity, impact, and clinically relevant outcomes. In the future, algorithmic clustering by pain distribution may be an important facet in chronic pain biosignatures developed for the personalization of pain management.

Initial Clinical Experience Treating Patients With Lung Cancer on a 6MV-Flattening-Filter-Free O-Ring Linear Accelerator.

Introduction Modern technologies, like intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT), have improved the therapeutic ratio of thoracic radiotherapy (TRT) for lung cancer (LC). Halcyon™ (Varian Medical Systems, Palo Alto, CA, USA), a novel 6MV-flattening-filter-free O-ring linear accelerator (6X-FFF ORL), was designed to deliver IMRT and VMAT with greater speed than a C-arm linac. Herein, we report our initial clinical experience treating patients with LC on this linac. Methods All patients who received TRT for LC on the 6X-FFF ORL at our institution were retrospectively identified. Patients' clinicopathologic data, radiotherapy details, early disease-control and toxicity outcomes, dosimetric data, couch corrections, and treatment times are reported. Results Between 10/2018-12/2019, 30 consecutive patients (median age 66 years, range 54-94 years) received definitive or post-operative TRT for LC (median 66 Gy/33 fractions; range 5-70 Gy/2-37 fractions) following four-dimensional computed tomography (CT) simulation (97%) using daily kilovoltage KV cone-beam CT (CBCT) (100%) on a 6X-FFF ORL for non-small cell LC (84%) or small cell LC (16%), with 53% receiving VMAT, 43% receiving static-field IMRT, and 77% receiving concurrent systemic therapy. All plans were approved through institutional peer review. The average three-dimensional vector couch correction based on CBCT guidance was 0.90 ± 0.50 cm. The average beam-on and beam on plus CBCT times were 1.7 ± 1.1 min, and 5.0 ± 3.2 min, respectively. Grade 3 dyspnea and fatigue occurred in 3% and 3% of patients, respectively. There were no grade ≥4 toxicities. Conclusion In this first clinical report of TRT for LC on a 6X-FFF ORL, daily CBCT-guided treatment was fast and safe with respect to dosimetry and clinical outcomes. Thus, use of this linac for TRT may increase LC patient throughput without a detriment in radiotherapy quality.

A Multidisciplinary Consensus Recommendation on a Synoptic Radiation Treatment Summary: A Commission on Cancer Workgroup Report.

PURPOSE: The radiation treatment summary provides a clinical and technical overview of a patient's full course of radiation therapy. Despite its importance to multiple stakeholders, there is no widely followed radiation treatment summary template. METHODS AND MATERIALS: The Commission on Cancer convened a multistakeholder workgroup to develop a synoptic radiation treatment summary template. The workgroup included individuals with expertise in radiation, medical and surgical oncology, medical physics, oncology informatics, cancer registry, electronic medical record systems, treatment planning systems, and registry information systems. The workgroup iterated a template until consensus was achieved. RESULTS: The consensus radiation treatment summary template is divided into 3 sections that allows for a mix of structured and free text. The first section, "Radiation Course Summary," is meant to provide information that is of broad interest and in a manner that is potentially accessible to patients, their families, and nononcology-trained care team members. The second section, "Anatomic Target Summary," provides information that is potentially useful to oncology-trained care team members who will be primarily interested in which anatomies were irradiated, by what modality, and to what cumulative dose. The third section, "Delivered Prescriptions," summarizes technical information that is primarily of interest and accessible to radiation oncology-trained clinicians, registrars, and researchers. CONCLUSIONS: We have proposed a consensus template with 3 sections to meet the needs of a diverse set of consumers. We recommend that providers, professional societies, and accreditation bodies with interest in the radiation treatment summary continue collaborative efforts to test, iterate, and drive adoption of a synoptic template.

The effects of cryopreserved red blood cell transfusion on tissue oxygenation in obese trauma patients.

BACKGROUND: Low tissue oxygenation (StO2) is associated with poor outcomes in obese trauma patients. A novel treatment could be the transfusion of cryopreserved packed red blood cells (CPRBCs), which the in vitro biochemical profile favors red blood cell (RBC) function. We hypothesized that CPRBC transfusion improves StO2 in obese trauma patients. METHODS: Two hundred forty-three trauma patients at five Level I trauma centers who required RBC transfusion were randomized to receive one to two units of liquid packed RBCs (LPRBCs) or CPRBCs. Demographics, injury severity, StO2, outcomes, and biomarkers of RBC function were compared in nonobese (body mass index [BMI] < 30) and obese (BMI ≥ 30) patients. StO2 was also compared between obese patients with BMI of 30 to 34.9 and BMI ≥ 35. StO2 was normalized and expressed as % change after RBC transfusion. A p value less than 0.05 indicated significance. RESULTS: Patients with BMI less than 30 (n = 141) and BMI of 30 or greater (n = 102) had similar Injury Severity Score, Glasgow Coma Scale, and baseline StO2. Plasma levels of free hemoglobin, an index of RBC lysis, were lower in obese patients after CPRBC (125 [72-259] µg/mL) versus LPRBC transfusion (230 [178-388] µg/mL; p < 0.05). StO2 was similar in nonobese patients regardless of transfusion type, but improved in obese patients who received CPRBCs (104 ± 1%) versus LPRPCs (99 ± 1%, p < 0.05; 8 hours after transfusion). Subanalysis showed improved StO2 after CPRBC transfusion was specific to BMI of 35 or greater, starting 5 hours after transfusion (p < 0.05 vs. LPRBCs). CPRBCs did not improve clinical outcomes in either group. CONCLUSION: CPRBC transfusion is associated with increased StO2 and lower free hemoglobin levels in obese trauma patients, but did not improve clinical outcomes. Future studies are needed to determine if CPRBC transfusion in obese patients attenuates hemolysis to improve StO2. LEVEL OF EVIDENCE: Therapeutic, level IV.

Coxsackie Myocarditis and Hepatitis with Reactivated Epstein-Bar Virus (EBV): A Case Report.

BACKGROUND Myocarditis, defined as inflammation of myocardial tissue of the heart, is an uncommon cardiac presentation and is due to a variety of causes. It affects 1% of the US population, 50% of which is caused by coxsackie B virus. Cardiac tissue is the prime target, and destruction of myocardium results in cardiac failure with fluid overload. CASE REPORT Our patient was a 57-year-old woman with fever, headache, neck pain, and generalized malaise. Her white blood cell count was 13×10³ cells/mm³. Interestingly, lumbar puncture ruled out meningitis. An echocardiogram to evaluate elevated troponin revealed an ejection fraction of 30% with severe left ventricular global hypokinesis without valvular vegetations consistent with new-onset systolic heart failure. Cardiac MRI showed a small pericardial effusion with bilateral pleural effusion. As she continued to be febrile, a viral panel was ordered, revealing coxsackie B4 antibody titer of 1: 640 (reference: >1: 32 indicates recent infection) with positive Epstein-Barr virus deoxyribonucleic acid by PCR, consistent with viral myocarditis. CONCLUSIONS Coxsackie B virus myocarditis is rarely recognized and reported by the general internist in clinical practice, so we would like present our experience with an interesting clinical presentation of the viral prodrome. An estimated 95% people in the US are infected with Epstein-Barr virus by adulthood, but it remains dormant in memory B lymphocytes. Recirculation of these B cells in lymphoid tissue stimulated by antigens, which in our case is coxsackie B virus; they differentiate into plasma cells, and the production of Z Epstein-Barr replication activator protein (ZEBRA) increases viral replication, thus explaining the positive EBV DNA measured by PCR.

Discovery of Clinical Candidate CEP-37440, a Selective Inhibitor of Focal Adhesion Kinase (FAK) and Anaplastic Lymphoma Kinase (ALK).

Analogues structurally related to anaplastic lymphoma kinase (ALK) inhibitor 1 were optimized for metabolic stability. The results from this endeavor not only led to improved metabolic stability, pharmacokinetic parameters, and in vitro activity against clinically derived resistance mutations but also led to the incorporation of activity for focal adhesion kinase (FAK). FAK activation, via amplification and/or overexpression, is characteristic of multiple invasive solid tumors and metastasis. The discovery of the clinical stage, dual FAK/ALK inhibitor 27b, including details surrounding SAR, in vitro/in vivo pharmacology, and pharmacokinetics, is reported herein.

Impact of image guidance during whole-brain radiation therapy.

PURPOSE: Radiation oncologists are rapidly adopting image-guided radiation therapy (IGRT), warranting further evaluation of its role and value. We analyzed the impact of IGRT for one of the most common radiation treatments. METHODS AND MATERIALS: We retrospectively identified patients who received whole-brain radiation therapy (WBRT) with mask immobilization and who underwent routine IGRT with kilovoltage imaging. We calculated IGRT shifts by comparing couch positions before and after imaging. We determined the dosimetric impact of IGRT on lens maximum and dose received by 95% (D95%) of the brain and cribriform region. We calculated episode of care costs using the Medicare Physician Fee Schedule. RESULTS: A total of 206 patients received 2392 image-guided fractions. The median absolute shift was 1 mm, 1 mm, and 2 mm in the vertical, lateral, and longitudinal directions, respectively. Ninety-nine percent of shifts were ≤6 mm, 7 mm, and 9 mm in the vertical, lateral, and longitudinal directions, respectively. For the 22 patients with the largest average shift per fraction, treating without IGRT would have changed D95% brain by a median 3 cGy (interquartile range, 2-9) and D95% cribriform region by a median 39 cGy (interquartile range, 7-116). Without IGRT, lens doses would have increased for 11/22 patients and decreased for 11/22. Using a 700 cGy lens threshold, there was no net change in the proportion of patients above and below the threshold regardless of IGRT use. For a 10-fraction course, daily IGRT accounted for 10% of the total episode of care cost. CONCLUSIONS: IGRT results in small positional corrections during WBRT. Even among cases with the largest shifts, the dosimetric impact is minor for the brain and modest for the cribriform region and lenses. This study suggests mask immobilization alone is sufficient for routine cases, and it may help clinicians make evidence-based decisions about IGRT in this setting.

Effect of re-transfusion systems on physiotherapy participation and transfusion in total knee joint arthroplasty.

BACKGROUND: Total knee joint arthroplasty is associated with significant blood loss. We hypothesized that re-transfusion drains would be associated with a lesser requirement for allogeneic blood transfusion and result in earlier physiotherapy participation and decreased length of hospital stay. METHODS: We performed a retrospective analysis of 303 patients with a mean age of 68.3 years (44-91) who underwent unilateral primary total knee joint arthroplasty within a single orthopaedic unit. A re-transfusion drain, deep drain, superficial drain or no drain was placed at the time of surgery. Blood tests were taken pre- and post-operatively, and blood transfusions were given based on the haemoglobin and clinical symptoms. Medical records data were used to determine the day patients sat out of bed, mobilized more than 10 m and were discharged from hospital. RESULTS: Patients with a re-transfusion drain were able to sit out of bed (P = 0.006), mobilize more than 10 m (P = 0.006) and were ready for discharge earlier (P = 0.013) than those without a re-transfusion drain. The use of a re-transfusion drain showed no effect on allogenic blood transfusion requirement; however, it was associated with decreased haemoglobin drop when compared with other drain types (P = 0.003). CONCLUSION: Our results suggest that the use of a re-transfusion system following total knee arthroplasty has beneficial physiotherapy outcomes and a decreased length of stay.

Transfusion of cryopreserved packed red blood cells is safe and effective after trauma: a prospective randomized trial.

OBJECTIVES: To determine the safety and efficacy of cryopreserved packed red blood cell (CPRBC) transfusion in trauma patients. BACKGROUND: Liquid packed red blood cells (LPRBCs) have an abbreviated shelf-life and worsening storage lesion with age. CPRBCs are frozen 2 to 6 days after donation, stored up to 10 years, and are available for 14 days after thawing and washing. CPRBCs can be utilized in diverse settings, but the effect on clinical outcomes is unknown. METHODS: We performed a prospective, randomized, double-blind study at 5 level 1 trauma centers. Stable trauma patients requiring transfusion were randomized to young LPRBCs (≤14 storage days), old LPRBCs (>14 storage days), or CPRBCs. Tissue oxygenation (StO2), biochemical and inflammatory mediators were measured, and clinical outcomes were determined. RESULTS: Two hundred fifty-six patients with well-matched injury severity and demographics (P > 0.2) were randomized (84 young, 86 old, and 86 CPRBCs). Pretransfusion and final hematocrits were similar (P > 0.68). Patients in all groups received the same number of units postrandomization (2 [1-4]; P > 0.05). There was no difference in the change in tissue oxygenation between groups. CPRBCs contained less α2-macrogobulin, haptoglobin, C-reactive protein, and serum amyloid P (P < 0.001). Organ failure, infection rate, and mortality did not differ between groups (P > 0.2). CONCLUSIONS: Transfusion of CPRBCs is as safe and effective as transfusion of young and old LPRBCs and provides a mechanism to deliver PRBCs in a wide variety of settings.

Effect of ascorbic acid concentrations on hemodynamics and inflammation following lyophilized plasma transfusion.

BACKGROUND: Compared with lyophilized plasma (LP) buffered with other acids, LP with ascorbic acid (AA) attenuates systemic inflammation and DNA damage in a combat relevant polytrauma swine model. We hypothesize that increasing concentrations of AA in transfused LP will be safe, will be hemodynamically well tolerated, and will attenuate systemic inflammation following polytraumatic injury and hemorrhage in swine. METHODS: This prospective, randomized, blinded study involved 52 female swine. Forty animals were subjected to our validated polytrauma model and resuscitated with LP. Baseline control sham (n = 6), operative control sham (n = 6), low-AA (n = 10), medium-AA (n = 10), high-AA (n = 10) groups, and a hydrochloric acid control (HCL, n = 10) were randomized. Hemodynamics, thrombelastography, and blood chemistries were assessed. Inflammatory cytokines (tumor necrosis factor α, interleukin 6 [IL-6], C-reactive protein, and IL-10) and DNA damage were measured at baseline, 2 hours, and 4 hours after liver injury. Significance was set at p < 0.05, with a Bonferroni correction for multiple comparisons. RESULTS: Hemodynamics, shock, and blood loss were similar between groups. All animals had robust procoagulant activity 2 hours following liver injury. Inflammation was similar between groups at baseline, and AA groups remained similar to HCL following liver injury. IL-6 and tumor necrosis factor α were increased at 2 hours and 4 hours compared with baseline within all groups (p < 0.008). DNA damage increased at 2 hours compared with baseline in all groups (p < 0.017) and further increased at 4 hours compared with baseline in HCL, low-, and high-AA groups (p < 0.005). C-reactive protein was similar between and within groups. IL-10 increased at 2 hours compared with baseline in low- and high-AA groups and remained elevated at 4 hours compared with baseline in the low-AA group (all, p < 0.017). CONCLUSION: Concentrations of AA were well tolerated and did not diminish the procoagulant activity of LP. Within our tested range of concentrations, AA can safely be used to buffer LP.

Aggressive aneurysmal bone cyst in association with polyostotic fibrous dysplasia: A case report.

INTRODUCTION: Aneurysmal bone cyst occurring in the setting of previously diagnosed fibrous dysplasia is rare. While both are benign processes, pain, compression of nearby structures and risk of fracture can require treatment. PRESENTATION OF CASE: In this report, we describe a 56 year old male who developed an aggressive aneurysmal bone cyst secondary to fibrous dysplasia in the proximal tibia over a period of 8 months. He required an above knee amputation for disease and symptom control due to the aggressive nature of disease and medical comorbidities. DISCUSSION: The diagnosis of a secondary lesion can prove difficult. It is important to exclude a malignant disease process, particularly when imaging demonstrates an aggressive appearance. In this case, repeat imaging, CT guided biopsies and an open biopsy were performed to exclude malignancy prior to definitive surgical management. CONCLUSION: In order to exclude secondary lesions, we suggest further investigation for new onset pain in the setting of a benign lesion.

Reconstitution fluid type does not affect pulmonary inflammation or DNA damage following infusion of lyophilized plasma.

BACKGROUND: Dysfunctional inflammation following traumatic hemorrhage can lead to multiple-organ failure and death. In our polytrauma swine model, lyophilized plasma (LP) reconstituted with sterile water and ascorbic acid suppressed systemic inflammation and attenuated DNA damage. However, it remains unknown whether the inflammatory response is affected by the type of fluid used to reconstitute LP. We hypothesized that common resuscitation fluids such as normal saline (LP-NS), lactated Ringer's solution (LP-LR), Hextend (LP-HX), or sterile water (LP-SW) would yield similar inflammation profiles and DNA damage following LP reconstitution and transfusion. METHODS: This was a randomized, prospective, blinded animal study. LP was reconstituted to 50% of original volume with NS, LR, HX, or SW buffered with 15-mM ascorbic acid. Forty swine were subjected to a validated model of polytrauma, hemorrhagic shock, and Grade V liver injury and resuscitated with LP. Serum interleukin 6 (IL-6), IL-10, plasma C-reactive protein, and 8-hydroxy-2-deoxyguanosine concentrations were assessed for systemic inflammation and DNA damage at baseline, 2 hours, and 4 hours following liver injury. Lung inflammation was evaluated by Real Time Polymerize Chain Reaction (RT-PCR). RESULTS: Reconstituted LP pH was similar between groups before resuscitation. IL-6 and IL-10 increased at 2 hours and 4 hours compared with baseline in all groups (p < 0.017). DNA damage increased at 2 hours and 4 hours compared with baseline and from 2 hours to 4 hours in the LP-NS, LP-LR, and LP-SW groups (all p < 0.017). Animals resuscitated with LP-HX not only demonstrated increased DNA damage at 4 hours versus baseline but also had the lowest C-reactive protein level at 2 hours and 4-hours (p < 0.017). Overall, differences between groups were similar for DNA damage and lung inflammation. CONCLUSION: Reconstitution fluid type does not affect inflammatory cytokine profiles or DNA damage following LP transfusion in this swine polytrauma model. Based on universal availability, these data suggest that sterile water is the most logical choice for LP reconstitution in humans. LEVEL OF EVIDENCE: Prognostic, level II.

Globus pallidus internus deep brain stimulation as rescue therapy for refractory dyskinesias following effective subthalamic nucleus stimulation.

BACKGROUND: Deep brain stimulation (DBS) at the subthalamic nucleus (STN) or globus pallidus internus (GPi) can effectively treat the motor symptoms of Parkinson's disease, but dual implantation is rare. We report the first cases of additional GPi stimulation as rescue therapy for disabling dyskinesias following successful STN stimulation. METHODS: Two patients, initially treated with bilateral STN DBS, underwent subsequent bilateral GPi DBS after the development of refractory dyskinesias within 1 and 6 years of STN surgery. Patients were evaluated with the Unified Parkinson's Disease Rating Scale (UPDRS) before and after surgeries for STN and GPi DBS. RESULTS: GPi DBS effectively suppressed dyskinesias in these patients and improved their quality of life, as demonstrated by their videos and UPDRS scores. CONCLUSIONS: Additional bilateral GPi DBS may be considered in the rare instance of patients who develop refractory dyskinesias early or late after bilateral STN DBS.

Comparison of the hemostatic efficacy of low-volume lyophilized plasma reconstituted using sterile water, lactated Ringer's, normal saline, and Hextend solutions.

BACKGROUND: Low-volume ascorbic acid-buffered reconstituted lyophilized plasma (LP) provides logistic advantages, reduces the risks for large-volume resuscitation, modulates inflammation, and is equally effective for hemostatic resuscitation as full-volume LP. We compared the physiologic effects of resuscitation using LP reconstituted with sterile water (LP-SW), lactated Ringer's solution (LP-LR), normal saline (LP-NS), and Hextend (LP-Hx). METHODS: Plasma was collected from swine, lyophilized, and then reconstituted into four test solutions: LP-SW, LP-LR, LP-NS, or LP-Hx. Forty swine were anesthetized and subjected to a validated model of polytrauma and hemorrhagic shock (including a Grade V liver injury), then randomized to receive one of the four test solutions. Physiologic parameters, blood loss, lactate, and hematocrit were followed up. Coagulation status was evaluated using thrombelastography. Inflammatory mediator expression was evaluated by multiplex serum assay. RESULTS: Forty animals were included in the study (10 animals per group). One animal died following LP-Hx resuscitation. There was less blood loss in the LP-SW and LP-LR groups compared with the LP-NS and LP-Hx groups (p < 0.05). The LP-SW group exhibited less early coagulopathic changes by thrombelastography, and the LP-Hx group had persistently elevated international normalized ratios at the end of the study period (p < 0.05). Serum interleukin 6 was lower after 4 hours in the LP-SW group compared with LP-NS (p < 0.05). CONCLUSION: Resuscitation using low-volume LP-SW and LP-LR buffered with ascorbic acid confers an anti-inflammatory benefit and results in less blood loss. Sterile water is a safe, cost-effective, and universally available fluid for creating a low-volume hemostatic LP resuscitation solution.

Circadian properties of cancer stem cells in glioma cell cultures and tumorspheres.

Increased cancer risk is linked to disruption of circadian rhythms. Cancer stem cells (CSCs) are a known cause of cancer aggressiveness, but their circadian properties have not been described. We discovered circadian rhythms in gene expression within C6 glioma tumorspheres enriched in CSCs and found that the circadian clock is particularly robust in medium lacking any growth factors. A method is introduced for identifying individual CSCs in culture for single-cell analysis. CSCs in monolayer cell culture failed to show a circadian rhythm in nuclear localization of mPER2 protein, suggesting that cell interactions or the tumor-like microenvironment within tumorspheres enable circadian timing.