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Background: Many syndesmosis screw fixations do not achieve success at the first attempt. Currently, there are no data available to evaluate revision of syndesmosis screw failure. Methods: A total of 160 consecutive patients who underwent syndesmosis screw fixation from 2014 to 2016 were reviewed. The current study focuses on 13 of 160 patients who underwent revision surgery and analyzes reasons, methods, and outcomes of syndesmotic screw revisions. Results: Thirteen out of 160 patients had revision surgeries. Incidence of recurrent diastasis was 92.3%. Seven out of 19 screws had broken. Two patients had screw loosening, 9 patients underwent early weightbearing, 1 patient developed osteomyelitis, 1 patient developed osteoarthritis, and 1 patient had fibular nonunion. Eleven patients underwent removal, 3 patients underwent clamp reduction, and 4 patients underwent fibular osteotomy. Six patients experienced good reduction with 0/10 pain, 3 patients experienced good reduction with some pain, 1 patient experienced poor reduction; 1 patient developed osteomyelitis and subsequent 7/10 pain; 1 patient underwent fusion with 5/10 pain, and 1 patient experienced medial malleolar mal-union with 3/10 pain. Conclusion: It was found that the main reason for syndesmosis revision was reoccurring diastasis. Most patients ultimately experienced good reduction and were able to ambulate, despite some residual pain. Levels of Evidence: Level IV: Case series

BACKGROUND AND OBJECTIVES Retinopathy of prematurity (ROP) is a leading cause of childhood blindness. Screening and treatment reduces this risk, but requires multiple examinations of infants, most of whom will not develop severe disease. Previous work has suggested that artificial intelligence may be able to detect incident severe disease (treatment-requiring retinopathy of prematurity [TR-ROP]) before clinical diagnosis. We aimed to build a risk model that combined artificial intelligence with clinical demographics to reduce the number of examinations without missing cases of TR-ROP. METHODS Infants undergoing routine ROP screening examinations (1579 total eyes, 190 with TR-ROP) were recruited from 8 North American study centers. A vascular severity score (VSS) was derived from retinal fundus images obtained at 32 to 33 weeks’ postmenstrual age. Seven ElasticNet logistic regression models were trained on all combinations of birth weight, gestational age, and VSS. The area under the precision-recall curve was used to identify the highest-performing model. RESULTS The gestational age + VSS model had the highest performance (mean ± SD area under the precision-recall curve: 0.35 ± 0.11). On 2 different test data sets (n = 444 and n = 132), sensitivity was 100% (positive predictive value: 28.1% and 22.6%) and specificity was 48.9% and 80.8% (negative predictive value: 100.0%). CONCLUSIONS Using a single examination, this model identified all infants who developed TR-ROP, on average, >1 month before diagnosis with moderate to high specificity. This approach could lead to earlier identification of incident severe ROP, reducing late diagnosis and treatment while simultaneously reducing the number of ROP examinations and unnecessary physiologic stress for low-risk infants.

Objective: To review efficacy, safety, and place in therapy of solriamfetol for management of excessive daytime sleepiness (EDS) in patients with narcolepsy and obstructive sleep apnea (OSA). Methods: PubMed (1966 to January 2021) was searched using the terms solriamfetol, JZP-110, ADX-N05 and Sunosi. Human studies published in peer-reviewed medical journals in English language were reviewed. Results: The efficacy and safety of solriamfetol has been reported in 2 phase II trials and 4 phase III trials (TONES 2, TONES 3, TONES 4, and TONES 5). Statistically significant improvements in the maintenance of wakefulness test were reported with solriamfetol 150 mg and 300 mg vs placebo in participants with narcolepsy (7.65- to 10.14-minute difference from placebo). In subjects with OSA, statistically significant improvements in maintenance of wakefulness test difference from placebo were also observed in those taking solriamfetol 75 mg, 150 mg, or 300 mg vs placebo (4.5- to 12.8-minute difference from placebo). Statistically significant reductions in Epworth Sleepiness Scale scores were also reported in phase III trials in subjects with narcolepsy or OSA taking solriamfetol vs placebo (ranging from − 4.7 to − 1.9 difference from placebo). Common adverse events in reported in phase III trials were headache, nausea, decreased appetite, anxiety, dry mouth, and diarrhea. Solriamfetol appears to have a reduced risk for drug interactions and fewer adverse effects compared to other agents available for management of EDS in patients with narcolepsy and OSA. Conclusions: Solriamfetol is an effective option for management of EDS in patients with narcolepsy and OSA.

Carnitine-acylcarnitine translocase (CACT) deficiency is a rare disorder of long chain fatty acid oxidation with a very high mortality rate due to cardiomyopathy or multiorgan failure. We present the course of a very premature infant with early onset CACT deficiency complicated by multiple episodes of necrotizing enterocolitis, sepsis, and liver insufficiency, followed by eventual demise. The complications of prematurity, potentiated by the overlay of CACT deficiency, contributed to the difficulty of reaching the ultimate diagnosis of CACT deficiency.

Background: After injection into a brachial vein, high contrast media concentration in axillary and subclavian veins can cause artifacts that impair diagnostic utility. This study assessed artifact reduction by artifact-reduction-algorithms (ARA) and virtual-monoenergetic-images (VMI), as well as their combination (VMIARA) compared to conventional CT-images (CI). Methods: Forty-six spectral-detector-CT (SDCT) examinations of patients that received ARA-reconstructions due to perivenous-artifacts were included in this retrospective study. CI, ARA, VMI, and VMIARA (range: 70-200 keV) were reconstructed. Objective analysis was performed with ROI-based assessment of mean and standard deviation of attenuation (HU) in hypo- and hyperdense artifacts and impaired muscle and arteries as well as artifact-free reference-tissue. Extent of artifact reduction, assessment of surrounding soft tissue and vessels, and appearance of new artifacts were rated visually by two radiologists. Results: Hypo- and hyperdense artifacts showed significant improvement as evidenced by decreasing attenuation differences between artifact impaired and artifact-free reference tissue in ARA, VMI ≥80 keV, and VMIARA between 70-200 keV (e.g., CI/ARA/VMI100keV/VMIARA100keV: hypodense artifacts, (-)264.8±150.9/(-)87.1±78.9/(-)48.6±64.6/9.9±63.9 HU; P

We established an international consortium to review and discuss relevant clinical evidence in order to develop expert consensus statements related to cancer management during the severe acute respiratory syndrome coronavirus 2-related disease (COVID-19) pandemic. The steering committee prepared 10 working packages addressing significant clinical questions from diagnosis to surgery. During a virtual consensus meeting of 62 global experts and one patient advocate, led by the European Society for Medical Oncology, statements were discussed, amended and voted upon. When consensus could not be reached, the panel revised statements until a consensus was reached. Overall, the expert panel agreed on 28 consensus statements that can be used to overcome many of the clinical and technical areas of uncertainty ranging from diagnosis to therapeutic planning and treatment during the COVID-19 pandemic.

For healthy individuals, it is increasingly accepted that lung function follows along an individual percentile established early in life and that the level of maximal function reached as a young adult can affect the subsequent development of lung disease that occurs with the normal aging process. This emphasizes the need to maximize early lung function. The trajectories of lung function are at least partially established by perinatal factors, including prematurity and in utero exposures (tobacco exposure, nutrition, inflammation, etc), although they can also be affected by a variety of additional factors and exposures throughout the life span. Whether lung function trajectories can be impacted or reset if established under suboptimal conditions is an unanswered question, offering new avenues for research. In this review, we will summarize important articles outlining lung function trajectories and linking pediatric lung function tests to adult lung function tests decades later. We will focus on perinatal factors and outline progress and opportunities for further investigation into the potential ability to reset trajectories to impact long-term lung health.

Objective: To review the efficacy, safety, and place in therapy of ixekizumab for the treatment of moderate to severe plaque psoriasis. Data Sources: PubMed (1966 to July 2018) and clinicaltrials.gov were searched using the terms ixekizumab, LY2439821, interleukin-17, and psoriasis. Study Selection and Data Extraction: Human studies published in peer-reviewed medical journals in English were used. Data Synthesis: The efficacy and safety of ixekizumab has been primarily reported by 4 phase III trials (UNCOVER-1, UNCOVER-2, UNCOVER-3, and UNCOVER-J) and multiple post hoc analyses. The average proportions of patients achieving a 75%, 90%, and 100% reduction in their Psoriasis Area and Severity Index (PASI) were 89%, 70%, and 38%, respectively, after 12 weeks of therapy. PASI75 was maintained for up to 3 years in 80.5% of participants. Ixekizumab was statistically significantly more effective than ustekinumab, with 76.5%, compared with 59%, of patients achieving PASI90 in 52 weeks. The most common adverse events include nasopharyngitis (14.1%), upper respiratory tract infections (7.9%), and injection-site reactions (6.8%), which are similar to that for other biological agents. The risk of inflammatory bowel disease may be increased with ixekizumab. Relevance to Patient Care and Clinical Practice: This review summarizes and evaluates clinical data regarding the efficacy and safety of ixekizumab and discusses relevant differences compared with other biological agents used for the management of chronic plaque psoriasis. Conclusions: Ixekizumab is a highly efficacious and well-tolerated treatment option for patients with moderate to severe plaque psoriasis.

Objective To evaluate if premature infants delivered ≤7 days after rescue antenatal steroid treatment (ideal treatment) have increased passive respiratory compliance compared to those delivered ˃7 days after treatment (remote treatment). Methods Secondary analysis of a randomized trial of rescue antenatal steroids on respiratory compliance. Infants in the treatment group were stratified by the interval between rescue antenatal steroids and delivery. We then compared the respiratory compliance in the ideal versus remote groups. Results 44 women (56 infants) received rescue antenatal steroids. 49 infants had evaluable respiratory compliance measurements, with 27 (GA 30.0 weeks, BW 1362g) “ideally” treated, and 22 (GA 33.8 weeks, BW 2248g) “remotely” treated. Respiratory compliance was significantly higher for the ideal compared to the remote group (1.32 vs 1.06 mL/cm H20/kg; p = 0.037). Conclusion Infants treated with rescue antenatal steroids have a significantly higher respiratory compliance if delivery occurs within 7 days after treatment.

Objective/Purpose Retinopathy of prematurity (ROP) is a leading cause of childhood blindness related to oxygen exposure to the developing retina in premature infants. Since oxygen monitoring protocols have reduced the incidence of treatment-requiring ROP (TR-ROP), it remains unclear whether oxygen exposure remains a relevant risk factor for incident TR-ROP and aggressive ROP (A-ROP), a severe, rapidly progressing form of ROP. The purpose of this proof-of-concept study was to use electronic health record (EHR) data to evaluate early neonatal oxygen exposure as a predictive variable for developing TR-ROP and A-ROP. Design Retrospective cohort study. Subjects, Participants, and/or Controls 244 infants screened for ROP at a single academic center. Methods Intervention, or Testing: For each infant, oxygen saturations and fraction of inspired oxygen (FiO₂) were manually extracted from the EHR until 31 weeks PMA. Cumulative minimum, maximum, mean oxygen saturation and FiO₂ were calculated on a weekly basis. Random forest models were trained with 5-fold cross-validation using GA and cumulative minimum FiO₂ at 30 weeks PMA to identify infants who developed TR-ROP. Secondary ROC analysis on infants with/without A-ROP was performed without cross-validation due to small numbers. Main Outcomes/Measures For each model, cross-validation performance for incident TR-ROP was assessed using area under the receiver operating curve (AUROC) and precision-recall curve (AURPC) scores. For A-ROP, we calculated AUROC, and evaluated sensitivity and specificity at a high-sensitivity operating point. Results Of the 244 infants included, 33 developed TR-ROP and 5 were diagnosed with A-ROP. For incident TR-ROP, random forest models trained on GA plus cumulative minimum FiO₂ (AUROC=0.93±0.06, AUPRC=0.70±0.08) were not significantly better those trained on GA alone (AUROC=0.92±0.06, p=0.59; AUPRC=0.74±0.12, p=0.32). However, models using oxygen alone had an AUROC of 0.80±0.09. Secondary ROC analysis for A-ROP found an AUROC=0.92 [95% CI 0.87-0.96]. Conclusions Oxygen exposure can be extracted from the EHR and quantified as a risk factor for incident TR-ROP and A-ROP. Extracting quantifiable clinical features from the EHR may be useful in the future for building integrative risk models for multiple diseases, and evaluating the complex relationships between oxygen exposure, ROP, and other sequelae of prematurity.

The goal of the present study was to perform a systematic review of the published data on talar neck fractures for a better understanding of the postoperative clinical outcomes using open reduction and internal fixation stratified by Hawkins type. A PubMed search was performed using the keywords "talar," "neck," and "fracture." This search identified 209 potential studies, which were reviewed to yield 16 studies that met the criteria. The surgical outcomes of talar neck fractures stratified by the Hawkins classification analyzed in the present study were as follows: American Orthopaedic Foot and Ankle Society scale score was 77.00 for type I, 86.10 for type II, 68.30 for type III, 68.30 for type IV, and 76.50 for all talar neck fractures. Avascular necrosis presented in 0.00% of type I fractures, 15.91% of type II fractures, 38.89% of type III fractures, 55.00% of type IV fractures, and 26.47% of all fractures. Osteoarthritis presented in 25.00% of type I fractures, 41.33% of type II fractures, 54.23% of type III fractures, 72.73% of type IV fractures, and 51.69% of all fractures. Subtalar arthritis presented in 0.00% of type I fractures, 54.29% of type II fractures, 46.43% of type III fractures, 45.45% of type IV fractures, and 44.97% of all fractures. The malunion prevalence was 13.29% and the nonunion prevalence was 3.97% for all fractures. Type II fractures were the most common (50.88%) fracture type reported in the reports reviewed in the present study.

Medical student wellness is of great concern in the health care field. A growing number of studies point to increases in suicide, depression, anxiety, mood disorders, and burnout related to physician lifestyles. Mental health issues commencing in medical school have been suggested to have a significant impact on future physician lifestyle and burnout. Tracking the mental health of medical students at the University of Toledo College of Medicine and Life Sciences (UTCOMLS) with standardized indices will help elucidate triggers of poor mental health. Anonymous surveys were developed and distributed to preclinical medical students at five strategic time points throughout the 2018 2019 academic year. Surveys collected basic demographic information as well as inventories measuring perceived stress, burnout, resilience, and mindfulness. 172 M1s (83 males and 89 females) were included in the study and average response rate for the first 4 (out of 5) surveys averaged 74.8%. M1 males and females had on average increased personal burnout over time with females consistently scoring higher. Both males and females had an increase in stress from August to each subsequent month (p

Introduction Adherence to positive airway pressure (PAP) therapy continues to be a challenge. The main objective of this study was to determine whether mobile text-message reminders increased PAP adherence in veterans with obstructive sleep apnea. Methods This is a retrospective study of 25 patients with poor adherence to PAP therapy who used the Veterans Affairs ANNIE app to receive nightly mobile text message reminders. PAP adherence was measured at baseline, 1,and 3 months. A one-way repeated measures ANOVA was used to compare the effect of time on PAP adherence, specifically the percentage of overall days used and percentage use >4 hours. A two-way repeated measures ANOVA without replication was used to determine the effects of AHI severity and time on PAP adherence. Results Our sample demographics included a mean age of 59 ±12 years, mean BMI of 33.5% ±5.4, and mean AHI of 26.3 ±25.4. The mean PAP overall percentage use and mean use >4 hours respectively were 32% ± 27 and 18% ± 19 at baseline, 66% ± 27 and 45% ± 30 at 1 month, and 54% ±32 and 37% ± 30 at 3 months. After three months of receiving nightly text-message reminders, there was a statistically significant effect of time on percentage overall PAP use, F (2, 48)=21.54, p=2.10E-07, as well as in the percentage PAP use >4 hours, F (2, 48)=22.05, p=1.61E-07. A two-way repeated measures ANOVA without replication yielded a main effect of the interaction of time with PAP adherence, F (2, 48)=22, p= Conclusion Nightly text message reminders significantly improved PAP adherence from baseline to 3 months. Though PAP adherence was not optimal, it doubled initially in our sample. Further studies are warranted to determine how text-messages can be used long term to improve adherence. Support Nil

Background A single nucleotide polymorphism within the phosphatase PTPN22 increases the risk of developing multiple autoimmune and connective tissue diseases.1 Ptpn22 is a negative regulator of Syk and Src family kinases downstream of immuno-receptor signalling cascades.2 Fungal β-glucan receptor dectin-1, signals via Syk kinase, and induces dendritic cells to secrete pro-inflammatory cytokines IL-1β, IL-6, IL-12/23p40 and TNFα, in turn allowing the induction of IL-17 secreting T-cell responses, which are critical to the clearance of fungal infections.3 IL-17 has been implicated as a key cytokine in inflammatory responses associated with RA, JIA, and psoriasis.4 Objectives To investigate if Ptpn22 regulates dectin-1 signalling and controls the capability of dectin-1 matured BMDC to promote adaptive immune responses. Methods GM-CSF bone marrow derived dendritic cells (BMDC) were generated from C57BL/6 WT, Ptpn22-/- or Ptpn22R619W (human PTPN22R620W orthologue) mice, and pulsed with OVA323–339 in the presence or absence of the dectin-1 agonist curdlan. Activated BMDC were co-cultured in vitro with OT-II T-cells or adoptively transferred into OT-II mice and the resulting T-cell response assessed. Cytokine secretion from curdlan activated Ptpn22 variant mouse BMDC was determined by immunoassay and the kinetics of Syk and Erk phosphorylation were determined by immunoblot. Results We observed that Dectin-1 activated Ptpn22-/- BMDC had an enhanced capability to induce T-cell IL-17 secretion both in vitro and in vivo compared to WT BMDC. Following dectin-1 priming Ptpn22-/- BMDC secreted increased IL-1β compared to WT BMDC, and the increase in IL-1β was found to be sufficient to cause the enhanced IL-17 response induced by Ptpn22-/- BMDC. Dectin-1 induced IL-1β secretion was found to be Syk and Erk dependent and assessment of Syk and Erk kinetics of phosphorylation revealed that dectin-1 activated Ptpn22-/- BMDC displayed enhanced Syk and Erk phosphorylation compared to WT BMDC. Furthermore, Ptpn22R619W BMDC (orthologue of human Ptpn22R620W) exhibited a similar enhancement in IL-1β secretion and induced enhanced T-cell dependent IL-17 responses in vivo, indicating that the PTPN22 polymorphism behaves as a loss-of-function allele in the context of dectin-1 signals. Conclusions Data highlight Ptpn22 as a novel regulator of dectin-1 signals and provide a link between genetically conferred perturbation to innate receptor signalling pathways and autoimmunity. References Burn, G. L., Svensson, L., Sanchez-Blanco, C., Saini, M. & Cope, A. P. Why is PTPN22 a good candidate susceptibility gene for autoimmune disease? FEBS Lett. 585, 3689–98 (2011). Cloutier, J. F. & Veillette, A. Cooperative inhibition of T-cell antigen receptor signaling by a complex between a kinase and a phosphatase. J. Exp. Med. 189, 111–21 (1999). Dambuza, I. M. & Brown, G. D. C-type lectins in immunity: recent developments. Curr. Opin. Immunol. 32, 21–27 (2015). Tabarkiewicz, J., Pogoda, K., Karczmarczyk, A., Pozarowski, P. & Giannopoulos, K. The Role of IL-17 and Th17 Lymphocytes in Autoimmune Diseases. Arch. Immunol. Ther. Exp. (Warsz). 63, 435–49 (2015). Disclosure of Interest None declared

Objective: To describe the current data evaluating the efficacy and safety of memantine for the prevention of primary headache disorders. Data Sources: A literature search using MEDLINE (1966-July 2014) and EMBASE (1973-July 2014) was conducted using the search terms memantine, headache, migraine, glutamate, and NMDA. References of identified articles were reviewed for additional, relevant citations. Study Selection and Data Extraction: All English-language articles dealing with the use of memantine for prevention of primary headache disorders were included. Data Synthesis: Data from several retrospective reports and 2 prospective clinical trials suggest that memantine may be a useful treatment option for the prevention of primary headache disorders. The majority of available literature focuses specifically on chronic migraine prevention in refractory patients who had failed multiple previous prophylactic therapies. In these patients, 10 to 20 mg of memantine daily reduced the frequency and intensity of migraine headaches and was generally well tolerated, with few adverse events. Data regarding the efficacy of memantine for other primary headache disorders such as chronic tension type and cluster headaches are limited. Conclusion: Although further studies evaluating the efficacy of memantine for prevention of primary headache disorders are warranted, memantine may be a reasonable option, used either as monotherapy or adjunctive therapy, in the refractory chronic migraine prophylaxis setting.

CONTEXT: The effectiveness of tonsillectomy or adenotonsillectomy (hereafter, “tonsillectomy”) for obstructive sleep-disordered breathing (OSDB) compared with watchful waiting with supportive care is poorly understood. OBJECTIVE: To compare sleep, cognitive or behavioral, and health outcomes of tonsillectomy versus watchful waiting with supportive care in children with OSDB. DATA SOURCES: Medline, Embase, and the Cochrane Library. STUDY SELECTION: Two investigators independently screened studies against predetermined criteria. DATA EXTRACTION: Two investigators independently extracted key data. Investigators independently assessed study risk of bias and the strength of the evidence of the body of literature. Investigators synthesized data qualitatively and meta-analyzed apnea–hypopnea index (AHI) scores. RESULTS: We included 11 studies. Relative to watchful waiting, most studies reported better sleep-related outcomes in children who had a tonsillectomy. In 5 studies including children with polysomnography-confirmed OSDB, AHI scores improved more in children receiving tonsillectomy versus surgery. A meta-analysis of 3 studies showed a 4.8-point improvement in the AHI in children who underwent tonsillectomy compared with no surgery. Sleep-related quality of life and negative behaviors (eg, anxiety and emotional lability) also improved more among children who had a tonsillectomy. Changes in executive function were not significantly different. The length of follow-up in studies was generally LIMITATIONS: Few studies fully categorized populations in terms of severity of OSDB; outcome measures were heterogeneous; and the durability of outcomes beyond 12 months is not known. CONCLUSIONS: Tonsillectomy can produce short-term improvement in sleep outcomes compared with no surgery in children with OSDB. Understanding of longer-term outcomes or effects in subpopulations is lacking.

Respiratory distress syndrome (RDS) is the leading cause of neonatal morbidity and mortality in premature infants. It is caused by surfactant deficiency and lung immaturity. Lucinactant is a synthetic surfactant containing sinapultide, a bioengineered peptide mimic of surfactant-associated protein B. A meta-analysis of clinical trials demonstrates that lucinactant is as effective as animal-derived surfactants in preventing RDS in premature neonates, and in vitro studies suggest it is more resistant to oxidative and protein-induced inactivation. Its synthetic origin confers lower infection and inflammation risks as well other potential benefits, which may make lucinactant an advantageous alternative to its animal-derived counterparts, which are presently the standard treatment for RDS.

Introduction The use of fractional flow reserve (FFR) as the gold standard for functional assessment of intermediate coronary stenosis has been well documented. Intracoronary imaging techniques such as intravascular ultrasound (IVUS) have been used for additional coronary lesion resolution and some of its anatomic parameters have been studied as having possible correlation with FFR, particularly IVUS minimal lumen area (MLA). We performed a comprehensive review of the available literature in the area. Evidence acquisition A Pubmed search was performed for all the literature involving comparison of diagnostic accuracy of IVUS-MLA with FFR. Evidence synthesis An extensive description of all the available data regarding IVUS-MLA diagnostic value regarding the FFR of stenotic lesions, for both non-left main (non-LM) and left main (LM) lesions. Conclusions For non-LM lesions IVUS-MLA cutoff values to identify specific FFR thresholds have marked heterogeneity and perform particularly poorly in terms of specificity and positive predictive value. For LM lesions IVUS-MLA performs better and shows a better correlation with FFR, though more data is needed to confirmed that trend.

Allogeneic myeloablative haematopoietic stem cell transplantation (HSCT) is challenged by severe adverse events, as cytotoxic effects of the conditioning may result in systemic inflammation, leaky epithelial barriers and organ toxicities, contributing to treatment-related morbidity and mortality. We hypothesised that insulin-like growth factor-1 (IGF-1), a mediator of growth and proliferation of various tissues, may attenuate chemotherapy-induced tissue damage after HSCT. We prospectively measured plasma levels of IGF-1 and its binding protein 3 (IGFBP-3) in 41 patients undergoing myeloablative HSCT. IGF-1 and IGFBP-3 levels were inversely correlated with C-reactive protein and interleukin-6 levels post HSCT. In multivariate analyses, low levels of IGF-1 and IGFBP-3 before conditioning were associated with increased risk of developing sinusoidal obstruction syndrome (SOS; OR=5.00 per 1 SDS decrease in IGF-1 (95% CI: 1.45–16.67), P=0.011 and OR=5.00 (1.37–20.00), P=0.015, respectively). Furthermore, low pre-transplant levels of IGF-1 and IGFBP-3 were associated with increased fluid retention during the first 21 days post transplant (OR=7.69 (95% CI: 1.59–33.33), P=0.012, and OR=2.94 (1.03–8.33), P=0.045). These data suggest that high levels of IGF-1 and IGFBP-3 may have a protective effect against fluid retention and SOS, possibly by attenuating systemic inflammation, and may prove useful as predictive biomarkers of SOS.

Die neuen, oral verabreichten Zytostatika vom Typ der Tyrosinkinasehemmstoffe (TKI) z. B. gegen den Wachstumsfaktor-Rezeptor EGFR/HER2 (Epidermal growth factor receptor) sind mit typischen Nebenwirkungen wie Hautveranderungen und Diarrhoen assoziiert. Auch wenn diese klinisch meist mild und nicht vital gefahrdend sind, kann die psychische Belastung fur den Patienten erheblich sein und bis zum Therapieabbruch fuhren. Durch die einfache orale Administration kommen EGFR-TKI aus den Fachkliniken zunehmend in den Bereich der niedergelassenen Arzte. Daher soll dieser Review dem niedergelassenen Arzt konkrete Handlungsanweisungen zur Bewertung und Therapie der haufigsten Nebenwirkungen an die Hand geben. Mittlerweile sind mehrere TKI zugelassen, weitere, wie beispielsweise Afatinib, befinden sich in spaten Stadien der klinischen Prufung. Afatinib ist eine Substanz der neuesten Generation (irreversible TKI) mit breiterem TKI-Spektrum (Erb familyblocker) und den klassentypischen Nebenwirkungen. Gastrointestinale Nebenwirkungen wie Durchfall sind insbesondere zu Behandlungsbeginn haufig, konnen aber analog zu Chemotherapeutika nach dem hier vorgestellten Schema auf Basis von Loperamid und ggf. Octreotid behandelt werden. Stomatitis/Mukositis konnen durch gezielte Pflege und Kuhlung gelindert werden. Fur akneiforme Dermatitiden ist in Abhangigkeit vom Schweregrad eine gezielte topische oder systemische Antibiose in Verbindung mit weiteren lokalen Masnahmen sinnvoll. Fatigue ist bei Afatinib eine eher seltener auftretende, dennoch ernst zu nehmende Nebenwirkung.

An evidence-based systematic review including written and statistical analysis of scientific literature, expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.

Embrittlement threatens the useful lifetime of books, maps, manuscripts, and works of art on paper during storage, circulation, and display in libraries, museums, and archives. Past studies have traced much of the embrittlement to the Bronsted-acidic conditions under which printing papers have been made, especially during the period between the mid 1800s to about 1990. This article reviews measures that conservators and collection managers have taken to reduce the acidity of books and other paper-based materials, thereby decreasing the rates of acid-catalyzed hydrolysis and other changes leading to embrittlement. Technical challenges include the selection of an alkaline additive, selecting and implementing a way to distribute this alkaline substance uniformly in the sheet and bound volumes, avoiding excessively high pH conditions, minimizing the rate of loss of physical properties such as resistance to folding, and avoiding any conditions that cause evident damage to the documents one is trying to preserve. Developers have achieved considerable progress, and modern librarians and researchers have many procedures from which to choose as a starting point for further developments.

To account for intra-fractional patient movement during stereotactic radiosurgery, Cyberknife utilises two orthogonal ceiling mounted kV sources that can be used to track patient movement with a variable imaging interval of between 15 and 150 s according to the user's discretion. Imaging intervals can be optimised to keep imaging dose to a minimum while retaining delivery accuracy. Log files recorded during the treatment delivery can be used to establish both optimum imaging interval and also a suitable treatment margin to account for the patient movement that cannot be accounted for by imaging. Log files for 56 intracranial patients (100 fractions, 5000 image pairs) were retrospectively assessed for patient movement. Movement between consecutive images was investigated, along with the movement of the patient over the duration of the treatment. It was found that from image to image, patient movement did not vary with respect to interval times. The standard deviation (SD) for the movement between images was found to be 0.32, 0.36 and 0.33 mm for superior/inferior (SI), left/right (LR) and anterior/posterior (AP) movement respectively. The rate of drift between the images was used to calculate that an interval of 28 s was required to restrict the translational movement of the patient to 0.1 mm for 95% of the population. As no relationship could be found between the interval times and movement, it cannot be assumed that the patient movement between images is linear. This movement cannot be accounted for by additional imaging but could be accounted for using additional planning margins. This work shows that log files that have been verified can be used to create treatment margins and imaging intervals. To ensure target coverage, a 0.8 mm margin (0.7 for stochastic and 0.1 for systematic) is recommended, and an imaging interval of 30 s.

Law, R.-J., Breslin, A., Oliver, E., Mawn, L., Markland, D., Maddison, P., Thom, J. (2010). Exercise and rheumatoid arthritis: what's in it for us? Poster 288 in: Abstracts of the Rheumatology BSR and BHPR Conference, 21-23 April 2010, Rheumatology, 49(suppl 1), i139-i143.

Purpose The purpose of this study was to determine the current perceptions of drug information practice and training. Methods Electronic surveys were sent to 417 pharmacists who likely would have drug information responsibilities. The survey collected information regarding job responsibilities, perceived importance of each responsibility to drug information practice, type of postgraduate training received to prepare for responsibilities, and perceived adequacy of training. Results There were 206 survey respondents. The most frequently cited primary job responsibilities were providing instruction to students and staff, operating drug information centers, and responding to drug information queries. Most respondents felt that educational instruction, pharmacy and therapeutics (P&T) committee support, and responding to drug information questions were very important to drug information practice. On-the-job experience was cited as the most frequent source of training. Of the respondents, 46% reported completion of a pharmacy practice residency and 40% reported completion of a drug information specialty residency, with 14% completing both. Fifteen percent of respondents had no postgraduate training. Most respondents felt prepared for current job responsibilities after postgraduate training, with the exceptions of information systems support, pharmacoeconomic evaluations, and clinical outcomes research. Conclusion Despite earlier recommendations, drug information job responsibilities within the study sample have changed little over the past decade. Respondents felt that most of their job responsibilities are important to drug information practice and that postgraduate training adequately prepared them for most of these responsibilities. However, only 40% of respondents received specialized training in drug information practice.

Eine leitliniengerechte antiemetische Prophylaxe und Therapie vor der Chemotherapie stellt eine unbedingte Grundvoraussetzung fur eine erfolgreiche Chemotherapie dar. Durch den Einsatz der modernen Antiemetika ist es inzwischen moglich, Ubelkeit und Erbrechen weitestgehend zu verhindern. Dabei muss zwischen akutem und verzogertem Erbrechen differenziert werden. Zu den wichtigsten Antiemetika zahlen die 5-HT3-Rezeptor-Antagonisten (5-HT3-RA), die Neurokinin-1-Rezeptor-Antagonisten (NK1-RA) und auch die Steroide. Die alltagliche klinische Praxis erfordert die Kenntnis der emetogenen Potenz der einzelnen Zytostatika, um eine leitliniengerechte antiemetische Prophylaxe anzuwenden.

Testicular non-seminoma: ESMO Clinical Recommendations for diagnosis, treatment and follow-up H.-J. Schmoll, K. Jordan, R. Huddart, M. P. Laguna, A. Horwich, K. Fizazi & V. Kataja On behalf of the ESMO Guidelines Working Group* Department of Oncology/Haematology/Haemostaseology, University Hospital Halle, Halle, Germany; Department of Academic Radiotherapy, Institute of Cancer Research, Royal Marsden Hospital, Sutton Hospital, UK; Department of Urology, AMC University Hospital, Amsterdam, The Netherlands; Department of Medicine, Institute Gustave Roussy, Villejuif, France; Department of Oncology, Kuopio University Hospital, Kuopio and Vaasa Central Hospital, Vaasa, Finland

A novel multielectrode dielectric-barrier discharge plasma system operating at atmospheric pressure in air, which has improved microbial inactivation properties is described. The interaction of high-voltage components necessary to create the discharge is outlined, and the unique configuration of electrodes driven by power insulated gate bipolar transistors is put forward. Active species gain is in evidence in this system due to the effective feedforward mechanism employed and are validated by carrying out microbial inactivation studies on E. coli. Both active species gain and microbial inactivation hypotheses are verified by numerical modeling.

PurposeThe patient journey from detection of an eye problem by optometrists to assessment and treatment by ophthalmologists can be streamlined by direct referral from optometrist to hospital eye service (HES). This requires locally agreed guidelines and training and feedback for optometrists to ensure high diagnostic competence. The purpose of this paper is to evaluate the quality of the West Suffolk Direct Referral Scheme, one of the first direct referral schemes in the UK to include all ophthalmic sub‐specialties.Design/methodology/approachTwo‐cycle audit of existing practice, including all new patients referred by optometrists and seen at West Suffolk Hospital during a three‐month period in 2003 and a seven‐week period in 2006. Three interventions: direct referral clinics for urgent patients; introduced in 2003; six‐monthly training sessions for optometrists; and regular, prompt feedback via letter about individual consultation outcome. Prospective data collection via proforma in both cycles; additional retrospective data collection in the second cycle. Diagnostic accuracy, perception of urgency and request of subspecialty clinic were evaluated.FindingsThe direct referral scheme streamlines the patient journey, and patients with acute problems have fast access to HES. In total, 99 per cent of referrals are appropriate. Diagnostic competence is high (87 per cent), and has improved with tighter communication between HES and optometrists. Agreement is less for referral urgency (75 per cent) and choice of subspecialty clinic (74 per cent).Originality/valueThe West Suffolk Direct Referral Scheme provides an efficient service of high quality. Good communications and continued feedback between community‐ and hospital‐based eye care services improve standards and facilitate efficient use of resources.

Atherosclerosis is a chronic inflammatory disease involving plaque buildup in the arteries and can lead to heart attack and stroke. A key step in the pathogenesis of atherosclerosis is oxLDL uptake...

Die Verhinderung von chemotherapieinduzierter Ubelkeit und Erbrechen zahlt zu den wichtigsten supportiven Begleittherapien, da diese Nebenwirkungen der Chemotherapie fur die Patienten nach wie vor mit die unangenehmsten sind. Im vorliegenden Artikel wird das leitliniengerechte Vorgehen in der antiemetischen Prophylaxe und Therapie vorgestellt. Zudem werden die verschiedenen Antiemetika praxisnah beschrieben.

OBJECTIVE: To review the pharmacology, efficacy, and safety of efalizumab for the treatment of moderate to severe plaque psoriasis. DATA SOURCES: A MEDLINE search (1966–May 2005%) using the key words hu1124, anti-CD11a, efalizumab, Raptiva, Xanelim, and psoriasis was conducted. References of identified articles were reviewed for additional citations. STUDY SELECTION AND DATA EXTRACTION: Clinical trials evaluating the pharmacology, efficacy, and safety of efalizumab for treatment of moderate to severe plaque psoriasis in adults were included in our review. DATA SYNTHESIS: Efalizumab's ability to inhibit the binding of CD11a, a subunit of leukocyte function–associated antigen type 1, to intracellular adhesion molecule 1 results in decreased T-cell activation and migration, 2 key steps in the immunopathogenesis of psoriasis. Results of clinical trials have demonstrated that efalizumab administered subcutaneously is a safe and effective treatment for moderate to severe plaque psoriasis. Efalizumab was well tolerated in trials, with the majority of adverse events arising with the first dose and decreasing with subsequent doses. The high cost of this agent and lack of head-to-head trials with other drugs will likely restrict its use to patients who have failed prior systemic therapy or phototherapy. CONCLUSIONS: Efalizumab is a safe and effective therapy for treatment of moderate to severe plaque psoriasis in patients who have failed prior systemic therapy or phototherapy.

Superparamagnetic iron oxide (SPIO) nanoparticles are being used for intracellular magnetic labeling of stem cells and other cells in order to monitor cell trafficking by magnetic resonance imaging (MRI) as part of cellular-based repair, replacement and treatment strategies. This review focuses on the various methods for magnetic labeling of stem cells and other mammalian cells and on how to translate experimental results from bench to bedside.

To estimate the prevalence of posterior embryotoxon (PE) in the general ophthalmic clinic and to identify any features of PE that suggest that it is pathological rather than physiological. Over 700 consecutive patients of all ages were examined with the slit lamp during their routine eye clinic appointment. Patients with posterior embryotoxon were invited to return for full ocular examination including keratometry, corneal topography, and gonioscopy. In all, 49 out of 723 patients were found to have PE. This gives a prevalence of 6.8% with an age range of 18 months to 95 years. There was a higher prevalence in the younger age group of 22.5% (age range 18 months to 20 years) compared to 5.9% in the older age range (21–95 years). A total of 29 patients with PE returned for further examination. Six patients had glaucoma (two with Axenfeld's syndrome and one with aniridia), and one had ocular hypertension. In all, 20 patients had bilateral PE on slit-lamp examination, which increased to 24 with gonioscopy. The majority of the PE was seen temporally (97.9%) and limited to a few clock hours. Gonioscopy showed that eight patients with PE had associated inferior pigmentation of schwalbes line. This large series found the prevalence of PE the general ophthalmic clinic to be 6.8%. Its presence should prompt careful anterior segment examination, including gonioscopy, to identify any associated abnormalities that may carry a risk of glaucoma. Children should also be assessed for any associated systemic or genetic abnormality.

Targeted delivery of intravenously administered genetically altered cells or stem cells is still in an early stage of investigation. We developed a method of delivering iron oxide (ferumoxide)-labeled mesenchymal stem cells (MSCs) to a targeted area in an animal model by applying an external magnet. Rats with or without an external magnet placed over the liver were injected intravenously with ferumoxide-labeled MSCs and magnetic resonance imaging (MRI) signal intensity (SI) changes, iron concentration, and concentration of MSCs in the liver were monitored at different time points. SI decreased in the liver after injection of MSCs and returned gradually to that of control rat livers at approximately day 29. SI decreases were greater in rats with external magnets. Higher iron concentration and increased labeled cell numbers were detected in rat livers with external magnets. The external magnets influenced the movement of labeled MSCs such that the cells were retained in the region of interest. These results potentially open a new area of investigation for delivering stem cells or genetically altered cells.

Optical computed tomography (CT) is physically similar to x-ray CT but is more versatile since many powerful light sources exist and optical elements such as mirrors, lenses, polarizers and efficient detectors are available. There are many potential forms of optical CT. Attenuation, fluorescence or scatter, polarization and refractive index spatial changes are all examples of optical CT. To date, optical CT for gel dosimetry has been limited to attenuation measurements that are the sum of scatter and absorption along defined lines. Polymerization gels turn white with absorbed dose and attenuation is due to scatter. Radiochromic gels also form a dose image due to changes in visible absorption. This short review concentrates on the papers published since the DOSGEL 2001 meeting and highlights experimental results and issues that are important for obtaining good quality input data for reconstruction. The format involves selected highlights from the papers and associated points from our experience with optical CT experimentation. The comments are intended to assist researchers unfamiliar with optical measurements to obtain high quality transmission data, a necessary step in quantitative gel dosimetry.