The Incidence of Complications Following Scarf Osteotomy for the Treatment of Hallux Valgus: A Systematic Review With Meta-Analysis.

The Scarf osteotomy is a surgical procedure performed to correct a hallux valgus deformity. Multiple studies have supported use of the procedure with favorable outcomes. In contrast, there have been studies showing a significant complication rate with the procedure. Incidence of complications remains underreported in the literature. We performed a systemic review and meta-analysis examining a wide range of reported complications and associated clinical outcomes from the Scarf osteotomy. One hundred and sixteen publications were identified and 25 (21.6%) met our inclusion criteria. A total of 1583 Scarf procedures were included. Weighted mean follow-up was 26.4 months [range 12-168 months]. We found a 5.1% rate of recurrence, 3.5% rate of troughing, 1.0% rate of avascular necrosis, 1.8% rate of nonunion, 2.7% rate of malunion, 2.4% rate of infection, 5.3% rate of complex regional pain syndrome, and 3.4% rate of hallux varus. An average decrease in intermetatarsal angle of 6.3° was observed. No statistical difference was found in outcomes when comparing Scarf versus Scarf with additional procedure performed at time of surgery. To our knowledge, this systematic review and meta-analysis contains the highest number of Scarf procedures analyzed and presents complication rates on multiple adverse outcomes.

Measurement of Lepton-Jet Correlation in Deep-Inelastic Scattering with the H1 Detector Using Machine Learning for Unfolding.

The first measurement of lepton-jet momentum imbalance and azimuthal correlation in lepton-proton scattering at high momentum transfer is presented. These data, taken with the H1 detector at HERA, are corrected for detector effects using an unbinned machine learning algorithm (multifold), which considers eight observables simultaneously in this first application. The unfolded cross sections are compared with calculations performed within the context of collinear or transverse-momentum-dependent factorization in quantum chromodynamics as well as Monte Carlo event generators.

Phenomenological Constraints on the Transport Properties of QCD Matter with Data-Driven Model Averaging.

Using combined data from the Relativistic Heavy Ion and Large Hadron Colliders, we constrain the shear and bulk viscosities of quark-gluon plasma (QGP) at temperatures of ∼150-350 MeV. We use Bayesian inference to translate experimental and theoretical uncertainties into probabilistic constraints for the viscosities. With Bayesian model averaging we propagate an estimate of the model uncertainty generated by the transition from hydrodynamics to hadron transport in the plasma's final evolution stage, providing the most reliable phenomenological constraints to date on the QGP viscosities.

Case Report: Brachial Neuritis in a Patient with Epstein Barr Virus.

A 41 year-old man, recently returned from Thailand, presented with bilateral shoulder pain and weakness, fever greater than 38 degrees and coryzal symptoms. He had no significant past medical history. He had abnormal liver function tests and an abnormal electromyogram of his right upper limb. He was diagnosed with acute Epstein Barr virus infection, however cerebrospinal fluid was negative for the virus. At follow up after three months, the patient had persistent weakness of his right upper limb. The literature suggests neurological features present in up to 7.5% of patients with Epstein Barr virus, although argues this is underestimated with the virus often being overlooked as a cause of neurological symptoms.

Utility of 18F-fluoroestradiol (18F-FES) PET/CT imaging as a pharmacodynamic marker in patients with refractory estrogen receptor-positive solid tumors receiving Z-endoxifen therapy.

BACKGROUND: Z-endoxifen is the most potent of the metabolites of tamoxifen, and has the potential to be more effective than tamoxifen because it bypasses potential drug resistance mechanisms attributable to patient variability in the expression of the hepatic microsomal enzyme CYP2D6. 18F-FES is a positron emission tomography (PET) imaging agent which selectively binds to estrogen receptor alpha (ER-α) and has been used for non-invasive in vivo assessment of ER activity in tumors. This study utilizes 18F-FES PET imaging as a pharmacodynamic biomarker in patients with ER+ tumors treated with Z-endoxifen. METHODS: Fifteen patients were recruited from a parent therapeutic trial of Z-endoxifen and underwent imaging with 18F-FES PET at baseline. Eight had positive lesions on the baseline scan and underwent follow-up imaging with 18F-FES 1-5 days post administration of Z-endoxifen. RESULTS: Statistically significant changes (p = 0.0078) in standard uptake value (SUV)-Max were observed between the baseline and follow-up scans as early as 1 day post drug administration. CONCLUSION: F-FES PET imaging could serve as a pharmacodynamic biomarker for patients treated with ER-directed therapy.

Randomized trial of a dual-hormone artificial pancreas with dosing adjustment during exercise compared with no adjustment and sensor-augmented pump therapy.

AIMS: To test whether adjusting insulin and glucagon in response to exercise within a dual-hormone artificial pancreas (AP) reduces exercise-related hypoglycaemia. MATERIALS AND METHODS: In random order, 21 adults with type 1 diabetes (T1D) underwent three 22-hour experimental sessions: AP with exercise dosing adjustment (APX); AP with no exercise dosing adjustment (APN); and sensor-augmented pump (SAP) therapy. After an overnight stay and 2 hours after breakfast, participants exercised for 45 minutes at 60% of their maximum heart rate, with no snack given before exercise. During APX, insulin was decreased and glucagon was increased at exercise onset, while during SAP therapy, subjects could adjust dosing before exercise. The two primary outcomes were percentage of time spent in hypoglycaemia (<3.9 mmol/L) and percentage of time spent in euglycaemia (3.9-10 mmol/L) from the start of exercise to the end of the study. RESULTS: The mean (95% confidence interval) times spent in hypoglycaemia (<3.9 mmol/L) after the start of exercise were 0.3% (-0.1, 0.7) for APX, 3.1% (0.8, 5.3) for APN, and 0.8% (0.1, 1.4) for SAP therapy. There was an absolute difference of 2.8% less time spent in hypoglycaemia for APX versus APN (p = .001) and 0.5% less time spent in hypoglycaemia for APX versus SAP therapy (p = .16). Mean time spent in euglycaemia was similar across the different sessions. CONCLUSIONS: Adjusting insulin and glucagon delivery at exercise onset within a dual-hormone AP significantly reduces hypoglycaemia compared with no adjustment and performs similarly to SAP therapy when insulin is adjusted before exercise.

Economic consequences incurred by living kidney donors: a Canadian multi-center prospective study.

Some living kidney donors incur economic consequences as a result of donation; however, these costs are poorly quantified. We developed a framework to comprehensively assess economic consequences from the donor perspective including out-of-pocket cost, lost wages and home productivity loss. We prospectively enrolled 100 living kidney donors from seven Canadian centers between 2004 and 2008 and collected and valued economic consequences ($CAD 2008) at 3 months and 1 year after donation. Almost all (96%) donors experienced economic consequences, with 94% reporting travel costs and 47% reporting lost pay. The average and median costs of lost pay were $2144 (SD 4167) and $0 (25th-75th percentile 0, 2794), respectively. For other expenses (travel, accommodation, medication and medical), mean and median costs were $1780 (SD 2504) and $821 (25th-75th percentile 242, 2271), respectively. From the donor perspective, mean cost was $3268 (SD 4704); one-third of donors incurred cost >$3000, and 15% >$8000. The majority of donors (83%) reported inability to perform usual household activities for an average duration of 33 days; 8% reported out-of-pocket costs for assistance with these activities. The economic impact of living kidney donation for some individuals is large. We advocate for programs to reimburse living donors for their legitimate costs.

Male breast cancer, age and sex chromosome aneuploidy.

BACKGROUND: In cultured, dividing transformed T lymphocytes and in dividing bone marrow cells from normal men and those with a haematological malignancy, sex chromosome aneuploidy has been found to increase in prevalence and degree with age. This has rarely been investigated in non-dividing uncultured blood samples. The loss and gain of the X chromosome in dividing transformed lymphocytes in women with age is much more frequent than that of the Y chromosome in males. However, paradoxically X chromosome aneuploidy is rarely seen in the dividing cells of bone marrow of females. METHODS: In blood samples from 565 men with breast cancer and 54 control men from the England and Wales general population, 80 cell nuclei per sample were scored for presence of X and Y chromosomes using fluorescent centromeric probes. RESULTS: Sex chromosome aneuploidy, largely Y chromosome loss, was present in 63% of cases and 57% of controls, with the prevalence and degree of aneuploidy increasingly sharply and highly significantly with age. At ages 65-80 years, 71% of cases and 85% of controls showed aneuploidy and 15% and 25%, respectively, had ≥ 10% of cells aneuploid. Allowing for age, aneuploidy was less prevalent (P=0.03) in cases than controls. CONCLUSION: Sex chromosome aneuploidy in non-dividing nuclei of peripheral blood cells is frequent in adult men, the prevalence and degree increasing sharply with age. The possible relation of sex chromosome aneuploidy to breast cancer risk in men, and to cancer risk generally, needs further investigation, ideally in cohort studies.

Nasal carriage of Streptococcus pneumoniae serotypes and Staphylococcus aureus in Streptococcus pneumoniae-vaccinated and non-vaccinated young children.

Since the implementation of Streptococcus pneumoniae (SPn) conjugate vaccination (PCV), non-vaccine types have prevailed in invasive pneumococcal disease (IPD), and an increase in Staphylococcus aureus (SA) burden has been suggested. Here, we assess the epidemiology of SA and SPn nasal carriage in 620 children at day-care centres; 141 of these children had received 1-4 PCV7 doses. A higher vaccine dosage was associated with non-vaccine-type SPn carriage. Of all SPn isolates, 45% were PCV7 types, 1% were additional PCV10 types and 22% were the three additional PCV13 types. SA carriage was inversely associated with vaccine-type SPn carriage. SPn serotype 19A showed higher SA co-carriage rates compared to other SPn serotypes. PCV7 implementation does not prevent children from being part of the IPD-related SPn transmission chain. These results contribute to the monitoring of SA- and SPn-related disease and add to the debate on the current national vaccination policy that recently included a change from PCV7 to PCV10.

Somatic c-KIT activating mutation in urticaria pigmentosa and aggressive mastocytosis: establishment of clonality in a human mast cell neoplasm.

Mastocytosis is characterized by accumulations of mast cells in various organs (1). Most cases are indolent and confined to the skin, where discrete mast cell infiltrates are associated increased epidermal melanin, a clinical picture known as urticaria pigmentosa (UP). Other forms of mastocytosis combine UP with aggressive involvement of other organs or with haemotologic abnormalities (1-4). It is not known whether all forms of mastocytosis are true neoplasms or whether some might represent reactive hyperplasias (5-7). The c-KIT proto-oncogene encodes a type III receptor tyrosine kinase (KIT) that is critical to the development and survival of mast cells and melanocytes (8-11). The ligand for KIT (KL) can stimulate mast cell development, proliferation, and mediator release (9,12-17), as well as melanocyte proliferation and pigment production (18-20). To determine the role of c-KIT in the pathogenesis of mastocytosis, we examined tissue and cells isolated from a patient with UP and aggressive systemic mastocytosis with massive splenic involvement. We found a mutation that results in constitutive activation and expression of c-KIT in mast cells of both skin and spleen. This is the first in situ demonstration of an activation c-KIT mutation in neoplastic cells. It also demonstrates the clonal and neoplastic nature of this form of mastocytes.

Positive effect of a simplified diet on blood phenylalanine control in different phenylketonuria variants, characterized by newborn BH4 loading test and PAH analysis.

Until today, the mainstay of phenylketonuria (PKU) treatment is a phenylalanine (Phe)-restricted diet. Strict dietary treatment decreases flexibility and autonomy and still has a major impact on patients and their families. Compliance is often poor, particularly in adolescence. The aim of this study was to investigate the effect of the intake of fruits and vegetables containing Phe less than 100 mg/100g ('simplified diet'), as recommended by WHO for all individuals, instead of classical totally restricted diet on the course and treatment control of the disease in a well-characterized PKU cohort (n=80). All individual blood Phe measurements of each patient (1992-2009) were statistically analyzed before and after diet switch. Epidemiological data, age at diagnosis, PAH mutations, BH(4) responsiveness, as well as Phe control measurements and detailed diet information were tabulated in a local database. 62.5% had BH4 loading test and 40% had PAH analysis; 50/80 switched from classical to simplified diet, including 26 classical PKU, 13 moderate PKU, 7 mild PKU and 4 mild hyperphenylalaninemia (HPA). Median Phe levels on a simplified diet did not differ significantly to the median Phe levels on classical diet in all disease groups. Our results indicate that a simplified diet has no negative effect on blood Phe control in patients with hyperphenylalaninemia, independent of severity of the phenotype or the age at diet switch, over the period of 3 years. Thus, a simpler approach to dietary treatment of PKU available to all HPA patients is more likely to be accepted and adhered by patients and might also increase quality of life.

Failure after soft-tissue release with tendon transfer for flexible iatrogenic hallux varus: a systematic review.

Hallux valgus is a common forefoot pathology often requiring surgical intervention for symptomatic relief. One complication of hallux valgus correction is flexible hallux varus. Iatrogenic flexible hallux varus often requires surgical repair; however, the most advantageous surgical procedure for repair of iatrogenic flexible hallux varus and their sustainability remains unclear. Therefore, we performed a systematic review to determine the sustainability of soft-tissue release with tendon transfer for the correction of iatrogenic flexible hallux varus. Studies were eligible for inclusion only if they involved failure of soft-tissue release with tendon transfer for flexible iatrogenic hallux varus. Eight studies met our inclusion criteria, seven of which were evidence-based medicine level IV studies and one was level V. A total of 52 patients, all female, involving 68 feet, were included. All studies included soft-tissue release of the first metatarsal-phalangeal joint capsule and 1 of the following procedures: Johnson transfer of the extensor hallucis longus tendon with arthrodesis of the hallux interphalangeal joint (41 feet); Hawkins transfer of the abductor hallucis tendon (9 feet); reverse Hawkins transfer (7 feet); Valtin transfer of the first dorsal interosseous tendon (7 feet); and Myerson transfer of the extensor hallucis brevis tendon (4 feet). The weighted mean age of the patients was 50.4 years, and the weighted mean follow-up was 30.2 months. A total of 11 complications (16.2%) occurred. Of note, only 3 cases (4.4%) of recurrent hallux varus deformity developed, all of which occurred after Johnson transfer of the extensor hallucis longus tendon, with arthrodesis of the hallux interphalangeal joint. Our results support that sustainable correction of iatrogenic flexible hallux varus can be achieved with soft-tissue release of the first metatarsal-phalangeal joint combined with a variety of tendon transfer procedures. However, given the limited data available, potential areas for additional prospective investigation remain.

Metabolism and excretion of asenapine in healthy male subjects.

The metabolism and excretion of asenapine [(3aRS,12bRS)-5-chloro-2-methyl-2,3,3a,12b-tetrahydro-1H-dibenzo[2,3:6,7]-oxepino [4,5-c]pyrrole (2Z)-2-butenedioate (1:1)] were studied after sublingual administration of [(14)C]-asenapine to healthy male volunteers. Mean total excretion on the basis of the percent recovery of the total radioactive dose was ∼90%, with ∼50% appearing in urine and ∼40% excreted in feces; asenapine itself was detected only in feces. Metabolic profiles were determined in plasma, urine, and feces using high-performance liquid chromatography with radioactivity detection. Approximately 50% of drug-related material in human plasma was identified or quantified. The remaining circulating radioactivity corresponded to at least 15 very polar, minor peaks (mostly phase II products). Overall, >70% of circulating radioactivity was associated with conjugated metabolites. Major metabolic routes were direct glucuronidation and N-demethylation. The principal circulating metabolite was asenapine N(+)-glucuronide; other circulating metabolites were N-desmethylasenapine-N-carbamoyl-glucuronide, N-desmethylasenapine, and asenapine 11-O-sulfate. In addition to the parent compound, asenapine, the principal excretory metabolite was asenapine N(+)-glucuronide. Other excretory metabolites were N-desmethylasenapine-N-carbamoylglucuronide, 11-hydroxyasenapine followed by conjugation, 10,11-dihydroxy-N-desmethylasenapine, 10,11-dihydroxyasenapine followed by conjugation (several combinations of these routes were found) and N-formylasenapine in combination with several hydroxylations, and most probably asenapine N-oxide in combination with 10,11-hydroxylations followed by conjugations. In conclusion, asenapine was extensively and rapidly metabolized, resulting in several regio-isomeric hydroxylated and conjugated metabolites.

Trans-obturator tape compared with tension-free vaginal tape in the surgical treatment of stress urinary incontinence: a cost utility analysis.

OBJECTIVE: To conduct an economic evaluation of the use of trans-obturator tape (TOT) compared with tension-free vaginal tape (TVT) in the surgical treatment of stress urinary incontinence (SUI) in women. DESIGN: Cost utility analysis from public-payer perspective, conducted alongside a randomised clinical trial (RCT). SETTING: Health services provided in Alberta, Canada. POPULATION: A total of 194 women who participated in the RCT, followed to 1 year from surgery. METHODS: Data collected on all women in the RCT, over 12 months following surgery. Comparisons undertaken between RCT groups for cost and quality-adjusted life-years (QALYs). Multiple imputation used for the 10% missing data. Bootstrapping used to account for sampling uncertainty. One-way sensitivity analysis conducted for productivity loss due to time away from work. MAIN OUTCOME MEASURES: Utility--15D questionnaire was used to calculate QALYs. Costs over 12 months--from trial data, health provider and provincial ministry of health. RESULTS: The TOT group had a non-significant average saving of $1133 (95% CI -2793; 442), with no difference in average QALYs between groups (95% CI -0.02; 0.01). TOT was cost-saving in over 80% of bootstrapping replications, over a wide range of willingness-to-pay. CONCLUSION: The bootstrapping replication results suggest that TOT could be cost-effective compared with TVT in the treatment of SUI. However, these results must be confirmed by longer-term assessment of clinical and economic outcomes, because of concern that surgical tape palpable at 12 months may lead to vaginal erosion and further treatment.

Impact of the HIV epidemic and Anti-Retroviral Treatment policy on lymphoma incidence and subtypes seen in the Western Cape of South Africa, 2002-2009: preliminary findings of the Tygerberg Lymphoma Study Group.

The Tygerberg Lymphoma Study Group was constituted in 2007 to quantify the impact of HIV on the pattern and burden of lymphoma cases in the Western Cape of South Africa which currently has an HIV prevalence of 15%. South Africa has had an Anti-Retroviral Treatment (ART) policy and a roll-out plan since 2004 attaining 31% effective coverage in 2009. This study is designed to qualify and establish the impact of HIV epidemic and the ARV roll-out treatment program on the incidence of HIV Related Lymphoma (HRL). Early data document that despite the ART roll out, cases of HRL are increasing in this geographical location, now accounting for 37% of all lymphomas seen in 2009 which is an increase from 5% in 2002. This is in contrast to trends seen in developed environments following the introduction of ART. Also noted are the emergence of subtypes not previously seen in this location such as Burkitt and plasmablastic lymphomas. Burkitt lymphoma is now the commonest HRL seen in this population followed by diffuse large B-cell lymphoma subtypes. The reasons for this observed increase in HRL are not ascribable to improved diagnostic capacity as the tertiary institute in which these diagnoses are made has had significant expertise in this regard for over a decade. We ascribe this paradoxical finding to an ART treatment environment that is ineffective for a diversity of reasons, paramount of which are poor coverage, late commencement of ART and incomplete viral suppression.

Self-mixing flow sensor using a monolithic VCSEL array with parallel readout.

The self-mixing sensing technique is a compact, interferometric sensing technique that can be used for measuring fluid flows. In this work, we demonstrate a parallel readout self-mixing flow velocity sensing system based on a monolithic Vertical-Cavity Surface-Emitting Laser (VCSEL) array. The parallel sensing scheme enables high-resolution full-field imaging systems employing electronic scanning with faster acquisition rates than mechanical scanning systems. The self-mixing signal is acquired from the variation in VCSEL junction voltage, thus markedly reducing the system complexity. The system was validated by measuring velocity distribution of fluid in a custom built diverging-converging planar flow channel. The results obtained agree well with simulation and demonstrate the feasibility of high frame-rate and resolution parallel self-mixing sensors.

The PROgnostic Value of unrequested Information in Diagnostic Imaging (PROVIDI) Study: rationale and design.

We describe the rationale for a new study examining the prognostic value of unrequested findings in diagnostic imaging. The deployment of more advanced imaging modalities in routine care means that such findings are being detected with increasing frequency. However, as the prognostic significance of many types of unrequested findings is unknown, the optimal response to such findings remains uncertain and in many cases an overly defensive approach is adopted, to the detriment of patient-care. Additionally, novel and promising image findings that are newly available on many routine scans cannot be used to improve patient care until their prognostic value is properly determined. The PROVIDI study seeks to address these issues using an innovative multi-center case-cohort study design. PROVIDI is to consist of a series of studies investigating specific, selected disease entities and clusters. Computed Tomography images from the participating hospitals are reviewed for unrequested findings. Subsequently, this data is pooled with outcome data from a central population registry. Study populations consist of patients with endpoints relevant to the (group of) disease(s) under study along with a random control sample from the cohort. This innovative design allows PROVIDI to evaluate selected unrequested image findings for their true prognostic value in a series of manageable studies. By incorporating unrequested image findings and outcomes data relevant to patients, truly meaningful conclusions about the prognostic value of unrequested and emerging image findings can be reached and used to improve patient-care.

Human T-cell leukemia virus (HTLV-I) antibodies in Africa.

Antibodies specific for human T-cell leukemia-lymphoma virus type I (HTLV-I) were demonstrated in serum samples from various groups of people in South Africa, Uganda, Ghana, Nigeria, Tunisia, and Egypt. The samples had been collected for other purposes and were presumably selected without bias toward clinical conditions associated with HTLV infections. Regional differences in antibody positivity were observed, indicating widely distributed loci of occurrence of HTLV on the African continent in people of both black and white ancestry. Two patients with high titers of antibody to HTLV-I had some signs of adult T-cell leukemia-lymphoma. In several groups a high frequency of false positive serum reactions was indicated when specific confirmation steps were included in the assay. Further characterization of these sera revealed highly elevated immunoglobulin levels, possibly due to polyclonal activation of immunoglobulin synthesis in these subjects. The possibility that related cross-reactive human retroviruses coexist in the same groups was not eliminated.