Prognosis of trochanteric pain in primary care

BACKGROUND: Trochanteric pain is the second most important diagnosis of hip problems presenting in primary care, but its incidence and prognosis in this context is largely unknown. AIM: To determine the 1- and 5-year prognoses of trochanteric pain and the predictive variables for consistent complaints. DESIGN OF THE STUDY: Retrospective cohort study. SETTING: One hundred and sixty-four patients (mean age = 55 years, 80% female) with incidental trochanteric pain in the years 1996 or 2000 were asked in 2001 for past and present symptoms of trochanteric pain. Therapeutic interventions, demographic factors and comorbidity were also investigated. METHOD: The databases of 39 GPs were screened in order to identify all incident cases with a suspicion of trochanteric pain in the years 1996 or 2000. These cases were sent a questionnaire. RESULTS: The incidence of trochanteric pain in primary care is 1.8 patients per 1000 per year. After 1 year at least 36% still suffered from trochanteric pain, and after 5 years this was 29%. Patients with osteoarthritis (OA) in the lower limbs had a 4.8-fold risk of persistent symptoms after 1 year, as compared to patients without OA. Patients who had received a corticosteroid injection had a 2.7-fold chance of recovery after 5 years, as compared with patients who had not received an injection. CONCLUSION: Trochanteric pain is shown to be a chronic disease in a substantial number of patients. The disorder is associated with much impairment when conducting daily activities.     

The whole leg radiograph

The whole leg radiograph (WLR), the standard technique for determining axial alignment, is usually taken in a standing position, although some prefer the supine position. To determine the difference between these two positions, we performed a standing and a supine WLR in 20 patients with a varus alignment. We found an average of 2 degrees more varus deviation in the standing position than in the supine position.     

Antitumor immune response by CX3CL1 fractalkine gene transfer depends on both NK and T cells

The CX3C chemokine fractalkine (CX3CL1) exists as both a membrane-bound form promoting firm cell-cell adhesion and a soluble form chemoattracting leukocytes expressing its receptor CX3CR1. When adenoviral vector expressing mouse fractalkine (AdFKN) was transduced to the tumor cells, fractalkine was expressed as both membrane-bound form on the tumor cells and soluble form in the supernatant in vitro. Intratumoral injection of AdFKN (1 x 10(9)PFU/tumor) into C26 and B16F10 tumors resulted in marked reduction of tumor growth compared to control (C26: 86.5%, p<0.001; B16F10: 85.5%, p<0.001). Histological examination of tumor tissues revealed abundant infiltration of NK cells, dendritic cells, and CD8(+) T lymphocytes 3 and/or 6 days after treatment with AdFKN. Splenocytes from mice treated by AdFKN developed tumor-specific cytotoxic T cells, and thereby protected from rechallenging with parental tumor cells. Antitumor effects by AdFKN were completely abrogated in both NK cell-depleted mice and CD8(-/-) mice, and partially blocked in CD4(-/-) mice. These data indicated that fractalkine mediates antitumor effects by both NK cell-dependent and T cell-dependent mechanisms. This study suggests that fractalkine can be a suitable candidate for immunogene therapy of cancer because fractalkine induces both innate and adaptive immunity.     

Decision and forecast horizons in a stochastic environment: A survey

This paper constructs a unified framework to survey most of the work done to date on decision

1 decision horizon replaces the term planning horizon used in the literature in the context of this paper. This is done because of an alternate and more popular use of the term planning horizon as simply the given length of the horizon in a finite horizon problem.

and forecast horizons in a stochastic environment. The paper is divided into sections by type of model. For each model type, the issues of existence of these horizons and of derivation of sufficient conditions for their determination are studied. Appropriate examples are presented.     

Structural spinal abnormalities on MRI and associations with weight status in a general pediatric population

BACKGROUND CONTEXTSeveral spinal abnormalities have been studied using magnetic resonance imaging (MRI). However, in children these studies were sparsely performed in general populations. Examining young children's spines is important since the shape of the bone is largely determined during the growth spurt. Furthermore, it is so far unknown if associations between weight status and spinal abnormalities, which are known for adolescents and adults, are already present in young children.PURPOSEWe aimed to present the prevalence of structural abnormalities in the prepubertal pediatric spine on MRI and their association with measures of the children's body weight and body composition.STUDY DESIGNCross-sectional study embedded in a prospective population-based birth cohort study.PATIENT SAMPLEFor this study, participants from the Generation R Study were selected based on the availability of MRI data of the lumbar spine and accelerometry data at the age of 9 years.OUTCOME MEASURESThe presence of structural abnormalities of intervertebral discs and vertebrae was scored on MRI. The body mass index-standard deviation [BMI-SD] score was calculated from objectively measured weight and height, and body composition measurements were obtained by a dual-energy X-ray absorptiometry scan.METHODSA semiquantitative scoring tool to assess the intervertebral discs and vertebrae of the lumbar spine on conventional MRI was designed for this purpose. Proportions of children with spinal abnormalities on at least one lumbar vertebral level were presented. Logistic regression was used to analyze associations between abnormalities and weight and body composition. We declare not to have any financial conflicts of interests.RESULTSWe included 559 children (median age of 9.88 years (interquartile range 6.74–10.02), 48.5% boys). Most frequently observed abnormalities of the intervertebral discs were abnormal signal intensity (24.9%), decreased or collapsed disc height (37.6%), disc bulging (73.3%), and abnormal nuclear shape (29.1%). Vertebral endplate irregularities and lumbosacral transitional vertebrae were seen in respectively 40% and 9.3% of the participants. Except for disc bulging, all abnormalities were predominantly present at the L5 level. Only the presence of endplate irregularities was associated with a higher body weight (BMI SD score (odds ratio [OR] 1.50 [95% confidence interval [CI] 1.21–1.86]) and BMI SD change (OR 1.48 [95% CI 1.07–2.03])) and increased body mass values in body composition measurements (% body fat (OR 1.05 [95% CI 1.02–1.09), fat mass index (OR 1.23 [95% CI 1.09–1.39]), and fat-free mass index (OR 1.30 [95% CI 1.06–1.59])) in adjusted analyses.CONCLUSIONSStructural spinal abnormalities, especially disc bulging, endplate irregularities, and an abnormal disc height, are already present in children aged 9 years from a Dutch population-based cohort. Of those abnormalities, endplate irregularities are associated with various weight and body composition measurements.     

Anti-SARS-CoV-2 activity of targeted kinase inhibitors: Repurposing clinically available drugs for COVID-19 therapy

Coronavirus disease 2019 (COVID-19) remains a major public health concern, and vaccine unavailability, hesitancy, or failure underscore the need for discovery of efficacious antiviral drug therapies. Numerous approved drugs target protein kinases associated with viral life cycle and symptoms of infection. Repurposing of kinase inhibitors is appealing as they have been vetted for safety and are more accessible for COVID-19 treatment. However, an understanding of drug mechanism is needed to improve our understanding of the factors involved in pathogenesis. We tested the in vitro activity of three kinase inhibitors against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including inhibitors of AXL kinase, a host cell factor that contributes to successful SARS-CoV-2 infection. Using multiple cell-based assays and approaches, gilteritinib, nintedanib, and imatinib were thoroughly evaluated for activity against SARS-CoV-2 variants. Each drug exhibited antiviral activity, but with stark differences in potency, suggesting differences in host dependency for kinase targets. Importantly, for gilteritinib, the amount of compound needed to achieve 90% infection inhibition, at least in part involving blockade of spike protein-mediated viral entry and at concentrations not inducing phospholipidosis (PLD), approached a clinically achievable concentration. Knockout of AXL, a target of gilteritinib and nintedanib, impaired SARS-CoV-2 variant infectivity, supporting a role for AXL in SARS-CoV-2 infection and supporting further investigation of drug-mediated AXL inhibition as a COVID-19 treatment. This study supports further evaluation of AXL-targeting kinase inhibitors as potential antiviral agents and treatments for COVID-19. Additional mechanistic studies are needed to determine underlying differences in virus response.     

Is Anesthetic Hip Joint Injection Useful in Diagnosing Hip Osteoarthritis? A Meta-Analysis of Case Series

To assess the diagnostic value of intra-articular anesthetic hip injection in patients with hip pain atypical for osteoarthritis (OA), literature was searched. Included were studies assessing the diagnostic value of anesthetic hip injections in differentiating between pain caused by OA or another source. Pooled estimates of sensitivity and specificity with 95% confidence intervals (CI) were calculated. Of the 1387 potentially eligible articles, nine case series with high risk of bias could be included. The pooled sensitivity was 0.97 (95% CI 0.87, 0.99). Specificity was 0.91 (95% CI 0.83, 0.95). For clinical practice, no recommendation can be made regarding the use of hip injections for diagnosing hip OA. High quality, accurately reported studies are needed to provide better evidence on the diagnostic role of hip injection.     

ALLYLAMINE AND-AMINOPROPIONITRILE-INDUCED VASCULAR INJURY: ENHANCED EXPRESSION OF HIGH-MOLECULAR-WEIGHT PROTEINS

In the present study we describe changes in aorta at the protein level associated with allylamine (AA) and-aminopropionitrile ( APN) induced vascular toxicity in a rat model. This model represents a remarkable synergistic, necrotizing toxic effect of these combined toxins, and our rationale was to examine protein expression in order to shed light on the mechanisms underlying this synergism. Rats were given AA (100 mg kg body weight day) and APN (1 g kg body weight day) by gavage for 10 d; this protocol has been shown to result in smooth-muscle necrosis, but no visible connective tissue changes. Soluble and insoluble fractions from AA APN- or from APN-treated aorta showed enhanced expression of three high-molecular-weight protein bands (ranges between approximately 120 and 95 kD). The time course of induction of proteins showed the appearance of AA APN-induced specific proteins at d 3 of AA APN treatment. Partial purification and characterization suggested that AA APN specific proteins are likely to be collagen proteins (type I). Thus, the data presented in this article help in understanding the vascular toxicity induced by AA APN or by APN, in that we have described an altered phenotypic expression of collagenous proteins indicative of selective medial vascular toxicity.