Validated image ordering guidelines for odontogenic infections.

Overuse of computed tomography (CT) is a prevalent problem across multiple disciplines in healthcare and is common in the workup of odontogenic infections. To address this problem, an imaging pathway was created through collaboration of the oral maxillofacial surgery and emergency medicine departments to reduce unnecessary CT orders. A prospective study was implemented to assess the success of the imaging pathway to guide in the selection of the most appropriate radiological imaging modality when managing an odontogenic infection. Subjects included were adults, presenting through the emergency department for confirmed odontogenic infection. The primary outcome was the rate of unnecessary CT scans performed after the introduction of the pathway. Statistics were performed via the t-test, χ2 test, and multiple regression analysis; P < 0.05 was considered significant. Between February 1 and December 15, 2019, 100 patients met the inclusion criteria and were enrolled. The rate of unnecessary CT scans was 25.6%, compared to 56.6% prior to the introduction of the imaging pathway. The pathway did not misclassify any patient to not receive a CT when it was medically necessary. Use of the imaging pathway has the potential to reduce unnecessary CT imaging for odontogenic infections, without negatively affecting patient outcomes.

Interferon-Induced Transmembrane Protein 1 Restricts Replication of Viruses That Enter Cells via the Plasma Membrane.

The acute antiviral response is mediated by a family of interferon-stimulated genes (ISGs), providing cell-intrinsic immunity. Mutations in genes encoding these proteins are often associated with increased susceptibility to viral infections. One family of ISGs with antiviral function is the interferon-inducible transmembrane proteins (IFITMs), of which IFITM3 has been studied extensively. In contrast, IFITM1 has not been studied in detail. Since IFITM1 can localize to the plasma membrane, we investigated its function with a range of enveloped viruses thought to infect cells by fusion with the plasma membrane. Overexpression of IFITM1 prevented infection by a number of Paramyxoviridae and Pneumoviridae, including respiratory syncytial virus (RSV), mumps virus, and human metapneumovirus (HMPV). IFITM1 also restricted infection with an enveloped DNA virus that can enter via the plasma membrane, herpes simplex virus 1 (HSV-1). To test the importance of plasma membrane localization for IFITM1 function, we identified blocks of amino acids in the conserved intracellular loop (CIL) domain that altered the subcellular localization of the protein and reduced antiviral activity. By screening reported data sets, 12 rare nonsynonymous single nucleotide polymorphisms (SNPs) were identified in human IFITM1, some of which are in the CIL domain. Using an Ifitm1-/- mouse, we show that RSV infection was more severe, thereby extending the range of viruses restricted in vivo by IFITM proteins and suggesting overall that IFITM1 is broadly antiviral and that this antiviral function is associated with cell surface localization.IMPORTANCE Host susceptibility to viral infection is multifactorial, but early control of viruses not previously encountered is predominantly mediated by the interferon-stimulated gene (ISG) family. There are upwards of 300 of these genes, the majority of which do not have a clearly defined function or mechanism of action. The cellular location of these proteins may have an important effect on their function. One ISG located at the plasma membrane is interferon-inducible transmembrane protein 1 (IFITM1). Here we demonstrate that IFITM1 can inhibit infection with a range of viruses that enter via the plasma membrane. Mutant IFITM1 proteins that were unable to localize to the plasma membrane did not restrict viral infection. We also observed for the first time that IFITM1 plays a role in vivo, and Ifitm1-/- mice were more susceptible to viral lung infection. These data contribute to our understanding of how ISGs prevent viral infections.

A phase II trial of lenalidomide plus rituximab in previously untreated follicular non-Hodgkin's lymphoma (NHL): CALGB 50803 (Alliance).

BACKGROUND: This multicenter, phase II trial tested the tolerability and efficacy of lenalidomide plus rituximab in patients with previously untreated follicular lymphoma (FL). PATIENTS AND METHODS: Patients with grade 1-3a FL, stage 3-4 or bulky stage 2, FL international prognostic index (FLIPI) 0-2, and no prior therapy were eligible to receive rituximab 375 mg/m2 weekly during cycle 1 and day 1 of cycles 4, 6, 8, and 10, plus lenalidomide 20-25 mg on days 1-21 for twelve 28-day cycles. The primary objectives were to evaluate response rates [complete (CR) and overall] and time to progression. Secondary objectives included toxicity, response according to polymorphisms in FcgR2A and FcgR3A, and changes in circulating pro-angiogenic cells. RESULTS: From October 2010 to September 2011, 66 patients were enrolled. Median age was 53 years, 34 were female, 15 had bulky disease, 21 were FLIPI 0-1, 43 FLIPI 2, and 2 FLIPI 3. One patient withdrew before receiving treatment. Fifty-one patients completed 12 cycles of lenalidomide. Reasons for discontinuation included withdrawal (n = 6), adverse events (n = 6), progression (n = 2). Grade 3-4 hematologic toxicity included neutropenia (21%), lymphopenia (9%), and thrombocytopenia (2%), infection (11%), and rash (8%). Grade 1-2 toxicity included fatigue (78%), diarrhea (37%), rash (32%), and febrile neutropenia in one patient. The overall response rate was 95%; the CR rate was 72% (95% confidence interval, 60% to 83%). With a median follow-up of 5 years, the 2- and 5-year progression-free survival were 86% and 70%, respectively, and the 5-year overall survival was 100%. There was no association between CR rate or PFS and FLIPI, histological grade, bulky disease, FcgR2A/FcgR3A polymorphism, or change in circulating endothelial cell/hematopoietic progenitor cell. CONCLUSION: Lenalidomide plus rituximab was associated with low rates of grade 3-4 toxicity, yielded a CR rate and PFS similar to chemotherapy-based treatment and may represent a reasonable alternative to immunochemotherapy in previously untreated FL. CLINICALTRIALS.GOV IDENTIFIER: NCT01145495.

Imaging, procedural and clinical variables associated with tumor yield on bone biopsy in metastatic castration-resistant prostate cancer.

BACKGROUND: Understanding the mechanisms driving disease progression is fundamental to identifying new therapeutic targets for the treatment of men with metastatic castration-resistant prostate cancer (mCRPC). Owing to the prevalence of bone metastases in mCRPC, obtaining sufficient tumor tissue for analysis has historically been a challenge. In this exploratory analysis, we evaluated imaging, procedural and clinical variables associated with tumor yield on image-guided bone biopsy in men with mCRPC. METHODS: Clinical data were collected prospectively from men with mCRPC enrolled on a phase II trial with serial metastasis biopsies performed according to standard clinical protocol. Imaging was retrospectively reviewed. We evaluated the percent positive biopsy cores (PPC), calculated as the number of positive cores divided by the total number of cores collected per biopsy. RESULTS: Twenty-nine men had 39 bone biopsies. Seventy-seven percent of bone biopsies had at least one positive biopsy core. We determined that lesion size and distance from the skin to the lesion edge correlated with tumor yield on biopsy (median PPC 75% versus 42% for lesions >8.8 cm(3) versus ⩽ 8.8 cm(3), respectively, P=0.05; median PPC 33% versus 71% for distance ⩾ 6.1 versus <6.1 cm, respectively, P = 0.02). There was a trend towards increased tumor yield in patients with increased uptake on radionuclide bone scan, higher calcium levels and shorter duration of osteoclast-targeting therapy, although this was not statistically significant. Ten men had 14 soft tissue biopsies. All soft tissue biopsies had at least one positive biopsy core. CONCLUSIONS: This exploratory analysis suggests that there are imaging, procedural and clinical variables that have an impact on image-guided bone biopsy yield. In order to maximize harvest of prostate cancer tissue, we have incorporated a prospective analysis of the metrics described here as part of a multi-institutional project aiming to use the molecular characterization of mCRPC tumors to direct individual therapy.

Brentuximab vedotin does not cause clinically relevant QTc interval prolongation in patients with CD30-positive hematologic malignancies.

PURPOSE: Brentuximab vedotin (ADCETRIS®), an antibody-drug conjugate, comprises an anti-CD30 antibody conjugated by a protease-cleavable linker to a microtubule-disrupting agent, monomethyl auristatin E (MMAE). In vitro studies showed that MMAE does not interfere with hERG K+ channels at clinically relevant concentrations. In pivotal phase 2 clinical trials in patients with relapsed or refractory Hodgkin lymphoma and systemic anaplastic large cell lymphoma, brentuximab vedotin has shown substantial efficacy and an acceptable safety profile. This phase 1 open-label study was designed to evaluate the effect of brentuximab vedotin on the duration of cardiac ventricular repolarization. METHODS: Patients with CD30-positive hematologic malignancies were treated with 1.8 mg/kg brentuximab vedotin by intravenous infusion every 3 weeks for up to 16 cycles. The primary endpoint was the change from baseline to Cycle 1 Days 2, 3, and 4 in the duration of ventricular repolarization using Fridericia's corrected QT interval (QTcF). RESULTS: There was no clinically meaningful change from baseline in the duration of ventricular repolarization as measured by QTcF in the 46 evaluable patients out of 52 total patients treated with brentuximab vedotin. There was no evidence of treatment-emergent cardiac safety abnormalities. Brentuximab vedotin was generally well tolerated with a response rate and an adverse event profile consistent with prior studies. CONCLUSION: There is no significant prolongation of the QT/QTc interval with brentuximab vedotin in patients with CD30-positive hematologic malignancies.

The association between body mass index and musculoskeletal foot disorders: a systematic review.

The primary aim of this systematic review was to investigate the relationship between body mass index (BMI) and foot disorders. The secondary aim was to investigate whether weight loss is effective for reducing foot pain. Five electronic databases (Ovid MEDLINE, Ovid EMBASE, Ovid AMED, CINAHL and The Cochrane Library) and reference lists from relevant papers were searched in April 2011. Twenty-five papers that reported on the association between BMI and musculoskeletal foot disorders met our inclusion criteria and were reviewed. The evidence indicates: (i) a strong association between increased BMI and non-specific foot pain; and (ii) a strong association between increased BMI and chronic plantar heel pain in a non-athletic population. The evidence is inconclusive regarding the relationship between BMI and the following specific disorders of the foot; hallux valgus, tendonitis, osteoarthritis and flat foot. With respect to our second aim, there were only two prospective cohort studies that reported a reduction in foot symptoms following weight loss surgery. In summary, increased BMI is strongly associated with non-specific foot pain in the general population and chronic plantar heel pain in a non-athletic population. However, there is currently limited evidence to support weight loss to reduce foot pain.

Isolated lower extremity metastases, 9 years after initial diagnosis of retinoblastoma.

We report the development of isolated lower extremity metastases, in a child, 9 years after her initial diagnosis and treatment of bilateral infantile retinoblastomas. The radiographic, scintigraphic, computed tomographic, and magnetic resonance imaging findings are discussed. The dominant metastatic focus was blastic, involving the medial cuneiform. Additional occult lesions were found in the base of the second metatarsal, middle cuneiform, navicular and tibial diaphysis. An open biopsy confirmed the diagnosis. The occurrence of late distant metastases is rare in the USA.

Are routine iron stains on bone marrow trephine biopsy specimens necessary?

AIMS: To determine the role of Perls' staining in bone marrow trephine biopsy sections. METHODS: The haemosiderin content of 155 Perls' stained, formic acid decalcified trephine biopsy sections was assessed and compared with Perls' stained aspirate samples in 105 cases and haematoxylin and eosin (H&E) stained biopsy sections in all cases. RESULTS: An evaluable aspirate film with positive iron or at least seven negative particles was available for 105 biopsies. Only 71 of 95 cases with detectable aspirate iron had haemosiderin detectable on a Perls' stained section. None of 10 samples with a negative aspirate had a positive trephine biopsy. Haemosiderin was positive in 101 of the 155 Perls' stained sections, and was detectable on the H&E stained section in 71 of these cases. In five of 54 cases with negative Perls' staining, a small amount of haemosiderin was thought to be present on H&E staining. CONCLUSIONS: Aspirate smears reflect bone marrow iron stores more reliably than formic acid decalcified trephine biopsy sections. The presence of iron in Perls' stained aspirates in 44% of cases with negative Perls' stained sections indicates that iron is often lost from sections during decalcification. However, 61% of cases with unassessable aspirate samples had a positive trephine biopsy Perls' stain, contributing useful clinical information about iron status. Preparation of Perls' stained sections only in cases in which aspirate samples are inadequate for iron assessment and no obvious haemosiderin is present in an H&E stained section could produce savings in staff time and reagent costs.

How should stainable iron in bone marrow films be assessed?

AIMS: To identify how many particles should be examined to enable a confident assessment of the presence or absence of iron stores and the quantity of iron in a bone marrow aspirate to be made. METHODS: One hundred and ninety consecutive bone marrow aspirate samples were stained with Perls' stain and the iron content of 10 consecutive particles was recorded. The first particle found to be positive and the particle that was most positive were also noted. RESULTS: A minimum of seven particles must be examined to establish the absence of stainable iron. A minimum of nine particles must be reviewed to see the maximum iron stores in 100% of samples and therefore make a valid judgment of whether iron stores are reduced, normal, or increased. By these criteria, 46% of the samples tested here could not be optimally assessed for absence of iron or maximum iron stores. CONCLUSIONS: The sensitivity of examination of bone marrow aspirates for iron stores can be optimised by increasing the number of particles reviewed to seven or more. This may require the staining of additional slides.

Do iron plaque and genotypes affect arsenate uptake and translocation by rice seedlings (Oryza sativa L.) grown in solution culture?

The effects of Fe concentrations in the pretreatment solution on the induction of plaque and the differences between genotypes on arsenate uptake by and translocation within rice seedlings grown in nutrient solution in the greenhouse were investigated. After iron plaque on rice roots was induced in solutions containing 20, 40, 60, 80, and 100 mg Fe2+ l(-1), seedlings were transplanted into nutrient solution with 0.5 mg As l(-1). The formation of iron plaque was clearly visible as a reddish coating on the root surface after 12 h induction. Fe2+ concentrations in the pretreatment solution and 0.5 mg As l(-1) in the treatment solutions did not significantly affect rice growth. There was a significant correlation between the concentrations of Fe and As in iron plaque on the root surface for the three genotypes. About 75-89% of total As was concentrated in iron plaque (DCB-extracts). There were no significant differences in As concentrations in the roots between the three genotypes; however, As concentrations in shoots differed significantly between them. Arsenic concentrations in shoots were positively correlated with iron concentrations in the shoots. The results suggest that iron plaque may act as a 'buffer' for As in the rhizosphere.

Genotypic and phenotypic heterogeneity in familial microcoria.

AIMS: To describe the clinical features and genetic findings in two families presenting with microcoria inherited as an autosomal dominant trait. METHODS: Both affected and unaffected members of two families displaying familial microcoria were examined. Flash photography or infrared pupillography were used to assess pupils, and a full ophthalmic examination including visual acuity and field testing, refraction, biomicroscopy of anterior and posterior segments, and measurement of intraocular pressure were performed. DNA from the blood of affected and unaffected family members was investigated using standard markers to look for a possible gene defect in the chromosome 13q31-q32 region. RESULTS: All affected members of both families had pinpoint pupils which responded normally to light and accommodation. None of these subjects exhibited any other ocular abnormality. The iris of affected members showed stromal thinning and apparent absence of the iris dilator muscle in the first family, but was smooth and lacked all trabecular structure in the second family. The microcoria was present at birth in the first family but developed progressively at a later age in the second family. Haplotype analysis suggested the gene defect is not located in the chromosome 13q31-q32 region in the first family but the evidence was not conclusive in the second family. CONCLUSION: Although both families presented with similar pupil abnormalities inherited as an autosomal dominant trait, they show important phenotypic and genotypic differences suggesting that this is a heterogeneous condition. The possible mechanisms underlying the microcoria are discussed.

Primary musculoskeletal tumors of fibrous origin.

Tumors of fibrous origin include fibrous dysplasia (FD), fibroxanthoma (nonossifying fibroma), cortical desmoid, desmoplastic fibroma, fibrosarcoma, and malignant fibrous histiocytosis (MFH). Benign fibrous lesions (FD, fibroxanthoma, and cortical desmoid) frequently demonstrate pathognomonic radiologic characteristics obviating the need for biopsy. Indeed, biopsy of these lesions can occasionally lead to confusion with more aggressive lesions. Desmoplastic fibroma and the malignant fibrous lesions (fibrosarcoma and MFH) often reveal nonspecific imaging features of a solitary nonmineralized lesion with aggressive characteristics. However, imaging is important as with other neoplasms in delineating the extent of involvement for staging purposes. This article reviews the spectrum of clinical characteristics, pathology, imaging appearances, treatment, and prognosis of lesions of fibrous origin in bone.

Lesions of unknown histogenesis: Langerhans cell histiocytosis and Ewing sarcoma.

Langerhans cell histiocytosis (LCH) and Ewing sarcoma represent lesions of unknown histogenesis. Both lesions typically affect children and adolescents. Imaging features frequently suggest the diagnosis, and both lesions may demonstrate aggressive characteristics. LCH shows a broader spectrum of imaging findings, depending on lesion activity and location, which are reviewed in this article. Ewing sarcoma typically reveals both osseous and soft tissue involvement, although direct continuity of the components is often not apparent. Knowledge of the spectrum of clinical and radiologic features facilitates early diagnosis and can be used to evaluate the effects of therapy.

20-year experience with cemented primary and conversion total hip arthroplasty using so-called second-generation cementing techniques in patients aged 50 years or younger.

We present the 20-year experience of 47 hips in 40 patients aged 50 years or younger with cemented primary total hip arthroplasty using second-generation femoral cementing techniques. Average follow-up duration in the 23 patients living at least 17 years was 18.2 years. Overall, 18 hips (38%) had components revised or removed for any reason, at an average duration of 12.6 years. Every revision or reoperation involved removing the acetabular component. Of these 18 acetabular components, 15 (32%) were revised for aseptic loosening. Eleven additional acetabular components were loose by radiographic criteria at final follow-up, yielding prevalence of aseptic acetabular loosening (55%). Four femoral components (8%) were revised for osteolysis without loosening, and 3 (6%) were revised for aseptic loosening. Femoral osteolysis, with or without component loosening, led to revision in 5 ( 11%) hips compared with 6% for aseptic loosening alone. Osteolysis was the primary problem leading to acetabular and femoral component revision in this series of people < or = 50 years old over the first 20 years after the index operation.

Pupil abnormality in amyloidosis with autonomic neuropathy.

Darkness pupil diameters, light reflexes, and redilatation times have been recorded with infrared TV pupillometry in 12 consecutive patients with systemic amyloidosis associated with sensory motor and autonomic neuropathy. Nine of the patients had AL amyloidosis, two had familial amyloidosis associated with a transthyretin abnormality, and one was untyped. The pupils were abnormal in all 12 patients. On the basis of redilatation lag without pupillotonia, six patients had bilateral Horner's syndrome and in one of them amyloid deposits were found in a sympathetic ganglion and in the attached sympathetic chain obtained at necropsy. Four patients had bilateral tonic pupils with light-near dissociation and two had abnormally small pupils with reduced light reactions which could not be characterised. It seems that in patients with systemic amyloidosis generalised autonomic neuropathy is strongly associated with pupil abnormality as shown by tonic reactions with light-near dissociation, by redilatation lag, or by reduced size in darkness.

From the archives of the AFIP. Imaging of musculoskeletal neurogenic tumors: radiologic-pathologic correlation.

Numerous neurogenic tumors can affect the musculoskeletal system, including traumatic neuroma, Morton neuroma, neural fibrolipoma, nerve sheath ganglion, neurilemoma, neurofibroma, and malignant peripheral nerve sheath tumors (PNSTs). The diagnosis of neurogenic tumors can be suggested from their imaging appearances, including lesion shape and intrinsic imaging characteristics. It is also important to establish lesion location along a typical nerve distribution (eg, plantar digital nerve in Morton neuroma, median nerve in neural fibrolipoma, large nerve trunk in benign and malignant PNSTs). Traumatic and Morton neuromas are commonly related to an amputation stump or are located in the intermetatarsal space, respectively. Neural fibrolipomas show fat interspersed between nerve fascicles and are often associated with macrodactyly. Nerve sheath ganglion has a cystic appearance and commonly occurs about the knee. Radiologic characteristics of neurilemoma, neurofibroma, and malignant PNST at computed tomography (CT), ultrasonography, and magnetic resonance imaging include fusiform shape, identification of entering and exiting nerve, low attenuation at CT, target sign, fascicular sign, split-fat sign, and associated muscle atrophy. Although differentiation of neurilemoma from neurofibroma and of benign from malignant PNST is problematic, recognition of the radiologic appearances of neurogenic tumors often allows prospective diagnosis and improves clinical management of patients.

Bilateral Horner's syndrome: detection and occurrence.

OBJECTIVE: To develop a method for the detection of bilateral Horner's syndrome in patients with bilateral interruption of the cervical sympathetic pathway or widespread autonomic neuropathy. METHODS: Darkness pupil diameters and redilatation times during light reflexes have been recorded with infrared TV pupillometry in 65 healthy subjects, 47 patients with unilateral Horner's syndrome, and 20 patients with bilateral Horner's syndrome. The aetiologies of the last group were diabetic autonomic neuropathy (three cases), amyloidosis (four), pure autonomic failure (PAF) (four), dopamine-beta-hydroxylase deficiency (two), and one case each of hereditary sensory and autonomic neuropathy (HSAN) type III, carcinomatous sympathetic neuropathy, familial dysautonomia, multiple system atrophy, Anderson-Fabry disease, and anterior spinal artery thrombosis at C5,6 and one had had bilateral cervical sympathectomies. RESULTS: Darkness diameters on the affected side were below normal in 12 patients with unilateral Horner's syndrome, the measurement yielding only 26% sensitivity for detection of the condition. By contrast, the time taken to reach three quarter recovery in the light reflex (T3/4) was abnormally prolonged (redilatation lag) in 33 of the same eyes. The measurement yielded 70% sensitivity and 95% specificity for detection of the condition. In 20 cases, diagnosed on clinical grounds as having bilateral Horner's syndrome of various aetiologies, pupil diameters were abnormally small on both sides in five and on one side in three patients. Fourteen of these patients had significant redilatation lag in both eyes, five patients in one eye, and one patient had it in neither eye. Measurement of redilatation lag was therefore a more sensitive diagnostic test than pupil diameter in both unilateral and bilateral Horner's syndrome. CONCLUSIONS: Provided that the pupils are not tonic, bilateral Horner's syndrome can be diagnosed on the basis of redilatation lag. It occurs clinically in some generalised autonomic neuropathies and with interruption of the local sympathetic nerve supplies to the two eyes.

A smoking cessation programme conducted through dental practices in the UK.

OBJECTIVES: To assess the feasibility of using primary care dentists and the dental team providing smoking cessation advice in practice. DESIGN: A prospective study to examine the success of a smoking cessation programme. SETTING: 54 primary care dental practices in the UK. METHOD: Training and educational materials were supplied to members of the dental team and to potential recruits smoking 10 or more cigarettes a day. Recruitment was over 6 months and subjects were followed up for 9 months. In addition to dentists' counselling, nicotine patches were made available, on request, at cost price. Salivary cotinine assay was used for validation of smoking levels at initial counselling and 9 months after recruitment. RESULTS: 54 practices were enrolled but only 22 recruited patients. Records of 154 eligible patients were evaluated. Compliance to attend follow up clinics was poor--only 74 reported at 9 months. Among them 17 (11%) were successful in giving-up tobacco for 9 months as validated by patient histories and salivary cotinine assay. A large variation performance of the dental practices was noted. CONCLUSIONS: Motivated dentists with staff support and access to information on smoking counselling are able to contribute to tobacco control measures in the community. The success of this programme closely parallels those reported in general medical practice settings. In view of the very considerable attrition rates found at all levels of the programme in the present study and the uneven performance of the participating practices the quit rate reported here may not accurately reflect what could be achieved in an individual primary care setting.