Association of Mycoplasma genitalium with nongonococcal urethritis in heterosexual men

Chlamydia trachomatis and Neisseria gonorrhoeae are universally acknowledged as urethral pathogens, yet the etiology in the majority of cases of urethritis is unclear. Our case-control study assessed the association of Mycoplasma genitalium, Ureaplasma urealyticum, and other potential pathogens with acute nongonococcal urethritis (NGU) in heterosexual men presenting to an urban sexually transmitted diseases clinic. M. genitalium was detected in 27 (22%) of 121 NGU case patients and in 5 (4%) of 117 control subjects (P<.01). Although C. trachomatis was detected in 36 (30%) of 121 NGU case patients and in 4 (3%) of 117 control subjects (P<.01), only 3 men with NGU were infected with both C. trachomatis and M. genitalium. U. urealyticum was not associated with NGU. By multivariate analyses, controlling for age, race, history of prior urethritis, and chlamydial infection, M. genitalium was associated with a 6.5-fold increased risk of urethritis (95% confidence interval, 2.1-19.5), which supports a role of this organism in the etiology of NGU.     

The use of an implantable loop recorder in the investigation of unexplained syncope in older people

INTRODUCTION: Reveal is a patient activated implantable loop recorder device with an 18 month battery life now available to assist in the diagnosis of suspected syncope or arrhythmias. We present our experience using this device in older subjects referred to a dedicated falls and syncope clinic in whom usual clinical assessment had not satisfactorily identified an attributable diagnosis but where we still suspected a cardiovascular cause for syncope or falls. METHODS AND RESULTS: during the past 3 years 15 subjects (mean age 73 years, range 61-89 years) had Reveal implanted for symptoms of syncope alone (n=6; 40%) and unexplained falls (n=3; 20%) or symptoms of syncope and unexplained falls (n=6; 40%). Symptom duration was long (mean 48 months; range 4-200 months). Subjects had experienced significant morbidity, 6 subjects (40%) required A&E attendance or hospital admission and 4 (27%) experienced a fracture. Despite extensive and repeated investigations, which included 12-lead ECG, echocardiogram, 24-h ambulatory heart rate monitor, 24-h ambulatory blood pressure monitor, orthostatic blood pressure measurement, supine and erect carotid sinus massage, electroencephalogram, and passive and GTN head up tilt testing, the attributable diagnosis remained unexplained. Of the 15 subjects, 7 have activated the device at 4 (range 0-14) months after implantation. Bradycardia was identified in 3 and ventricular tachycardia in 1 subject. Two subjects did not activate the device during the 18 months it was in-situ. Four people had problems with device activation. This is comparable to rates noted using Reveal in younger subjects. CONCLUSION: Reveal offers additional diagnostic yield in complex elderly subjects with suspected cardiovascular causes of syncope or unexplained falls which have not been previously satisfactorily diagnosed despite extensive investigations.     

Moving beyond HLA: A review of nHLA antibodies in organ transplantation

Given the finite graft life expectancy of HLA identical organ transplants and the recognition of humoral graft injury in the absence of donor directed anti-HLA antibodies, the clinical impact of antibodies against non-HLA (nHLA) antigens in transplant injury is being increasingly recognized. The recognition of the impact of nHLA antigen discrepancies between donor and recipient on transplant outcomes is timely given the advances in rapid and lower cost sequencing methods that can soon provide complete maps of all recipient and donor HLA and nHLA mismatch data. In this review, we present a summary of recent reports evaluating the role of nHLA antibodies and their relevance to the field of organ transplantation.     

Tumor location and nature of lymphatic vessels are key determinants of cancer metastasis

Tumor metastasis to lymph nodes is a key indicator of patient survival, and is enhanced by the neo-lymphatics induced by tumor-secreted VEGF-C or VEGF-D, acting via VEGFR-3 signalling. These targets constitute important avenues for anti-metastatic treatment. Despite this new understanding, clinical observations linking metastasis with tumor depth or location suggest that lymphangiogenic growth factors are not the sole determinants of metastasis. Here we explored the influence of tumor proximity to lymphatics capable of responding to growth factors on nodal metastasis in a murine VEGF-D over-expression tumor model. We found that primary tumor location profoundly influenced VEGF-D-mediated lymph node metastasis: 89 % of tumors associated with the flank skin metastasised, in contrast with only 19 % of tumors located more deeply on the body wall (p < 0.01). Lymphatics in metastatic tumors arose from small lymphatics, and displayed distinct molecular and morphological profiles compared with those found in normal lymphatics. Smaller lymphatic subtypes were more abundant in skin (2.5-fold, p < 0.01) than in body wall, providing a richer source of lymphatics for VEGF-D⁺ skin tumors, a phenomenon also confirmed in human samples. This study shows that the proximity of a VEGF-D⁺ primary tumor to small lymphatics is an important determinant of metastasis. These observations may explain why tumor location relative to the lymphatic network is prognostically important for some human cancers.     

Clinical Supervision in Effectiveness and Implementation Research

The role of clinical supervision in the larger‐scale implementation of effective mental health treatments has begun to attract attention in effectiveness research and implementation science. Clinical supervision approaches demonstrated to support the implementation of effective treatments could provide a fruitful basis for adaptation to the contours and implementation of other interventions. The adaptation of the Multisystemic Therapy supervision model to support the implementation of an innovative, experimental mental health service model called Links to Learning is described. An observational study provides the platform for consideration of the extent to which the Links supervision model was implemented as intended and of challenges to Links implementation illuminated by the supervision process. Implications are considered for research on supervision as a tool to effect the implementation and outcomes of effective treatment and service models in community practice contexts.     

Repeatability and reproducibility of apparent diffusion coefficient and fat fraction measurement of focal myeloma lesions on whole body magnetic resonance imaging

Objective:To assess intra- and inter-reader variability of apparent diffusion coefficient (ADC) and fat fraction (FF) measurement in focal myeloma bone lesions and the influence of lesion size.Methods:22 myeloma patients with focal active disease on whole body MRI were included. Two readers outlined a small (5–10 mm) and large lesion (>10 mm) in each subject on derived ADC and FF maps; one reader performed this twice. Intra- and inter-reader agreement for small and large lesion groups were calculated for derived statistics from each map using within-subject standard deviation, coefficient of variation, interclass correlation coefficient measures, and visualized with Bland–Altman plots.Results:For mean ADC, intra- and inter-reader repeatability demonstrated equivalently low coefficient of variation (3.0–3.6%) and excellent interclass correlation coefficient (0.975–0.982) for both small and large lesions. For mean FF, intra- and inter-reader repeatability was significantly poorer for small lesions compared to large lesions (intra-reader within-subject standard variation estimate is 2.7 times higher for small lesions than large lesions (p = 0.0071), and for inter-reader variations is 3.8 times higher (p = 0.0070)).Conclusion:There is excellent intra- and inter-reader agreement for mean ADC estimates, even for lesions as small as 5 mm. For FF measurements, there is a significant increase in coefficient of variation for smaller lesions, suggesting lesions >10 mm should be selected for lesion FF measurement.Advances in knowledge:ADC measurements of focal myeloma have excellent intra- and inter-reader agreement. FF measurements are more susceptible to lesion size as intra- and inter-reader agreement is significantly impaired in lesions less than 10 mm.