Lymphangioleiomyomatosis: What do we know and what are we looking for?

Lymphangioleiomyomatosis (LAM) is a rare disease characterised by proliferation of abnormal smooth muscle-like cells (LAM cells) leading to progressive cystic destruction of the lung, lymphatic abnormalities and abdominal tumours. It affects predominantly females and can occur sporadically or in patients with tuberous sclerosis complex. This review describes the recent progress in our understanding of the molecular pathogenesis of the disease and LAM cell biology. It also summarises current therapeutic approaches and the most promising areas of research for future therapeutic strategies

Thoracic involvement in generalised lymphatic anomaly (or lymphangiomatosis)

Generalised lymphatic anomaly (GLA), also known as lymphangiomatosis, is a rare disease caused by congenital abnormalities of lymphatic development. It usually presents in childhood but can also be diagnosed in adults. GLA encompasses a wide spectrum of clinical manifestations ranging from singleorgan involvement to generalised disease. Given the rarity of the disease, most of the information regarding it comes from case reports. To date, no clinical trials concerning treatment are available. This review focuses on thoracic GLA and summarises possible diagnostic and therapeutic approaches

Severe idiopathic pulmonary fibrosis: What can be done?

Idiopathic pulmonary fibrosis (IPF) remains a challenging disease to manage. Two drugs are now available that can slow disease progression in patients with mild-to-moderate IPF. This means that early diagnosis is mandatory, because there are no proven effective therapies for severe IPF. This lack of proven therapies may be at least partially due to the fact that severe IPF patients are usually not enrolled in randomised, prospective, multicentre, international trials. Clinical observation experiences and preliminary results of long-term, open-label extensions of clinical trials suggest that both pirfenidone and nintedanib may also slow or decrease progression in patients with severe IPF. However, data are sparse and obtained from a relatively small number of patients. Lung transplantation should be taken into account early and discussed with patients, when indicated. Rehabilitative strategies are important and effective supportive therapies. The needs of patients with severe IPF are similar to those of patients with an advanced neoplastic disease. Palliative care and psychological support play an important role in the relief of symptoms of anxiety and depression. Accordingly, these therapeutic approaches should start early in IPF patients

New insights in lymphangioleiomyomatosis and pulmonary langerhans cell histiocytosis

Lymphangioleiomyomatosis (LAM) and pulmonary Langerhans cell histiocytosis (PLCH) are rare diseases that lead to progressive cystic destruction of the lungs. Despite their distinctive characteristics, these diseases share several features. Patients affected by LAM or PLCH have similar radiological cystic patterns, a similar age of onset, and the possibility of extrapulmonary involvement. In this review, the recent advances in the understanding of the molecular pathogenesis, as well as the current and most promising biomarkers and therapeutic approaches, are described

The Joint Observation in Neonatology and Neurodevelopmental Outcome of Preterm Infants at Six Months Corrected Age: Secondary Outcome Data from a Randomised Controlled Trial.

This study aimed to evaluate the impact of a standardised joint observation (JOIN) performed in the neonatal intensive care unit (NICU) on the neurodevelopment of preterm infants at six months corrected age (CA) compared with a preterm control group. In this monocentric interventional randomised controlled trial, we allocated 76 mothers and their preterm neonates to either JOIN, an early one-session intervention, or standard care during the NICU hospitalisation. The neurodevelopment of the preterm infants was assessed by standardised developmental tests at six months CA and compared between the intervention and the control groups. This randomised controlled trial was registered on clinicaltrials.gov (NCT02736136) in April 2016. Sixty-five infants underwent neurodevelopmental assessment at six months CA. There were no significant differences between the two groups in neurodevelopmental outcome measures. The JOIN intervention was not associated with significant improvement in neurodevelopment at six months CA in preterm infants

Sirolimus Therapy for Patients With Lymphangioleiomyomatosis Leads to Loss of Chylous Ascites and Circulating LAM Cells

A young woman received a diagnosis of abdominal, sporadic lymphangioleiomyomatosis (LAM) and multiple abdominal lymphangioleiomyomas and was referred for recurrent chylous ascites responding only to a fat-free diet. On admission, pulmonary function test (PFT) results showed a moderate reduction in the transfer factor for carbon monoxide with normal exercise performance. The serum vascular endothelial growth factor D (VEGF-D) level was 2,209 pg/mL. DNA sequences, amplified at loci kg8, D16S3395, D16S3024, D16S521, and D16S291 on chromosome 16p13.3, showed a loss of heterozygosity (LOH) only for kg8. Fat-free total parenteral nutrition in association with sirolimus (2 mg po daily) was initiated. Serum sirolimus levels were maintained at concentrations between 5 and 15 ng/mL. After 1 month, reintroduction of a low-fat oral feeding was achieved without recurrence of ascites. PFT results were stable. Interestingly, clinical improvement was associated with a reduction in the VEGF-D serum level (1,558 pg/mL). LOH at the kg8 biomarker in blood LAM cells was no longer detected

Stimulation of the tibial nerve: a protocol for a multicentred randomised controlled trial for urinary problems associated with Parkinson’s disease—STARTUP

Introduction Parkinson’s disease is the second most common chronic neurodegenerative condition with bladder dysfunction affecting up to 71%. Symptoms affect quality of life and include urgency, frequency, hesitancy, nocturia and incontinence. Addressing urinary dysfunction is one of the top 10 priority research areas identified by the James Lind Alliance and Parkinson’s UK. Objectives Conduct a randomised controlled trial (RCT) targeting people with Parkinson’s disease (PwP) who have self-reported problematic lower urinary tract symptoms, investigating the effectiveness of transcutaneous tibial nerve stimulation (TTNS) compared with sham TTNS. Implement a standardised training approach and package for the correct application of TTNS. Conduct a cost-effectiveness analysis of TTNS compared with sham TTNS. Methods and analysis An RCT of 6 weeks with twice weekly TTNS or sham TTNS. Participants will be recruited in 12 National Health Service neurology/movement disorder services, using a web-based randomisation system, and will be shown how to apply TTNS or sham TTNS. Participants will receive a weekly telephone call from the researchers during the intervention period. The trial has two coprimary outcome measures: International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form and the International Prostate Symptom Score. Secondary outcomes include a 3-day bladder diary, quality of life, acceptability and fidelity and health economic evaluation. Outcomes will be measured at 0, 6 and 12 weeks. A sample size of 208 randomised in equal numbers to the two arms will provide 90% power to detect a clinically important difference of 2.52 points on the Internatioanl Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF) and of 3 points in the International Prostate Symptom Score total score at 12 weeks at 5% significance level, based on an SD of 4.7 in each arm and 20% attrition at 6 weeks. Analysis will be by intention to treat and pre defined in a statistical analysis plan Ethics and dissemination East of Scotland Research Ethics Service (EoSRES), 18/ES00042, obtained on 10 May 2018. The trial will allow us to determine effectiveness, safety, cost and acceptability of TTNS for bladder dysfunction in PWP. Results will be published in open access journals; lay reports will be posted to all participants and presented at conferences. Trial registration number ISRCTN12437878; Pre-results

Rotating charged Black Holes in Einstein-Born-Infeld theories and their ADM mass

In this work, the solution of the Einstein equations for a slowly rotating black hole with Born-Infeld charge is obtained. Geometrical properties and horizons of this solution are analyzed. The conditions when the ADM mass (as in the nonlinear static cases) and the ADM angular momentum of the system have been modified by the non linear electromagnetic field of the black hole, are considered.Comment: Final version and figures in journal. References and comments adde

Percolation on the average and spontaneous magnetization for q-states Potts model on graph

We prove that the q-states Potts model on graph is spontaneously magnetized at finite temperature if and only if the graph presents percolation on the average. Percolation on the average is a combinatorial problem defined by averaging over all the sites of the graph the probability of belonging to a cluster of a given size. In the paper we obtain an inequality between this average probability and the average magnetization, which is a typical extensive function describing the thermodynamic behaviour of the model

Weak-Lensing by Large-Scale Structure and the Polarization Properties of Distant Radio-Sources

We estimate the effects of weak lensing by large-scale density inhomogeneities and long-wavelength gravitational waves upon the polarization properties of electromagnetic radiation as it propagates from cosmologically distant sources. Scalar (density) fluctuations do not rotate neither the plane of polarization of the electromagnetic radiation nor the source image. They produce, however, an appreciable shear, which distorts the image shape, leading to an apparent rotation of the image orientation relative to its plane of polarization. In sources with large ellipticity the apparent rotation is rather small, of the order (in radians) of the dimensionless shear. The effect is larger at smaller source eccentricity. A shear of 1% can induce apparent rotations of around 5 degrees in radio sources with the smallest eccentricity among those with a significant degree of integrated linear polarization. We discuss the possibility that weak lensing by shear with rms value around or below 5% may be the cause for the dispersion in the direction of integrated linear polarization of cosmologically distant radio sources away from the perpendicular to their major axis, as expected from models for their magnetic fields. A rms shear larger than 5% would be incompatible with the observed correlation between polarization properties and source orientation in distant radio galaxies and quasars. Gravity waves do rotate both the plane of polarization as well as the source image. Their weak lensing effects, however, are negligible.Comment: 23 pages, 2 eps figures, Aastex 4.0 macros. Final version, as accepted by ApJ. Additional references and some changes in the introduction and conclusion