Lymphangioleiomyomatosis in patients with tuberous sclerosis: a national centre audit.

BACKGROUND: Lymphangioleiomyomatosis (LAM) is common in tuberous sclerosis complex (TSC) yet under recognised with management mostly based upon evidence obtained from patients with sporadic LAM. We performed a prospective audit of patients with TSC-LAM attending a national referral centre to inform management guidelines. METHODS: The UK LAM Centre was established in 2011 and conducts a prospective audit of pre-defined quality outcomes for all subjects. Audit data are reported on all patients with TSC-LAM and a comparator population of patients with sporadic LAM. RESULTS: Between 2011 and 2022, 73 patients were seen with TSC-LAM. All were women with a mean (SD) age of 39 (12) years. Referral rates were similar over the study period including after the introduction of CT screening. Median age of diagnosis with TSC was 11 years (range 0-70) with one third diagnosed with TSC as adults. Compared with all TSC patients in the 'TOSCA' registry, TSC-LAM patients tended to have been diagnosed with TSC at an older age, had fewer neuro-cognitive manifestations and were more likely to have angiomyolipoma. The most common presentations of TSC-LAM were following workup for angiomyolipoma, pneumothorax or dyspnoea with only one fifth detected after CT screening. Baseline FEV1 and DLCO at first assessment were reduced to 77 and 63% predicted respectively and were similar to patients with sporadic LAM. During follow-up, FEV1 fell by a mean of 81 ml/year and DLCO fell by 0.309 mmol/ml/kPa/year in patients not being treated with an mTOR inhibitor. 55% required treatment with either sirolimus or Everolimus for LAM or angiomyolipoma respectively. For those treated with an mTOR inhibitor, mean FEV1 fell by 3 ml/year and DLCO increased by 0.032 mmol/ml/kPa/year and was similar to sporadic LAM. Risk of death due to LAM or need for lung transplant in patients with TSC-LAM was 0.67%/year. CONCLUSIONS: Despite screening recommendations, LAM is often diagnosed in TSC after symptoms develop which may delay treatment. Complications including pneumothorax and loss of lung function are significant and similar to sporadic LAM. Work is needed to implement the recommended CT screening for LAM and improve respiratory care for TSC-LAM.

Disease monitoring using lung function trajectory in lymphangioleiomyomatosis: assessment in two national cohorts.

STUDY QUESTION: In lymphangioleiomyomatosis, airflow obstruction and impairment of gas transfer progress at variable rates and serial lung function is recommended for disease monitoring. As these measurements are variable, recognising subjects needing treatment can be difficult. We used two prospective national cohorts to study change over time and variation in FEV1 to inform clinical decision making. PATIENTS AND METHODS: Clinical and lung function data for 141 UK and 148 American subjects were studied. Multilevel mixed effects modelling, route mean square analysis of errors and Bland-Altman analysis were used to analyse variability in lung function over time. RESULTS: At baseline assessment, DLCO was reduced to a greater degree than FEV1. In untreated patients, FEV1 and DLCO declined at proportionately similar rates independent of initial lung function. In mechanistic target of rapamycin (mTOR) inhibitor treated patients, FEV1 stabilised but DLCO continued to decline. FEV1/DLCO per cent predicted ratio was 1.37 (0.43) at baseline and increased to 1.41 (0.50) after 42 (24) months (p=0.0002). At least five measurements were required before >70% of individuals had estimates of rate of FEV1 loss within 50 mL/year and DLCO loss within 0.1 mmol/min/kPa/year of the final values. CONCLUSIONS: While FEV1 and DLCO fall proportionately in most, in early disease and during mTOR inhibitor treatment, DLCO should also be monitored as it may fall independent of FEV1. Since at least five observations over many months are required to make confident estimates of FEV1 and DLCO trajectories, new strategies are needed to measure disease activity and target early treatment appropriately.

Pregnancy in lymphangioleiomyomatosis: clinical and lung function outcomes in two national cohorts.

Pregnancy in women with lymphangioleiomyomatosis (LAM) has been associated with increased complications and worsening lung function although objective data to advise patients are not available. We assessed lung function and CT scans before and after pregnancy in 16 women with LAM. During the pregnancy, pneumothorax was frequent and mean forced expiratory volume in 1 s (FEV1) fell from 77%±19% prepregnancy to 64%±25% predicted and DLCO from 66±26 to 57±26 (both p<0.01). After pregnancy, rates of FEV1 decline were high and 10 patients required sirolimus. Women with LAM, especially with moderate or advanced disease should be counselled regarding adverse events and loss of lung function during the pregnancy.

Cross-sectional study of reversible airway obstruction in LAM: better evidence is needed for bronchodilator and inhaled steroid use.

Lymphangioleiomyomatosis can be associated with reversible airflow obstruction and although no guidelines around reversibility testing or inhaled therapy exist, many patients receive bronchodilators and inhaled corticosteroids. To better identify those who may benefit, we examined bronchodilator reversibility and inhaled therapy in a national cohort of 213 subjects. 20% of those tested had airway reversibility by standard criteria. 55% of patients used 13 different combinations of bronchodilators and inhaled corticosteroids. Increasing inhaler classes were associated with reversibility and more rapid FEV1 decline. Reversibility testing should be performed in all patients and inhaled therapy should be formally studied.

2014 Guideline for Management of Wounds in Patients With Lower-Extremity Arterial Disease (LEAD): An Executive Summary.

The purpose of this article is to provide a summary of the recommendations from the 2014 Guideline for Management of Wounds in Patients With Lower-Extremity Arterial Disease (LEAD), published by the Wound, Ostomy and Continence Nurses Society (WOCN). This article provides an overview of the process used to update and develop the guideline, and specific recommendations from the guideline for assessment, referral for further evaluation, interventions (ie, debridement, dressings, infection, antibiotics, nutrition, pain management, compression issues, medications, surgical options, and adjunctive therapies), and patient education and risk-reduction strategies. The LEAD guideline is a resource for physicians, nurses, therapists, and other healthcare professionals who work with adults who have/or are at risk for wounds due to LEAD. The full text of the published guideline, which includes the available evidence supporting the recommendations and a complete reference list, is available from the WOCN Society, 1120 Rt. 73, Suite 200, Mount Laurel, NJ, 08054; Web site: www.wocn.org. Refer to the Supplemental Digital Content (Supplement Digital Content 1, http://links.lww.com/JWOCN/A31) associated with this article for the complete reference list for the guideline. The guideline has been accepted for publication by the National Guideline Clearinghouse (www.guideline.gov/).

Chronic venous disease and venous leg ulcers: An evidence-based update.

Chronic venous disease (CVD) is a complex chronic vascular condition with multifaceted primary and secondary etiologies leading to structural and functional changes in veins and valves and blood flow of the lower legs. As a consequence, a spectrum of clinical manifestations arise, ranging from symptoms of mild leg heaviness and achiness to debilitating pain, and signs of skin changes, such as eczema and hemosiderosis, to nonhealing, heavily draining venous leg ulcers (VLUs). Triggers such as trauma to the skin are responsible for a large majority of VLU recurrences. Diagnostic testing for venous reflux includes ultrasound imaging; unfortunately, there are no diagnostic tests to predict VLUs. The hallmark of treatment of both CVD and VLUs is compression. Leg elevation, exercise, and wound management with dressings and advanced healing technologies that provide an environment conducive to healing should focus on reducing pain, necrotic debris, drainage, and odor, as well as preventing infection. VLUs that become chronic without evidence of healing over a 4-week period respond best to multidisciplinary wound experts within a framework of patient-centered care. Nurses are in key positions to provide early recognition of the signs and symptoms as well as initiate prompt diagnostic and promote early treatment to offset the progression of the disease and improve quality of life.

Guideline for the management of wounds in patients with lower-extremity venous disease: an executive summary.

This article provides an executive summary of the lower extremity venous disease (LEVD) evidence-based guideline produced by the WOCN Wound Guidelines Task Force. The target audience for this guideline is health care professionals who specialize in, direct, or provide wound care for patients at risk for or with lower-extremity venous disease. The full guideline opens with an overview of definitions of LEVD, its prevalence, clinical relevance, etiology, related physiology and pathophysiology, and overall management goals for patients at risk for developing venous leg ulcers. A detailed assessment section describes how to conduct a full clinical history and physical examination. Two approaches to interventions are provided: one addresses prevention strategies to reduce the risk of developing LEVD with ulcers. Methods to prevent ulcer recurrence are summarized including compression therapy, adjunctive therapies, medications, and patient education. A second approach presents treatment interventions including wound cleansing, debridement, infection control, antibiotic use, along with management of the periwound skin, nutrition, pain, and edema. This section also discusses limb elevation, surgical options, adjunctive therapies, patient education, and health care provider follow-up. A comprehensive reference list, glossary of terms, and appendices on cellulitis and venous eczema, types of edema, and compression therapy are available at the end of the guideline. This article provides an executive summary of the essential features of the guideline.

Catastrophic injuries in pole vaulters: a prospective 9-year follow-up study.

BACKGROUND: A prior review of catastrophic pole vaulting injuries from 1982 through 1998 revealed an average of 2.0 injuries per year, with 69% (1.38 per year) of the injuries secondary to athletes landing off the sides or back of the landing pad and 25% (0.5 per year) from athletes landing in the vault box. In 2003, several rule changes for the sport of pole vaulting were mandated, including enlarging the minimum dimensions of the landing pad. HYPOTHESIS/PURPOSE: Our goals were to (1) identify the post-2003 rule change incidence and profile of catastrophic pole vaulting injuries through 2011 and compare them, where possible, with the prior incidence and profile and (2) determine, via a questionnaire, the frequency with which pole vaulters land in the vault box. We hypothesized that the new, larger landing pads would reduce the number of catastrophic injuries. STUDY DESIGN: Descriptive epidemiology study. METHODS: We prospectively reviewed all catastrophic pole vaulting injuries (ie, brain hemorrhage; skull, spine, or pelvic fracture; substantial pulmonary or intra-abdominal injury) in the United States from 2003 through 2011, surveyed 3335 pole vaulters to determine the frequency of landing in the vault box, and compared results with those in the literature. RESULTS: From 2003 to 2011, 19 catastrophic injuries occurred (average of 2.1 per year), with the majority (n = 14, 74%, 1.55 per year) landing in or around the vault box. Four (21%, 0.44 per year) injuries occurred when an athlete landed off the sides or back of the landing pad and 1 (5%) when the pole broke. There were 11 (58%) major head injuries (1 fatality), 4 (21%) spine fractures (1 with paraplegia), 2 (11%) pelvic fractures (both with intra-abdominal injuries), 1 (5%) brain stem injury (fatal), and 1 (5%) thoracic injury (rib fractures and pneumothorax). The annual fatality rate fell from 1.0 in the prior study to 0.22 in the current study. According to the pole vaulters survey, during their careers, 77.12% (n = 2572) landed in the vault box 1 to 3 times, 15.92% (n = 531) never landed in the vault box, 6.12% (n = 204) landed in the vault box 4 to 6 times, and 0.84% (n = 28) landed in the vault box 7 or more times. CONCLUSION: The 2003 rule changes have markedly reduced the number of catastrophic injuries, especially fatalities, from pole vaulters missing the back or sides of the landing pads; however, the average annual rate of catastrophic injuries from pole vaulters landing in the vault box has more than tripled over the past decade and remains a major problem.

Thrombocytopenias due to gray platelet syndrome or THC2 mutations.

Over the last two decades the genetic causes of several Mendelian platelet disorders have been elucidated, while the genetics of many other thrombocytopenic conditions are still unresolved. Among those are the gray platelet syndrome (GPS) and the thrombocytopenia linked to the THC2 locus on human chromosome 10p11-12. GPS is an α-granule defect associated with the development of myelofibrosis and mild to moderate thrombocytopenia. Most forms of GPS are autosomal recessive, and recently, the recessive form of the disease was mapped to chromosome 3p21. THC2-linked thrombocytopenia is an autosomal dominant disorder in which affected family members have a mild reduction in platelet counts and occasional bleeding. Platelets in THC2-linked thrombocytopenia appear to be normal in size and function although bone marrow morphology reveals a lack of mature, polyploid megakaryocytes. To date, mutations in three different genes within the THC2 locus have been associated with congenital thrombocytopenia, including a mutation in MASTL. In this article, we summarize the recent discoveries in these two forms of thrombocytopenia, including the functional data that support a role for MASTL kinase in thrombopoiesis.

What's new in lower-extremity arterial disease? WOCN's 2008 clinical practice guideline.

Lower-extremity arterial disease (LEAD) affects 8 to 10 million people in the United States, resulting in pain, tissue loss, infection, limb loss, and an impaired quality of life. LEAD is underdiagnosed, undertreated, and often unrecognized. The purpose of this article is to provide a summary of the recommendations from the 2008 evidence-based, clinical practice guideline, Guideline for the Management of Patients With Lower-Extremity Arterial Disease, recently released from the Wound, Ostomy and Continence Nurses Society. This article presents an overview of the process used to develop the guideline, a discussion of risks for LEAD, and specific recommendations for assessment, interventions, patient education, and risk-reduction strategies.

Expression of the GPI-anchored receptor Prv-1 enhances thrombopoietin and IL-3-induced proliferation in hematopoietic cell lines.

Prv-1 is a hematopoietic cell surface receptor that has been shown to be overexpressed in patients diagnosed with polycythemia vera (PV) and essential thrombocythemia (ET), yet its cellular function remains unclear. In this study, we assessed the role of Prv-1 in thrombopoietin (Tpo)/Mpl signaling with the goal of identifying molecular mechanisms which augment Tpo-induced proliferation. By engineering the cytokine-dependent hematopoietic cell line BaF3 to express both Prv-1 and wild-type or mutant forms of Mpl, we were able to follow the time course of Tpo-dependent proliferation. We report that the overexpression of Prv-1 increased Tpo as well as IL-3-induced proliferation of BaF3/Mpl and BaF3 cells. Cells co-expressing Prv-1 and an Mpl receptor containing a Box 1 motif mutation, which fails to activate Jak2, was completely deficient in Tpo-dependent proliferation. In addition, BaF3 and BaF3/Prv-1 cells stimulated with IL-3 in the presence of the Jak2 inhibitor, AG490, abrogated the proliferative response, indicating that Prv-1 requires a functional Jak2 for its signaling activities. Western blot analysis showed an increase in Tpo and IL-3-induced Stat3 and Stat5 tyrosine phosphorylation in BaF3/Mpl and BaF3 cells expressing Prv-1. These results indicate a novel function for Prv-1 as a signaling molecule in cytokine signaling cascades and may lead to a greater understanding of the mechanism of overexpression of Prv-1 in myeloproliferative disorders.

Supporting employment for adults with acquired brain injury: a conceptual model.

Employment, or return-to-work, is a common goal for adults who have experienced brain injury. Unfortunately, many individuals suffer significant psychosocial, cognitive, and physical deficits as a result of the injury that negatively affect their ability to seek or maintain employment. Research points to the importance of addressing these deficits using a supportive vocational rehabilitation team approach that focuses on assessing a wide range of cognitive, physical, and functional variables. The purpose of this article is to describe the Brain Injury Assessment Model (BIAM) for use as a vocational assessment tool for clients diagnosed with acquired brain injury and who are seeking employment or are returning to work.

Cognitive-behavioral treatment of food neophobia in adults.

Food neophobia is an eating disturbance defined as the fear of trying new foods. In its extreme, the disorder can lead to malnutrition, limited social functioning, and psychological difficulties. Successful treatment of food neophobia in children has been reported, but if those children are not provided with treatment, it stands to reason that the disorder may follow them into adulthood. To date, adult cases have not been described in the literature and the prevalence in adults is unknown. Our paper will review the methods used to treat children with the disorder then delineate how the procedures were modified for an adult population, giving two case examples.

Cognitive-behavioral treatment of food neophobia in adults.

Food neophobia is an eating disturbance defined as the fear of trying new foods. In its extreme, the disorder can lead to malnutrition, limited social functioning, and psycholo gical difficulties. Successful treatment of food neophobia in children has been reported, but if those children are not provided with treatment, it stands to reason that the disorder may follow them into adulthood. To date, adult cases have not been described in the literature and the prevalence in adults is unknown. Our paper will review the methods used to treat children with the disorder, then delineate how the procedures were modified for an adult population, giving two case examples.