Physical therapy in patients with systemic sclerosis: physical therapists' perspectives on current delivery and educational needs.

OBJECTIVE: To assess the perspectives of physical therapists treating patients with systemic sclerosis (SSc) on their current practice and educational needs. METHOD: In July 2019, 405 SSc patients attending a multidisciplinary SSc programme received a survey on physical therapy. Patients who indicated having received physical therapy in the past 2 years were asked to invite their treating physical therapist to complete a questionnaire including sociodemographic characteristics, referral process, content of treatment, perceived knowledge and skills, and educational needs (mostly yes/no answers). RESULTS: Forty-eight of 80 possibly eligible physical therapists treating SSc patients returned the questionnaire [median age 44 years (interquartile range 35-58); 52% female; median number of SSc patients currently treated: 1 (range 1-4)]. Eighty-one per cent (n = 39) of physical therapists had received a referral, with 69% (n = 27/39) judging its content as insufficient. The most often provided types of exercises were range of motion (96%), muscle-strengthening (85%), and aerobic (71%) exercises, followed by hand (42%) and mouth (10%) exercises. Concerning manual treatment, 65% performed either massage or passive mobilization. Regarding competences, 65% indicated feeling capable of treating SSc patients. Nevertheless, 85% expressed the need for an information website on physical therapy in SSc, and 77% for postgraduate education on SSc. CONCLUSION: Primary care physical therapists treating patients with SSc used a wide range of treatment modalities. Although most stated that they treated very few patients, the majority felt capable of treating SSc patients. Nevertheless, the large majority expressed a need for additional information and educational activities concerning SSc.

Autologous stem-cell transplantation in systemic sclerosis-associated interstitial lung disease: early action in selected patients rather than escalation therapy for all.

Systemic sclerosis (SSc) is a rare rheumatic disease characterised by inflammation, vasculopathy and fibrosis of skin and internal organs. A common complication and a leading cause of death in SSc is interstitial lung disease (ILD). The current armamentarium of treatments in SSc-ILD mainly includes immunosuppressive therapies and has recently been expanded with anti-fibrotic agent nintedanib. Autologous stem cell transplantation (SCT) is increasingly used in progressive diffuse cutaneous SSc. This intensive treatment has been studied in three randomised trials and demonstrated to improve survival and quality of life. In the subsets of patients with SSc-ILD, SCT resulted in stabilisation and modest improvement of lung volumes and disease extent on high resolution computed tomography, but less impact was seen on diffusion capacity. Comparison of SCT outcomes with results from SSc-ILD trials is difficult though, as lung involvement per se was not an inclusion criterion in all SCT trials. Also, baseline characteristics differed between studies. The risk of severe treatment-related complications from SCT is still considerable and patients with extensive lung disease are particularly at risk of complications during transplantation. Therefore SCT should only be provided by experienced multidisciplinary teams in carefully selected patients. Future research needs to include comprehensive pulmonary evaluation and establish whether SCT early in the disease might prevent irreversible pulmonary damage and reduce treatment-related complications. Also, more insight in mechanisms of action of SCT in the lung and predictors for response will improve the use of this treatment in SSc-ILD. In this review the role of SCT in the treatment of SSc-ILD is summarised.

Re-evaluating inclusion criteria for autologous hematopoietic stem cell transplantation in advanced systemic sclerosis: Three successful cases and review of the literature.

Systemic sclerosis is a chronic autoimmune disease with a poor prognosis, particularly when a patient has rapidly progressive skin or pulmonary involvement. Autologous hematopoietic stem cell transplant is an emerging treatment for this condition, that has been demonstrated to be more effective than immunosuppressants. Careful selection of patients has reduced the transplant-related mortality and maximized the likelihood of benefit. In this report, we present three cases of successful autologous hematopoietic stem cell transplant in patients who would not have met inclusion criteria for entrance into the completed hematopoietic stem cell transplant. After >18 months of follow-up, three patients had clinically significant benefit in terms of skin tightening and pulmonary function tests. Future studies of hematopoietic stem cell transplant in systemic sclerosis may aim to carefully liberalize inclusion criteria to include patients who may not have otherwise been treated while still maintaining an acceptable safety profile.

Long-Term Clinical Outcomes of Intercalary Allograft Reconstruction for Lower-Extremity Bone Tumors.

BACKGROUND: Improved survival rates for patients with primary bone tumors of the extremities have increased the demand for reliable and durable reconstruction techniques. Some authors have stated that, after successful ingrowth, allografts are a durable long-term solution. This hypothesis is largely based on small studies with short-to-midterm follow-up. In order to determine the durability of intercalary allograft reconstructions in the lower extremities, we evaluated the long-term clinical outcomes at a minimum of 10 years. METHODS: All patients who received an intercalary allograft reconstruction in a lower extremity between 1980 and 2006 were included in this retrospective multicenter cohort study. One hundred and thirty-one patients with a median age of 19 years were included. Eighty-nine (68%) had a femoral reconstruction, and 42 (32%) had a tibial reconstruction. The most prevalent diagnoses were osteosarcoma (55%), Ewing sarcoma (17%), and chondrosarcoma (12%). The median follow-up was 14 years. A competing risk model was employed to estimate the cumulative incidences of mechanical failure and infection. Patient mortality or progression of the disease was used as a competing event. RESULTS: Nonunion occurred in 21 reconstructions (16%), after a median of 16 months, and was associated with intramedullary nail-only fixation (p < 0.01) and fixation with nonbridging plate(s) (p = 0.03). Allograft fracture occurred in 25 reconstructions (19%) after a median of 42 months (range, 4 days to 21.9 years). Thirteen (52%) of the allograft fractures occurred within 5 years; 8 (32%), between 5 and 10 years; and 4 (16%), at >10 years. With failure for mechanical reasons as the end point, the cumulative incidences of reconstruction failure at 5, 10, and 15 years were 9%, 14%, and 21%, respectively. CONCLUSIONS: Intercalary allograft reconstruction is an acceptable reconstructive option, mainly because of the absence of superior alternatives with a known track record. However, a considerable and continuing risk of mechanical complications should be taken into account. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

The role of innate immune cells in systemic sclerosis in the context of autologous hematopoietic stem cell transplantation.

Systemic sclerosis (SSc) is a complex, heterogeneous autoimmune connective tissue disease. Autologous hematopoietic stem-cell transplantation (AHSCT) has emerged as a valuable treatment option for rapidly progressive diffuse cutaneous SSc (dcSSc) patients, and thus far is the only treatment that has been shown to have a long-term clinical benefit. AHSCT is thought to reintroduce immune homeostasis through elimination of pathogenic self-reactive immune cells and reconstitution of a new, tolerant immune system. However, the mechanism of action underlying this reset to tolerance remains largely unknown. In this study we review the immune mechanisms underlying AHSCT for SSc, with a focus on the role of the innate immune cells, including monocytes and natural killer (NK) cells, in restoring immune balance after AHSCT.

Diagnosing and treating antiphospholipid syndrome: a consensus paper.

INTRODUCTION: The antiphospholipid syndrome (APS) is defined by the occurrence of venous and/or arterial thrombosis and/or pregnancy-related morbidity, combined with the presence of antiphospholipid antibodies (aPL) and/or a lupus anticoagulant (LAC). Large, controlled, intervention trials in APS are limited. This paper aims to provide clinicians with an expert consensus on the management of APS. METHODS: Relevant papers were identified by literature search. Statements on diagnostics and treatment were extracted. During two consensus meetings, statements were discussed, followed by a Delphi procedure. Subsequently, a final paper was written. RESULTS: Diagnosis of APS includes the combination of thrombotic events and presence of aPL. Risk stratification on an individual base remains challenging. 'Triple positive' patients have highest risk of recurrent thrombosis. aPL titres > 99th percentile should be considered positive. No gold standard exists for aPL testing; guidance on assay characteristics as formulated by the International Society on Thrombosis and Haemostasis should be followed. Treatment with vitamin K-antagonists (VKA) with INR 2.0-3.0 is first-line treatment for a first or recurrent APS-related venous thrombotic event. Patients with first arterial thrombosis should be treated with clopidogrel or VKA with target INR 2.0-3.0. Treatment with direct oral anticoagulants is not recommended. Patients with catastrophic APS, recurrent thrombotic events or recurrent pregnancy morbidity should be referred to an expert centre. CONCLUSION: This consensus paper fills the gap between evidence-based medicine and daily clinical practice for the care of APS patients.

A case of regional migratory osteoporosis.

We present the case of a middle-aged man with three episodes of regional migratory osteoporosis of the lower extremities occurring over a period of 8 years. Symptoms included a sudden onset of unilateral bone and joint pain. After initiation of pamidronate treatment, symptoms improved significantly. Regional migratory osteoporosis is a rare, but probably underdiagnosed condition with an unclear etiology. This case illustrates the importance of recognition of the disease in order to inform the patient, start treatment, and prevent unnecessary invasive procedures. Although in literature, not much is reported about treatment strategies, our patient was successfully treated with pamidronate after failure of oral bisphosphonates.

Incidentally detected diffuse signal alterations of bone marrow on MRI: is bone marrow biopsy indicated?

BACKGROUND: Advanced imaging techniques as magnetic resonance imaging (MRI) are increasingly performed in the diagnostic workup of patients. Incidentally, diffuse signal alterations of the bone marrow are detected because MRI visualises various components of the bone marrow. The clinical significance of these signal alterations is unknown. OBJECTIVE: The main goal of this study was to determine the diagnostic value of a bone marrow biopsy in patients with incidentally found diffuse signal alterations of the bone marrow. METHODS: We retrospectively examined all bone marrow biopsies performed from 1 January 2007 to 31 December 2013 (n = 1947). Patients were included when the biopsy was obtained following an MRI with a diffuse abnormal bone marrow signal. Patients who underwent MRI for suspected malignancy were excluded. Histological and cytological results of the bone marrow examinations were analysed. RESULTS: 15 of the 1947 bone marrow biopsies (0.77%) were performed because of diffuse signal alterations on MRI. In seven of these 15 bone marrow biopsies (47%) a clinically important haematological disorder was found. Eight patients had a normal bone marrow evaluation. CONCLUSION: Based on this retrospective study, a bone marrow examination in patients with incidentally detected diffuse signal alterations should be considered to exclude haematological pathology. Prospective studies have to be performed to further investigate the best diagnostic strategy.

Antenatal ureaplasma infection impairs development of the fetal ovine gut in an IL-1-dependent manner.

Ureaplasma infection of the amniotic cavity is associated with adverse postnatal intestinal outcomes. We tested whether interleukin-1 (IL-1) signaling underlies intestinal pathology following ureaplasma exposure in fetal sheep. Pregnant ewes received intra-amniotic injections of ureaplasma or culture media for controls at 3, 7, and 14 d before preterm delivery at 124 d gestation (term 150 d). Intra-amniotic injections of recombinant human interleukin IL-1 receptor antagonist (rhIL-1ra) or saline for controls were given 3 h before and every 2 d after Ureaplasma injection. Ureaplasma exposure caused fetal gut inflammation within 7 d with damaged villus epithelium and gut barrier loss. Proliferation, differentiation, and maturation of enterocytes were significantly reduced after 7 d of ureaplasma exposure, leading to severe villus atrophy at 14 d. Inflammation, impaired development and villus atrophy of the fetal gut was largely prevented by intra-uterine rhIL-1ra treatment. These data form the basis for a clinical understanding of the role of ureaplasma in postnatal intestinal pathologies.