Is tocilizumab a potential therapeutic option for refractory unicentric Castleman disease?

Castleman disease is a rare lymphoproliferative disorder with 2 distinctly defined clinical forms. While multicentric Castleman disease (UCD) poses a potential therapeutic challenge, unicentric variant has historically been considered curable with surgical resection. Hence, little is known to guide management of patients with UCD, refractory to surgical resection and combination chemotherapy. We present a case of a patient, negative for HIV and HHV-8, who had an unsuccessful surgical intervention and no response to radiotherapy and chemotherapy. He had severe paraneoplastic pemphigus and was treated with tocilizumab, an anti-interleukin-6 receptor monoclonal antibody that has demonstrated good response rates in multicentric Castleman disease but demonstrated no clinical response despite 2 months of treatment. Our report is the first to describe a lack of response to tocilizumab in the rare setting of refractory UCD and discuss potential for distinct disease biology.

Extending the course of intravenous antibiotics in adult patients with cystic fibrosis with acute pulmonary exacerbations.

Most severe pulmonary exacerbations (PExs) in adult patients with cystic fibrosis (CF) are treated with 2 week of intravenous (IV) antibiotics. At occasions, the treatment is extended. The morbidity and the cost of extending the treatment are considerable. Risk factors and the outcome of extending the course of treatment have not been formally investigated. This was a prospective study. Decision to extend the course of antibiotics was made in patients who were not deemed to have responded to the initial 14 days of treatment. Risk factors examined for extending the course were site of treatment (home or hospital), CF symptom score, body mass index (BMI), forced expiratory volume in the first second (FEV1) and C-reactive protein (CRP) at days 1 and 14 of the treatment. The following outcome measures were assessed for PExs requiring prolongation of treatment: FEV1, BMI, CF symptom score, CRP and number of days until the following PExs. PExs that were treated with 14 day course were used for comparison. Of all the PExs, 22.9% needed extension of treatment beyond day 14. Compared with PExs needing 14 days of antibiotics, CF symptom score, FEV1 and CRP at day 14 were worse in those who had to have the course extended. Extending the course of IV antibiotics to 21 days improved symptom score, but not any of the other outcome measures, including the number of days until the next PEx. Extending the course beyond 21 days did not result in improvement in any outcome measure. PExs in patients with worse lung disease and greater residual symptoms and lung inflammation at day 14 of antibiotic treatment were associated with the extension of the course of IV antibiotics. Prolonging the treatment to 21 days improved symptoms, but did not result in improvement in any other short-term or lung outcome measures.

Factors associated with a shorter time until the next pulmonary exacerbation in adult patients with cystic fibrosis.

Time until the subsequent exacerbation (PEx) in cystic fibrosis (CF) is a significant health outcome and one of the significant end points in clinical trials. Risk factors associated with shorter time until the next exacerbation (TUNE) have not been reported. This is a prospective study. TUNE was the number of days from the end of intravenous (IV) antibiotic treatment of a PEx until the day of start of IV antibiotics for the following PEx. Factors assessed were age, gender, site of treatment, CF-related diabetes (CFRD), allergic bronchopulmonary aspergillosis (ABPA) and infection with Pseudomonas aeruginosa (PA). In addition, we examined parameters obtained at day 14 of treatment including forced expiratory volume in the first second (FEV1), body mass index, CF respiratory symptom score, C-reactive protein (CRP) and serum cytokines. A total of 170 exacerbations in 58 adult CF patients (27 female), mean (SD) age 25.8 (6.7) years were analysed. When analysing individual variables, patients with lower FEV1, greater symptom score and higher CRP at the end of exacerbation were associated with shorter TUNE. Patients with ABPA and CFRD had a shorter TUNE than those without. When applying multiple regression analysis, factors associated with shorter TUNE were older age and lower day-14 FEV1 values. Shorter periods until the following PEx are expected in older CF patients and those with lower FEV1 at the end of course of treatment. When these risk factors are present, there may be a justification to take therapeutic steps to increase the time until the following PEx.

Home intravenous antibiotic treatment for acute pulmonary exacerbations in cystic fibrosis - Is it good for the patient?

There is a worldwide drive for the home management of chronic respiratory diseases. With the widespread use of home intravenous (IV) treatment for cystic fibrosis (CF) pulmonary exacerbations (PExs), evidence pointing to an inferior outcome of care for home-treated patients in comparison to hospital-treated patients is a cause of concern. Currently, patients who self-administer IV antibiotics at home are provided with equipment and instructions on the use of antibiotics. Policies vary; but in most UK centers, these patients are then followed up by the multidisciplinary team only on days 1, 7 and 14 of the treatment course. We aimed to review the current published literature in search for evidence for the value and the shortfalls of self-administered IV treatment at home for acute PExs in CF patients in comparison to conventional hospital treatment. We searched the electronic database system Medline for published papers regarding studies comparing home- and hospital-based IV antibiotic treatment for both adult and pediatric CF patients. Sixteen studies were identified and grouped into those that showed a similar outcome between home and hospital treatment and those that showed an inferior outcome for home management. Most studies were retrospective or inadequately powered to provide clear answers. Ideally, outcome of care for home treatment should be at least equal to outcome for hospital treatment. Extensive efforts should be made to standardize therapies preserving the advantages of home management and addressing the perceived reasons for an inferior outcome. Until further studies provide definitive answers, treatment at home should be reserved for adequately selected patients and individualized depending on the unique settings of each CF center and specific patients' requirements. There is great need for a prospective randomized controlled trial comparing home and hospital treatments in order to clarify this matter.