Rituximab for eosinophilic granulomatosis with polyangiitis: a systematic review of observational studies.

OBJECTIVE: To analyse the available evidence about the use of rituximab (RTX) and other biologic agents in eosinophilic granulomatosis with polyangiitis (EGPA) patients and to provide useful findings to inform the design of future, reliable clinical trials. METHODS: A systematic review was performed. A systematic search was conducted in PubMed/MEDLINE, Scopus, Web of Science and the Cochrane library databases on RTX, and an extensive literature search was conducted on other biologic agents. RESULTS: Forty-five papers pertinent to our questions were found: 16 retrospective cohort studies, 8 case series, 3 prospective cohort studies and 18 single case reports, for a total of 368 EGPA patients. More than 80% of evaluable patients achieved complete or partial remission with a tendency towards a higher rate of complete response in the pANCA-positive subgroup. CONCLUSION: Although the majority of the evaluable EGPA patients treated with RTX appears to achieve complete remission, we strongly believe that a number of sources of heterogeneity impair a clear interpretation of results and limit their transferability in clinical practice. Differences in design, enrolment criteria, outcome definition and measurement make a comparison among data obtained from studies on RTX and other biologic agents unreliable.

Veno-occlusive Disease in HSCT Patients: Consensus-based Recommendations for Risk Assessment, Diagnosis, and Management by the GITMO Group.

Variation in clinical practice affects veno-occlusive disease management, mainly in patients who undergo allogeneic hematopoietic stem cell transplantation. Disputes about diagnostic criteria, treatment, and prophylaxis, due to the lack of high-quality data, are at the base of this variability. With the aim of limiting inconsistency in clinical care, thus improving both patient outcomes and data collection reliability, the Italian Society of Stem cell transplant (Gruppo Italiano Trapianto Midollo Osseo e Terapia Cellulare) launched a collaborative effort to formulate recommendations based on integration of available evidence and expert's consensus. A systematic method, according to US National Institute of Health guidelines and Italian National System for Guidelines, was used. Twenty-nine recommendations were approved with a strong (20) or weak (9) level of agreement, while 26 were rejected. In particular, the panel pointed out the need to achieve an early diagnosis, encouraging the adoption of European Society for Blood and Marrow Transplantation criteria and the prompt use of ultrasonography. Moreover, our experts strongly recommended in favor of prophylactic use of ursodeoxycholic acid. As soon as a veno-occlusive disease diagnosis is established, treatment with defibrotide should be started for at least 21 days. A number of areas of uncertainty, particularly concerning risk stratification and use of diagnostic tools such as elastography has been identified and discussed.

Clinical and patient reported outcomes of the multidisciplinary management in patients with inflammatory bowel disease-associated spondyloarthritis.

OBJECTIVE: Arthritis is the most frequent extra-intestinal manifestation in patients with inflammatory bowel diseases (IBD). The coexistence of intestinal and articular inflammation advocates the need for a multidisciplinary management of patients with IBD-associated spondyloarthritis. METHODS: Consecutive IBD patients were evaluated jointly by the gastroenterologist and the rheumatologist in a combined clinic. All the patients were assessed and screened for articular involvement, disease activity and health related quality of life. After the prescription of a shared treatment, patients with spondyloarthritis were followed up for 24 months. RESULTS: Two hundred sixty-two IBD patients, including 80 who were classified as affected by spondyloarthritis according to the ASAS criteria, were included in the study. At baseline, patients with both IBD and spondyloarthritis showed worse quality of life in both the physical and mental domains. The multidisciplinary management provided a significant improvement of gastrointestinal and articular manifestations, as well as the health-related quality of life. Moreover, global and gastrointestinal-specific quality of life significantly correlated with articular disease activity. CONCLUSION: The multidisciplinary management significantly improves both articular and gastrointestinal disease activities and the quality of life of patients with IBD-associated spondyloarthritis. An appropriate screening strategy and the integrated management of these patients should be encouraged and employed in clinical practice.

An Early Tailored Approach Is the Key to Effective Rehabilitation in the Intensive Care Unit.

OBJECTIVE: To investigate the effectiveness, feasibility, and safety of an evidence-based rehabilitation care pathway in the intensive care unit (ICU) in different patient populations. DESIGN: Observational prospective cohort study, with retrospective controls. SETTING: ICUs of a university hospital. PARTICIPANTS: Patients admitted between April 1, 2015, and June 30, 2015, were compared to a retrospective cohort admitted to the same ICUs during the same 3-month period in 2014. The number of patients studied (N=285) included 152 in the prospective group and 133 in the retrospective group. INTERVENTIONS: The prospective cohort benefited of a rehabilitation care pathway based on (1) interdisciplinary teamwork; (2) early customized and goal-oriented rehabilitation; (3) daily functional monitoring and treatment revision; (4) agreed discharge policy; and (5) continuity of care. The retrospective cohort underwent usual care. MAIN OUTCOME MEASURES: Included the following: (1) proportions of patients undergoing rehabilitation team evaluation; (2) latency between patient admission to ICUs and rehabilitation team assessment; (3) proportions of patients undergoing rehabilitation treatment during ICU stay; (4) latency between the patient admission to ICUs and rehabilitation start; (5) ICU stay and total acute hospital stay; and (5) proportion of ventilator-free days out of ICU stay. RESULTS: The novel rehabilitation care pathway led to (1) an increased proportion of patients receiving rehabilitative assessment (P<.0001); (2) a decreased latency from ICU admission to both rehabilitation team assessment and rehabilitation start (P<.0001); (3) an increased proportion of patients undergoing rehabilitation (P<.0001); (4) a shorter length of stay in ICUs (P<.0001) and in hospital (P=.047); and (5) a shorter mechanical ventilation duration (P<.02). A direct relationship between rehabilitation start latency and ICU length of stay was observed. CONCLUSIONS: An early, interdisciplinary team approach, providing a customized dynamic planning of physiotherapy programs, increases ventilator-free time and reduces total hospital stay, especially in patients admitted to the ICU after general surgery. This rehabilitation care pathway can be generalized to different geopolitical scenarios, being feasible, safe and cost effective.

Sustained clinical response after single course of rituximab as first-line monotherapy in adult-onset asthma and periocular xanthogranulomas syndrome associated with IgG4-related disease: A case report.

RATIONALE: IgG4-related disease (IgG4-RD) is an emerging immune-mediated disease characterized by multi-organ involvement and variable clinical behavior. PATIENT CONCERNS: We describe the case of a 50-year-old woman affected by a rare variant of IgG4-RD, characterized by eyelid xanthelasmas, adult-onset asthma and salivary and lacrimal glands enlargement. Multiple lymphadenopathies and a pulmonary mass were present at initial evaluation. INTEVENTIONS: After a single course of rituximab (2g in 2 refracted doses), an almost complete clinical remission was achieved without chronic steroid administration. OUTCOMES: Magnetic resonance imaging (MRI), high-resolution computed tomography (HRCT) of the thorax, and positron emission tomography (18FDG-PET-CT) confirmed good response to treatment. Circulating plasmablasts dropped to undetectable levels as well. Xanthelasmas only remained unchanged. Remission persisted at 1-year follow-up. LESSONS: Steroid therapy is still considered standard first-line therapy in IgG4-RD. However, high doses are generally required and relapses are common during the tapering phase. Rituximab is a well described steroid-sparing strategy, so far reserved to refractory cases only. In our experience, rituximab has been used as first-line monotherapy, showing great and sustained efficacy and optimal tolerability. The peculiar variant of IgG4-RD affecting our patient, the relatively low baseline plasmablast concentration, and the early placement of rituximab therapy may have facilitated the good response.

Tocilizumab in the treatment of patients with rheumatoid arthritis in real clinical practice: results of an Italian observational study.

OBJECTIVES: To describe the effectiveness and safety of tocilizumab (TCZ), an interleukin-6 receptor inhibitor, in a cohort of patients with rheumatoid arthritis (RA) recruited in clinical practice. METHODS: TRUST was an observational study in RA patients who started treatment with TCZ in the 6 months prior to site activation and were still on treatment at start of study; patients were followed up to 12 months after the first TCZ infusion. RESULTS: 322 RA patients were enrolled in 59 Italian centres (mean age: 55.8 years; mean disease duration: 120.5 months; baseline DAS28: 5.3). After 6 months of TCZ treatment, patients achieving low disease activity (DAS28 ≤3.2; 57.52%) or disease remission (DAS28 <2.6; 38.05%) were 216 out of 226 patients with available DAS28 (p<0.001). No statistically significant differences were found in mean DAS28 and HAQ score changes from baseline (start of TCZ treatment) to study end between patients previously inadequately responding to disease-modifyinganti-rheumatic drugs (DMARD-IR) or to DMARDs plus tumour necrosis factor inhibitors (DMARD +TNFi-IR): both patient populations responded to TCZ. A statistically significant decrease in mean VAS Fatigue score (48.4 vs. 34.7; p=0.0025) at month 6 was observed. In patients treated with TCZ as monotherapy (32.61%), DAS28, VAS fatigue and HAQ scores decreased from baseline to any post-baseline time point. Overall, 62 patients (19.3%) prematurely discontinued TCZ treatment, 24 (7.5%) for safety reasons. Drug-related adverse events occurred in 92 patients (28.6%) (mostly 3 hypercholesterolaemia and leucopenia) and drug-related serious adverse events in 11 patients (3.4%). CONCLUSIONS: This study confirms the good effectiveness and safety profile of TCZ in real life RA patient care.

Successful treatment of a Caucasian case of multifocal Castleman's disease with TAFRO syndrome with a pathophysiology targeted therapy - a case report.

BACKGROUND: Castleman-Kojima disease (TAFRO Syndrome) is characterized by Thrombocytopenia, Anasarca, myeloFibrosis, Renal dysfunction, Organomegaly, multiple lymphadenopathy and histopathology pattern of atypical Castleman's disease (CD). Only few cases of this recently identified unique variant of Multicentric CD (MCD) are described in literature, all Japanese. It therefore poses serious diagnostic and therapeutic challenges. CASE DESCRIPTION: We describe a 21 year old woman with fever, asthenia, bilateral pleural effusion, ascites, hypoalbuminemia, severe thrombocytopenia, anemia, renal failure and proteinuria, whereas microbiological tests, immune serology (except ANA) and bone marrow biopsy were all negative. A CT-scan showed multiple lymphadenopathy and tissue samplings of mediastinal lymph nodes was compatible with a mixed-type CD. The diagnosis of MCD with TAFRO syndrome was made, but after an initial improvement with high dose corticosteroid therapy, clinical and laboratory features worsened. Based upon the high serum IL-6 levels and the high number of CD20-lymphocytes in lymph nodes tissue, we started tocilizumab (partial benefit), followed by rituximab combined with CVP (cyclophosphamide, vincristine and prednisone) chemotherapy, achieving a complete response. A total of six cycles of R-CVP were administered monthly, followed by maintenance with monthly rituximab. A complete remission persists at the 12th month of follow-up. CONCLUSIONS: In patients with massive immune system activation and lymphadenopathy it is mandatory to rule out Castleman-Kojima disease. In our patient a therapy aimed at the prominent pathophysiological abnormalities has been successful so far. However, since the rarity of TAFRO Syndrome, a multicenter registry is strongly desirable for a better understanding of the disease mechanisms, hopefully leading to evidence-based therapeutic choices.

Systemic sclerosis (scleroderma) and cancer risk: systematic review and meta-analysis of observational studies.

OBJECTIVES: A higher incidence of cancer in scleroderma patients compared with the general population has been suggested by several observational studies, reporting, however, different estimates. Therefore, we aimed to perform a systematic review and meta-analysis to definitely assess this association. METHODS: We searched MEDLINE and Embase for all original articles of observational studies on cancer incidence in scleroderma patients without language restriction published up to December 2011. Two independent authors reviewed all titles/abstracts and retrieved detailed full-text of potentially relevant articles to identify studies according to predefined selection criteria. Summary estimates were derived using random-effects model and reported as relative risk (RR). Publication bias was evaluated by trim and fill analysis. RESULTS: From articles initially identified, 16 original studies, involving more than 7000 patients, were included in the present review. Compared with the general population, the summary RR to develop all invasive cancers in scleroderma patients was 1.75 (95% CI 1.41, 2.18). The results for selected cancer sites indicated a strong association with lung cancer (RR 4.35; 95% CI 2.08, 9.09), and a significant increased risk also for haematological neoplasms (RR 2.24; 95% CI 1.53, 3.29). The relation with breast cancer, suggested in some previous epidemiological studies, was not confirmed (RR 1.05; 95% CI 0.86, 1.29). CONCLUSION: The present meta-analysis, the first on scleroderma and cancer risk, provides definite estimates on the association between scleroderma and cancer.

Management of minor head injury in patients receiving oral anticoagulant therapy: a prospective study of a 24-hour observation protocol.

STUDY OBJECTIVE: Patients receiving warfarin who experience minor head injury are at risk of intracranial hemorrhage, and optimal management after a single head computed tomography (CT) scan is unclear. We evaluate a protocol of 24-hour observation followed by a second head CT scan. METHODS: In this prospective case series, we enrolled consecutive patients receiving warfarin and showing no intracranial lesions on a first CT scan after minor head injury treated at a Level II trauma center. We implemented a structured clinical pathway, including 24-hour observation and a CT scan performed before discharge. We then evaluated the frequency of death, admission, neurosurgery, and delayed intracranial hemorrhage. RESULTS: We enrolled and observed 97 consecutive patients. Ten refused the second CT scan and were well during 30-day follow-up. Repeated CT scanning in the remaining 87 patients revealed a new hemorrhage lesion in 5 (6%), with 3 subsequently hospitalized and 1 receiving craniotomy. Two patients discharged after completing the study protocol with 2 negative CT scan results were admitted 2 and 8 days later with symptomatic subdural hematomas; neither received surgery. Two of the 5 patients with delayed bleeding at 24 hours had an initial international normalized ratio greater than 3.0, as did both patients with delayed bleeding beyond 24 hours. The relative risk of delayed hemorrhage with an initial international normalized ratio greater than 3.0 was 14 (95% confidence interval 4 to 49). CONCLUSION: For patients receiving warfarin who experience minor head injury and have a negative initial head CT scan result, a protocol of 24-hour observation followed by a second CT scan will identify most occurrences of delayed bleeding. An initial international normalized ratio greater than 3 suggests higher risk.

A management of blunt thoracic trauma in an emergency department observation unit: pre-post observational study.

BACKGROUND: The best management of patients with isolated blunt thoracic trauma at high risk of pulmonary complications (HRPC-BTT: ≥3 isolated rib fractures, sternal fracture, single or few pulmonary contusions or minimal pneumothorax) is still unclear. We compared efficacy and cost-effectiveness of a new clinical pathway involving an Emergency Department Observation Unit (EDOU) with routine care. DESIGN: Retrospective before-after study. SETTING: Level II Trauma Center within a Regional Teaching Hospital. PARTICIPANTS: A consecutive series of patients with HRPC-BTT. INTERVENTIONS: a new clinical pathway involving EDOU was implemented. MAIN OUTCOMES: Death rate, tube thoracostomy, and re-admission of discharged patients. Hospital admission rate, length of hospital occupancy, overall costs, and cost-effectiveness were also compared in pre- and post-EDOU period. RESULTS: Two hundred forty patients were eligible for the study: 110 patients in the pre-EDOU period and 130 in the post-EDOU period. Thirteen (12%) of the treated patients were re-admitted to the ED in the pre-EDOU period compared with only five (4%) when the EDOU was available (p = 0.03). The rate of tube thoracostomy performed in admitted patients significantly increased after EDOU implementation: 1 of 54 (1.9%) versus 4 of 32 (12.5%; p < 0.05). The rate of hospitalization decreased from 49% in the pre-EDOU period to 24% in the post-EDOU period (p < 0,005) and the length of stay in hospital in the pre-EDOU period was longer than in the EDOU period: mean 94.7 ± 79.6 versus 65.7 ± 60.6, respectively (p < 0.02). Cost analysis revealed no relevant change in cost-effectiveness per patient (median; interquartile range): €487; €103 to 1959 versus €616; €124 to 1455, respectively, in the pre- and post-EDOU period. CONCLUSIONS: In managing patients affected by HRPC-BTT, a clinical pathway involving the EDOU seems to be more effective than routine care with little impact on cost.

[Topic efficacy of ialuronic acid associated with argentic sulphadiazine (Connettivina Plus) in the treatment of pressure sores: a prospective observational cohort study]. / Efficacia dell'acido ialuronico associato alla sulfadiazina argentica (Connettivina Plus) nel trattamento delle lesioni da pressione: uno studio di coorte osservazionale prospettico.

RATIONALE: The aim of this observational study was to evaluate the efficacy, tolerability and methods of application of ialuronic acid associated with argentic sulphadiazine (Connettivina Plus) in routine clinical activity, on a target of "complex" patients with pressure sores, for the most realistic assessment possible. The study comprised 127 patients hospitalized between January 2006 and December 2007, who received ialuronic acid associated with argentic sulphadiazine in addition to the standard treatment. Inclusion criteria were th presence of at least one stage 2 or 3 pressure sore (NPUAP '89 classification), pressure sore that the researcher had already decided to treat using ialuronic acid associated with argentic sulphadiazine , according to hospital protocol, area of the lesion less than 25cm2, patient age 18 years or more, informed patient consensus. Patients with these characteristics were , however, excluded if they did not provide written consent or if they had one of the following: presence of pressure sores with escara, concomitant neoplastic disease, concomitant insulin-dependent diabetes or other pathologies that interfere with skin regeneration, allergic diasthesis (acclaimed or presumed) to ialuronic acid - argentic sulphadiazine, inability / refusal to undergo all the subsequent controls required by the study. RESULTS: Improvement or complete healing of the pressure sores was observed in 67% of patients at early follow-up (10 days), increasing to 76% and 87% at 20 and 35 day controls respectively. The Push tool further improved in patients who carried on treatment. CONCLUSIONS: Use of ialuronic acid associated with argentic sulphadiazine was effective for treating grade 2-3 pressure sores in patients with chronic lesions and its efficacy was confirmed in association with both advanced and traditional types of medication.

Acute myocarditis associated with adenoviral infection in a patient with scleroderma.

We describe a 40-year-old man with limited scleroderma who presented with acute heart failure following a flu-like illness. He was known to have incomplete left anterior bundle branch block, initial isolated pulmonary hypertension with enlarged right atrium, and no pulmonary fibrosis. He received therapy for acute heart failure and was transferred to a scleroderma centre for specific treatment of scleroderma cardiomyopathy. Investigations showed raised inflammatory markers and diffuse hyperechogenic thickening of the myocardium on echocardiography. Contrast-enhanced (Gd-DOTA) cardiovascular magnetic resonance imaging (CV-MRI) showed multiple areas of non-homogeneous delayed hyperenhancement in the left ventricle, suggestive of myocarditis. Antiadenovirus IgM antibodies were detected with a titer consistent with recent infection. Six weeks later a repeat Gd-DOTA CV-MRI showed an almost complete resolution of the areas of hyperenhancement and there was a significant reduction in the adenovirus antibody titer with serological conversion to IgG. To our knowledge this is the first report of viral myocarditis in scleroderma. Infections are important causes of morbidity and mortality in this disease and should always be included in the differential diagnosis of cardiac symptoms. We propose that contrast-enhanced CV-MRI is valuable in a non-invasive diagnosis of heart disease in patients with scleroderma.