Clinical and laboratory characteristics in juvenile-onset systemic lupus erythematosus across age groups.

BACKGROUND: Systemic lupus erythematous (SLE) is a systemic autoimmune/inflammatory condition. Approximately 15-20% of patients develop symptoms before their 18th birthday and are diagnosed with juvenile-onset SLE (JSLE). Gender distribution, clinical presentation, disease courses and outcomes vary significantly between JSLE patients and individuals with adult-onset SLE. This study aimed to identify age-specific clinical and/or serological patterns in JSLE patients enrolled to the UK JSLE Cohort Study. METHODS: Patient records were accessed and grouped based on age at disease-onset: pre-pubertal (≤7 years), peri-pubertal (8-13 years) and adolescent (14-18 years). The presence of American College of Rheumatology (ACR) classification criteria, laboratory results, disease activity [British Isles Lupus Assessment Group (BILAG) and Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K) scores] and damage [Systemic Lupus International Collaborating Clinics (SLICC) damage index] were evaluated at diagnosis and last follow up. RESULTS: A total of 418 JSLE patients were included in this study: 43 (10.3%) with pre-pubertal disease onset; 240 (57.4%) with peri-pubertal onset and 135 (32.3%) were diagnosed during adolescence. At diagnosis, adolescent JSLE patients presented with a higher number of ACR criteria when compared with pre-pubertal and peri-pubertal patients [pBILAG2004 scores: 9(4-20] vs. 7(3-13] vs. 7(3-14], respectively, p = 0.015] with increased activity in the following BILAG domains: mucocutaneous (p = 0.025), musculoskeletal (p = 0.029), renal (p = 0.027) and cardiorespiratory (p = 0.001). Furthermore, adolescent JSLE patients were more frequently ANA-positive (p = 0.034) and exhibited higher anti-dsDNA titres (p = 0.001). Pre-pubertal individuals less frequently presented with leukopenia (p = 0.002), thrombocytopenia (p = 0.004) or low complement (p = 0.002) when compared with other age groups. No differences were identified in disease activity (pBILAG2004 score), damage (SLICC damage index) and the number of ACR criteria fulfilled at last follow up. CONCLUSIONS: Disease presentations and laboratory findings vary significantly between age groups within a national cohort of JSLE patients. Patients diagnosed during adolescence exhibit greater disease activity and "classic" autoantibody, immune cell and complement patterns when compared with younger patients. This supports the hypothesis that pathomechanisms may vary between patient age groups.

Outcomes following mycophenolate mofetil versus cyclophosphamide induction treatment for proliferative juvenile-onset lupus nephritis.

BACKGROUND: Juvenile-onset systemic lupus erythematosus (JSLE) is more severe than adult-onset disease, including more lupus nephritis (LN). Despite differences in phenotype/pathogenesis, treatment is based upon adult trials. This study aimed to compare treatment response, damage accrual, time to inactive LN and subsequent flare, in JSLE LN patients treated with mycophenolate mofetil (MMF) versus intravenous cyclophosphamide (IVCYC). METHODS: UK JSLE Cohort Study participants, ≤16 years at diagnosis, with ≥4 American College of Rheumatology criteria for SLE, with class III or IV LN, were eligible. Mann-Whitney U tests, Fisher's exact test and Chi-squared tests were utilized for statistical analysis. RESULTS: Of the patients, 34/51 (67%) received MMF, and 17/51 (33%) received IVCYC. No significant differences were identified at 4-8 and 10-14 months post-renal biopsy and last follow-up, in terms of renal British Isles Lupus Assessment Grade scores, urine albumin/creatinine ratio, serum creatinine, ESR, anti-dsDNA antibody, C3 levels and patient/physician global scores. Standardized Damage Index scores did not differ between groups at 13 months or at last follow-up. Inactive LN was attained 262 (141-390) days after MMF treatment, and 151 (117-305) days following IVCYC ( p = 0.17). Time to renal flare was 451 (157-1266) days for MMF, and 343 (198-635) days for IVCYC ( p = 0.47). CONCLUSION: This is the largest study to date investigating induction treatments for proliferative LN in children, demonstrating comparability of MMF and IVCYC.

Targeted next-generation sequencing identifies clinically relevant mutations in patients with chronic neutrophilic leukemia at diagnosis and blast crisis.

PURPOSE: Chronic neutrophilic leukemia is a rare form of myeloproliferative neoplasm characterized by mature neutrophil hyperleukocytosis. The majority of patients harbor somatic mutations of CSF3R gene and are potentially amenable to targeted therapy with JAK inhibitors. The incidence and clinical significance of additional mutations requires clarification. MATERIALS AND METHODS: A next-generation sequencing approach for myeloid malignancy-associated mutations was applied to diagnostic and matched blast crisis samples from four chronic neutrophilic leukemia patients. RESULTS: Next-generation sequencing confirmed the CSF3R T618I in all patients with identification of concurrent SRSF2, SETBP1, NRAS and CBL mutations at diagnosis. At blast crisis, clonal evolution was evidenced by an increased CSF3R T618I allele frequency and by loss or acquisition of CBL and NRAS mutations. CONCLUSION: The diagnostic utility of a targeted next-generation sequencing approach was clearly demonstrated with the identification of additional mutations providing the potential for therapeutic stratification of chronic neutrophilic leukemia patients.

Evaluation of the ACR and SLICC classification criteria in juvenile-onset systemic lupus erythematosus: a longitudinal analysis.

Objectives The Systemic Lupus International Collaborating Clinics (SLICC) group proposed revised classification criteria for systemic lupus erythematosus (SLICC-2012 criteria). This study aimed to compare these criteria with the well-established American College of Rheumatology classification criteria (ACR-1997 criteria) in a national cohort of juvenile-onset systemic lupus erythematosus (JSLE) patients and evaluate how patients' classification criteria evolved over time. Methods Data from patients in the UK JSLE Cohort Study with a senior clinician diagnosis of probable evolving, or definite JSLE, were analyzed. Patients were assessed using both classification criteria within 1 year of diagnosis and at latest follow up (following a minimum 12-month follow-up period). Results A total of 226 patients were included. The SLICC-2012 was more sensitive than ACR-1997 at diagnosis (92.9% versus 84.1% p < 0.001) and after follow up (100% versus 92.0% p < 0.001). Most patients meeting the SLICC-2012 criteria and not the ACR-1997 met more than one additional criterion on the SLICC-2012. Conclusions The SLICC-2012 was better able to classify patients with JSLE than the ACR-1997 and did so at an earlier stage in their disease course. SLICC-2012 should be considered for classification of JSLE patients in observational studies and clinical trial eligibility.

Incidence and significance of FLT3-ITD and NPM1 mutations in patients with normal karyotype acute myeloid leukaemia.

BACKGROUND: Acute myeloid leukaemia (AML) is a heterogeneous clonal disorder of haematopoietic progenitor cells. Approximately half of all adult AML patients have a normal karyotype (NK-AML) and an intermediate risk prognosis. AIMS: To determine the incidence and prognostic significance of NPM1 and FLT3-ITD mutations in a population of patients with NK-AML. METHODS: FLT3-ITD and NPM1 mutation status was retrospectively sought in presentation samples from 44 NK-AML patients. RESULTS: FLT3-ITD and NPM1 mutations were detected in 45.5 and 54.5% of patients, respectively, allowing stratification according to genotype. CONCLUSIONS: FLT3-ITD and NPM1 mutation status can be defined in NK-AML. Prospective screening for these mutations is advocated in all NK-AML patients, as the genotype is of clinical importance when considering treatment options including stem cell transplantation.

Cloning and characterization of spliced fusion transcript variants of synovial sarcoma: SYT/SSX4, SYT/SSX4v, and SYT/SSX2v. Possible regulatory role of the fusion gene product in wild type SYT expression.

The synovial sarcoma translocation t(X;18)(p11.2; q11.2) results in the fusion of the SYT gene on chromosome 18 to exon 5 of either SSX1 or SSX2 genes on chromosome X. We recently reported that the SSX4 gene is also involved in such a translocation. In the present investigation we cloned and sequenced the full-length cDNA of SYT/SSX1, SYT/SSX2 and SYT/SSX4 from synovial sarcoma tissues. We isolated a novel fusion transcript type variant involving the fusion of SYT with exon 6 of the SSX4 gene (SYT/SSX4v). The SYT/SSX4 and SYT/SSX2 open reading frame also differed from previously reported SYT/SSX sequences by an in-frame addition of 93bp exon located in the junction between exon 7 and 8 of the SYT. This exon is identical to that reported for the murine SYT but has not been previously found in the human transcript. Two SYT transcripts, with and without the 93 bp exon, were co-expressed in mouse NIH3T3 cells, human malignant cells and human testis tissue, but not in human normal fibroblasts. Stable transfection of an SYT/SSX4 expression vector into human and murine cell lines correlated with a down-regulation of SYT transcripts. This was also observed in a synovial sarcoma tumor expressing SYT/SSX4. This suggests that the SYT/SSX fusion gene may regulate SYT expression from the normal allele and as such alter the normal function of SYT.

Teaching the use of walkers and canes.

Home care and hospice nurses frequently encounter patients who use assistive devices to safely remain mobile in their homes. Incorrectly used, these devices may contribute to falls. This article provides a review on the use and teaching of these devices to patients and caregivers. A physical therapist, occupational therapist, or rehabilitation nurse should be consulted for any questions about applying the guidelines in this article to patients.

ECG recorder distribution and hospital utilization.

Although use of the portable ECG recorder is commonplace, information on actual daily use in an acute care hospital is scarce. To determine whether machines are efficiently used, we attached timers to ECG recorders in 17 wards and clinics to collect data on the time of actual use. Usage ranged from 31 min/day in the coronary care unit to 0.7 min/day in the postpartum ward, and averaged 8.0 +/- 8 min/day for all locations. Seventy-five percent of the recorders were used less than 10 min/day and 25 percent of the recorders were used less than 2 min/day. On a per-bed basis they were used 0.8 +/- 1.4 min/day. Almost no correlation was found between the number of portable ECG recorders and number of beds in 20 teaching and 23 nonteaching hospitals. The number of beds ranged from 11 to 70 per ECG recorder in teaching hospitals and from 14 to 122 in nonteaching hospitals. Nonteaching hospitals averaged 59 +/- 26 beds per recorder; teaching hospitals averaged 34 +/- 17 beds per machine. Some ECG recorders seem to be markedly underutilized and some hospitals seem to be oversupplied with these devices. To reverse this, establishing an equipment committee to see that equipment is efficiently used is recommended.

In-house medical device maintenance.

The establishment of a medical engineering department in this 600-bed institution has proved to be cost-effective and has improved the hospital's environment.

Problems with telemetry monitoring systems.

The purchaser of telemetry monitoring systems for operating and recovery rooms has little information available on the practical aspects of ownership and usage. To explore this problem, we recorded 76 telemetry failures (both operator and machine failure) occurring over six months among 18 telemetry channels located in operating and recovery rooms. We experienced approximately one telemetry failure every three days or every 60 surgical procedures. Factory repairs were required on 29 transmitters and 19 receivers during a two-year period. We observed that 28% of the failures were attributable to lead and electrode problems, 25% to battery depletion, 22% to mechanical or electronic component failures, 12% to inappropriate control settings and frequency mismatching, and 13% to miscellaneous difficulties. The following problems were observed. Transmitters were dropped frequently and occasionally immersed in liquids. Thus, waterproofing is recommended for OR use, and lead-failure warning circuitry is mandatory. Inappropriate control settings and frequency mismatching led to a previously unrecognized hazard: that is, it is possible to receive and display ECG data from the wrong patient located in a distant room. (Stethoscopic monitoring can be used to confirm that the data being displayed are from the correct patient.) Battery failure can occur at inopportune times, e.g., during cardiac arrest. Transmitters are frequently "lost" because of their small size and high mobility. This study indicated to us that, in the operating room, telemetry is not desirable because of its high cost compared to hard wired systems, poor reliability, and the possible hazard of displaying data from the wrong patient if improperly used.