Risk factors and possible mechanisms of intravenous port catheter migration.

OBJECTIVE: To identify the risk factors for catheter migration and demonstrate possible mechanisms of this migration. DESIGN: Retrospective study. SETTING: Chang Gung Memorial Hospital, a tertiary medical centre in Taiwan. PATIENTS: Patients who underwent implantation of intravenous ports via the superior vena cava (SVC). INTERVENTIONS: Procedures involving catheter placement and re-intervention for catheter migration. MAIN OUTCOME MEASURES: The anatomic location of the catheter tip was confirmed by plain chest X-rays (postero-anterior view). From these plain radiographs, the distance (in cm) between the carina and catheter tip and the angle (in degrees) between the locking nut and catheter were measured. METHODS: A total of 1542 procedures related to intravenous port implantation were retrospectively reviewed but only procedures involving implantation via the SVC were included in the analysis. The study group was composed of 31 interventions because of catheter migration, while the control group consisted of 1475 implantation and re-intervention procedures except those involving catheter migrations. RESULTS: Shallow catheter-tip location (p < 0.0001) and the presence of lung cancer (p = 0.006) were risk factors for catheter migration. CONCLUSIONS: Shallow catheter-tip location and the presence of lung cancer are risk factors for catheter migration. Strategies that ensure low catheter-tip location and avoid increased thoracic pressure may be useful preventive measures.

Osimertinib plus platinum-pemetrexed in newly diagnosed epidermal growth factor receptor mutation-positive advanced/metastatic non-small-cell lung cancer: safety run-in results from the FLAURA2 study.

BACKGROUND: The phase III FLAURA2 (NCT04035486) study will evaluate efficacy and safety of first-line osimertinib with platinum-pemetrexed chemotherapy versus osimertinib monotherapy in epidermal growth factor receptor mutation-positive (EGFRm) advanced/metastatic non-small-cell lung cancer (NSCLC). The safety run-in, reported here, assessed the safety and tolerability of osimertinib with chemotherapy prior to the randomized phase III evaluation. PATIENTS AND METHODS: Patients (≥18 years; Japan: ≥20 years) with EGFRm locally advanced/metastatic NSCLC received oral osimertinib 80 mg once daily (QD), with either intravenous (IV) cisplatin 75 mg/m2 or IV carboplatin target area under the curve 5, plus pemetrexed 500 mg/m2 every 3 weeks (Q3W) for four cycles. Maintenance was osimertinib 80 mg QD with pemetrexed 500 mg/m2 Q3W until progression/discontinuation. The primary objective was to evaluate safety and tolerability of the osimertinib-chemotherapy combination. RESULTS: Thirty patients (15 per group) received treatment [Asian, 73%; female, 63%; median age (range) 61 (45-84) years]. Adverse events (AEs) were reported by 27 patients (90%): osimertinib-carboplatin-pemetrexed, 100%; osimertinib-cisplatin-pemetrexed, 80%. Most common AEs were constipation (60%) with osimertinib-carboplatin-pemetrexed and nausea (60%) with osimertinib-cisplatin-pemetrexed. In both groups, 20% of patients reported serious AEs. No specific pattern of AEs leading to dose modifications/discontinuations was observed; one patient discontinued all study treatments including osimertinib due to pneumonitis (study-specific discontinuation criterion). Hematologic toxicities were as expected and manageable. CONCLUSIONS: Osimertinib-chemotherapy combination had a manageable safety and tolerability profile in EGFRm advanced/metastatic NSCLC, supporting further assessment in the FLAURA2 randomized phase.

Atherogenic serum lipid profile is an independent predictor for gouty flares in patients with gouty arthropathy.

OBJECTIVE: Atherogenic serum lipid profile possesses pro-inflammatory properties and is associated with more active RA. While prevalent in patients with gout, whether atherogenic lipid profile is associated with gouty flares is unknown. This study aims to investigate whether atherogenic serum lipid predicts gouty flares in patients with gout. METHODS: Adult patients (age > or =21 yrs) who suffered from gout were prospectively followed between September 2006 and November 2007 and their demographic, clinical and laboratory data were collected. Episodes of gouty flares over this observation period were recorded and factors predictive of gouty flares were studied by regression models. RESULTS: Of the 100 patients, 80 were men, 65 were ethnic Chinese, 31 were Malay and the rest were Indian and Caucasian. The mean age and duration of gout (+/-S.D.) were 61.9 +/- 14.0 and 6.6 +/- 7.8 yrs, respectively. The mean serum uric acid and creatinine levels were 537.6 +/- 142.8 and 173.6 +/- 119.9 micromol/l, respectively. In univariate analysis, longer duration of gout, higher adjusted mean serum creatinine, lower adjusted mean fasting serum, total cholesterol and high-density lipoprotein cholesterol (HDL-C) levels were associated with gouty flares. After adjustment for potential confounders in multivariate regression models, longer duration of gout and lower adjusted mean fasting serum HDL-C level remained independently predictive of gouty flares. CONCLUSIONS: Low serum high-density lipoprotein cholesterol level was an independent predictor for gouty flares. Whether optimizing serum HDL-C level can benefit patients with gout in terms of reducing gouty flares needs to be addressed by controlled trials.

Neuropsychiatric lupus and reversible posterior leucoencephalopathy syndrome: a challenging clinical dilemma.

Reversible posterior leucoencephalopathy syndrome (RPLS) has been increasingly recognized and reported in the literature. While the condition has been well described in patients with acute hypertension, pre-eclampsia, eclampsia, post-transplantation and chemotherapy, RPLS has been increasingly identified in patients with autoimmune diseases such as systemic lupus erythematosus (SLE). Though experience in the diagnosis and management of RPLS in patients with SLE is likely accumulating, few have systematically worked out the strategy to distinguish RPLS from neuropsychiatric SLE (NPSLE) and lupus-related complications of the central nervous system (CNS). Prompt recognition of, and differentiation between, these conditions is essential since their clinical presentations substantially overlap and yet their management strategy and subsequent outcomes can be entirely different. Indeed, inappropriate treatment such as augmentation of immunosuppression may be detrimental to patients with RPLS. A high index of suspicion of RPLS, prompt magnetic resonance imaging of the brain, including diffusion imaging, exclusion of CNS infection and metabolic derangement, a comprehensive medication review accompanied by timely and aggressive control of blood pressure and seizure are keys to successful management of RPLS. Such treatment strategy ensures a very high chance of total neurological recovery in lupus patients with RPLS.

Anti-leukemic activity and tolerability of anti-human CD47 monoclonal antibodies.

CD47, a broadly expressed cell surface protein, inhibits cell phagocytosis via interaction with phagocyte-expressed SIRPα. A variety of hematological malignancies demonstrate elevated CD47 expression, suggesting that CD47 may mediate immune escape. We discovered three unique CD47-SIRPα blocking anti-CD47 monoclonal antibodies (mAbs) with low nano-molar affinity to human and cynomolgus monkey CD47, and no hemagglutination and platelet aggregation activity. To characterize the anti-cancer activity elicited by blocking CD47, the mAbs were cloned into effector function silent and competent Fc backbones. Effector function competent mAbs demonstrated potent activity in vitro and in vivo, while effector function silent mAbs demonstrated minimal activity, indicating that blocking CD47 only leads to a therapeutic effect in the presence of Fc effector function. A non-human primate study revealed that the effector function competent mAb IgG1 C47B222-(CHO) decreased red blood cells (RBC), hematocrit and hemoglobin by >40% at 1 mg/kg, whereas the effector function silent mAb IgG2σ C47B222-(CHO) had minimal impact on RBC indices at 1 and 10 mg/kg. Taken together, our findings suggest that targeting CD47 is an attractive therapeutic anti-cancer approach. However, the anti-cancer activity observed with anti-CD47 mAbs is Fc effector dependent as are the side effects observed on RBC indices.

HLA and systemic lupus erythematosus in Chinese.

Seventy-five unrelated Chinese SLE patients were HLA typed and subdivided into mild and severe disease. The HLA-B13 was associated with mild disease. Fourteen of 30 (46.7%) mild disease patients had B13 compared to 63/330 (19.1%) normal subjects (p less than 0.0005, corrected p less than 0.013, RR = 3.7). The HLA-B17 on the other hand was observed in 29% of 45 severe disease patients compared to 13.9% of 330 normal subjects (p less than 0.01, RR = 2.5). The frequency of HLA-B17 in 11 patients who died was even higher (45.5%).

NSAID-induced gastrointestinal damage. Epidemiology, risk and prevention, with an evaluation of the role of misoprostol. An Asia-Pacific perspective and consensus.

The problem of nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal toxicity was reviewed by members of the Asia Pacific League of Associations for Rheumatology (APLAR) in a consensus conference in September 1992. This paper by the participants presents the consensus conclusions incorporating knowledge from recent publications. There had been a high level of concern that much of the toxicity had resulted from extensive and indiscriminate prescribing of NSAIDs. The implementation of evidence-based guidelines was considered likely to be able to effect a substantial reduction in toxicity without significant loss of overall therapeutic benefit. The evidence from which such guidelines could be developed is critically appraised.

Elevated serum enzymes in patients with wasp/bee sting and their clinical significance.

Seventeen patients who had been admitted to hospital for wasp/bee sting were studied. Mild pyrexia was encountered in 7 patients, rash/urticaria in 3, angioneurotic oedema in 2, oliguria in 2, microscopic haematuria and albuminuria in 3, transient hypotension in 1. However, there were frequent elevations of serum glutamic-oxaloacetic transaminase (9 out of 17 patients), serum creatine phosphokinase (14 out of 17 patients) and serum lactate dehydrogenase (8 out of 14 patients), indicating presence of damage to muscle fibres. This was confirmed by the histological findings of a muscle-biopsy from the most severe case. Elevation of serum glutamic-pyruvic transaminase was found in 6, and elevation of serum isocitrate dehydrogenase in 5 out of 14 patients, suggesting presence of liver damage. The above enzyme elevations appeared short-lived except in the clinically most severe patient (case 9) who developed acute tubular necrosis. All patients except the latter suffered no clinical sequelae and there was no correlation between their clinical condition and the presence or degree of elevations of serum enzymes.

Cytokine concentrations in the synovial fluid and plasma of rheumatoid arthritis patients: correlation with bony erosions.

Cytokines are important protein mediators in inflammatory joint diseases. The synovial fluid and plasma concentrations of interleukin-1 alpha (IL-1 alpha), interleukin-2 (IL-2), tumour necrosis factor-alpha (TNF-alpha), interferon-alpha (IF-alpha) and interferon-gamma (IF-gamma) were measured by RIA and ELISA in 28 rheumatoid arthritis (RA) patients (5 males and 23 females). Ten patients with knee effusions due to other causes (osteoarthritis, psoriasis, gout, rheumatic fever, systemic lupus erythematosus) were also studied. Eight of the RA patients had erosive disease. The synovial fluid IL-1 alpha and IL-2 concentrations were higher in Group 1 (erosive) [IL-1 alpha: 524 pg/ml (SEM: 127), IL-2: 3.28 ng/ml (SEM: 1.0)] than in either Group 2 (non-erosive) [IL-1 alpha: 241 pg/ml (SEM: 24), IL-2: 1.93 ng/ml (SEM: 0.6)] or Group 3 (non-RA) [IL-1 alpha: 267 pg/ml (SEM: 58), IL-2: 0.35 ng/ml (SEM: 0.6)] (p < 0.003 and p < 0.06 respectively). Plasma IL-1 and IL-2 levels were higher in Group 1 [IL-1 alpha: 408 pg/ml (SEM: 107), IL-2: 4.20 ng/ml (SEM: 1.5)] than in Group 2 [IL-1 alpha 150 pg/ml (SEM: 15), IL-2: 2.58 ng/ml (SEM: 0.7)] or Group 3 [IL-1 alpha: 140 pg/ml (SEM: 11), IL-2: 1.93 ng/ml (SEM: 0.3)] (p < 0.01, p < 0.009 respectively). There were no differences in the IFN-alpha, IFN-gamma or TNF-alpha levels between groups. These findings suggest that plasma cytokines levels may reflect synovial levels and that IL-1 alpha may play a significant role in erosive joint disease.

Lupus nephritis: correlation between light, electron microscopic and immunofluorescent findings and renal function.

Percutaneous renal biopsies from 56 patients with systemic lupus erythematosus were studied to determine the relationship between renal function and the light microscopic, electron microscopic and immunofluorescent antibody findings. The glomerular lesions were classified into 5 major groups: diffuse membranoproliferative glomerulonephritis (34%), diffuse proliferative glomerulonephritis (26.8%), membranous nephropathy (12.5%), minimal lesion ('nil') and minimal lesion with increased mesangial matrix and/or cells (21.4%) and focal and segmental glomerulonephritis (5.3%). Minimal lesions and focal and segmental glomerulonephritis were invariably associated with normal renal function. Patients with moderate to severe renal involvement and the nephrotic syndrome had predominantly diffuse membranoproliferative and diffuse proliferative glomerulonephritis. Membranous nephropathy was associated with moderate renal involvement and the nephrotic syndrome in 50% of cases. Patients with pure mesangial electron dense deposits had normal renal function or mild renal involvement when the deposits were heavy. Moderate and heavy subepithelial, and intramembranous/subepithelial deposits were associated with moderate to severe renal involvement and the nephrotic syndrome. Renal involvement was most severe with heavy subendothelial deposits. Cytoplasmic tubuloreticular structures measuring approximately 18 to 20 nm in diameter and 80 to 100 nm in length were found in 93% of all biopsies, but bore no relationship to the renal function of the patients. Anti-Hu-IgG fluorescent deposits were found in all the renal biopsies; in 81.3% these were associated with less heavily stained deposits of immunoglobulin IgA, IgD and IgM. Early complement components Clq and C4 were utilized in the complement pathway of activation. Pure mesangial fluorescent deposits were associated with normal renal function or mild proteinuria. Diffuse granular and lumpy deposits along the capillary loops were usually associated with moderate to severe renal involvement and the nephrotic syndrome. In the present series of cases, there was a good correlation between renal function of patients with systemic lupus erythematosus and the glomerular lesions as determined by light, electron microscopic and immunofluorescent microscopic findings.

Henoch-Schoenlein syndrome: a clinical and morphological study of renal biopsies.

Twenty-four patients, 12 children and 12 adults, with the Henoch-Schoenlein syndrome had their renal biopsy specimens studied by light and electron microscopic and immunofluorescent antibody techniques. The principal glomerular lesion was a focal and segmental proliferative glomerulonephritis in 15, a diffuse proliferative glomerulonephritis in 6 and a animal or minor change lesion with mesangial hypertrophy in 3 cases. The proliferation of the cells was mainly mesangial. Renal biopsies taken earlier in the course of the disease showed a greater number with a focal lesion. Electron dense deposits with cellular proliferation and increased matrix were seen in the mesangium. Less frequent subendothelial and occasional subepithelial deposits were found. Capillary loop changes were seen more frequently in the later stages of the disease. Heavy deposits of IgA were found in the mesangium in all cases, and less intense deposits of IgG in 60%. beta 1 C globulin and fibrinogen were found in 80% and IgD and IgM less frequently. Complement activation was via the alternate pathway as early complement components C1q and C4 were absent. Overt allergies, streptococal infections and the HBsAg could not explain the pathogenesis of the disease. Henoch-Schoenlein syndrome is a chronic disease of the mesangium; only 5 patients showed complete recovery, 15 had persistent microscopic hematuria and 3 died or developed renal insufficiency within 8 years. The prognosis was worst with diffuse proliferative glomerulonephritis, widespread focal glomerulonephritis or epithelial cresents formation.

Gout.

Gout is a common disease in the primary health care setting. Diagnosis of primary gout is definite if urate crystals are present in synovial fluid or tophi. The colchicine therapeutic trial is a useful diagnostic aid but not specific. Secondary gout is associated with myeloproliferative disease. Non-steroidal anti-inflammatory agents or colchicine are the main stays of treatment in acute gouty arthritis. In the inter-critical period, uricosuric agents or allopurinol can be used to control hyperuricaemia. Allopurinol is the treatment of choice in secondary gout. Asymptomatic hyperuricaemia is not an indication for therapy.

Bone mineral density measurements using the Hologic QD2000 in 175 Singaporean women aged 20-80.

AIMS: The first aim is to obtain a reference database of bone mineral density (BMD) measurements for Singaporean women across different age groups and to compare this with an American database using the same machine. The second is to study the lifestyle factors that may influence bone mass in these women. METHODS: Subjects were recruited from hospital staff and their relatives. They needed to fulfil inclusion criteria and those with confounding factors such as being on hormone replacement therapy (HRT) were excluded. A lifestyle questionnaire was administered. RESULTS: Across every five-year age band, the mean BMD measurements of the Singaporean women were 3%-8% lower than their American counterparts at the AP spine and 6%-11% lower at the femoral neck. 40.6% either drank milk, ate cheese or took calcium supplements everyday. 16.6% did some form of weight bearing exercise at least once a week. CONCLUSION: A local reference database is needed for the accurate interpretation of BMD measurements as there is significant variation compared to Caucasian values.

Renal arteriovenous fistula following kidney biopsy in systemic lupus erythematosus.

Patients with lupus nephritis frequently undergo renal biopsies. A rare complication of this procedure is the development of renal arteriovenous fistulas. We report two patients with systemic lupus erythematosus (SLE) who developed this vascular complication several years after renal biopsy.

Methylprednisolone in systemic lupus erythematosus.

39 patients who received pulse methylprednisolone for disease manifestations of systemic lupus erythematosus were studied for zero to twenty-four weeks following therapy. Pulse methylprednisolone was given as intravenous infusions of methylprednisolone (10 mg/kg body weight) over one hour each day for three consecutive days. 27 (69.2%) patients were treated for lupus nephritis, 12 (30.8%) patients for non-renal manifestations of lupus. 17 (63.0%) of the renal lupus patients and 7 (58.3%) of the non-renal lupus patients showed clinical response. 11 (28.2%) patients had infections from which 7 (63.6%) died. Overall, 15 (38.5%) patients died. Early deaths (occurring within the first two weeks) were mainly due to disease activity while later deaths were mainly due to infection. In conclusion, the majority of lupus patients appeared to have had a beneficial response to pulse methylprednisolone therapy.

Mortality patterns in a medical intensive care unit.

We studied the mortality rate and patterns in a 6-bedded Medical Intensive Care Unit in a busy general hospital. We found a high mortality rate (26% in-ICU and 42% in-hospitalization) and that mortality was strongly associated with the following factors: cardiac arrest, respirator support, duration of stay in ICU, infection and the immunocompromised state. Lack of formal patient selection and entry criteria and Critical-Care Specialists may be contributing factors.

Infections in systemic lupus erythematosus.

A prospective study was carried out on the occurrence of infections in 28 hospitalised systemic lupus erythematosus (SLE) patients. In 38 episodes of infections, 23 were bacterial (60.5%), 4 were viral (10.6%) and culture negative infections were present in 10 (26.3%). The most common isolated organisms were Staphylococcus aureus (30.4%), Salmonella species (21.7%), Pseudomonas species (13.0%), and Klebsiella species (13.0%). The care rate was 94.7%. Death occurred in 2 patients. Lupus activity, impaired renal function, and cytotoxic therapy did not predispose to infection.

Clinical efficacy of sulbactam/ampicillin in the treatment of moderately severe bacterial infections.

20 patients with moderately severe bacterial infections were studied to determine the clinical efficacy and safety of parenteral sulbactam/ampicillin. There were 9 female and 11 male patients. Their mean age was 51 years. 8 patients had pneumonia, 5 urinary tract infection, 4 cellulitis of the leg and 3 had pustular tonsillitis. 85% of patients had resolution of fever and symptoms within 48 hours of commencing treatment. 95% had successful treatment outcome. The organisms isolated included E. Coli, Klebsiella sp, Branhamella catarrhalis and Bacillus species. In 2 patients, the organisms isolated demonstrated in-vitro ampicillin resistance. However, they recovered fully with sulbactam/ampicillin therapy. No adverse side-effects were reported and dosage adjustment was not required in the elderly.

Absence of retroviral antibodies in the sera of patients with systemic lupus erythematosus.

Retroviruses have been postulated as environmental triggers in the aetiopathogenesis of systemic lupus erythematosus. Sera from 100 lupus patients were screened for the presence of antibodies against recombinant HIV-1 core and envelope, and HIV-2 envelope antigens by an enzyme immunoassay. This will detect antibodies resulting from direct HIV-1 or HIV-2 infections or those generated as a result of antigenic similarities by other human retroviruses. The sera were obtained from 11 male and 89 female lupus patients. Retroviral antibodies were not detected in the sera of these lupus patients, thus contradicting published findings that up to 30% of lupus patients have antibodies against the p24 gag protein of HIV-1.