Therapeutic applications of germline testing for cancer predisposition genes in Asia in the real world.

BACKGROUND: Germline genetic testing is traditionally carried out in patients suspected with hereditary cancer syndrome for enhanced cancer surveillance and/or preventive strategies, but is increasingly carried out for therapeutic indications. MATERIALS AND METHODS: We conducted a retrospective review of patients who underwent germline genetic testing at our centre to determine the prevalence of actionable pathogenic germline variants (PGV) and their clinical utility. RESULTS: From 2000 to 2022, 1154 cancer patients underwent germline testing, with the majority (945/1154) tested with multi-gene panels. Four hundred and eleven (35.6%) patients harboured a PGV and 334 (81%) were clinically actionable. BRCA1/2 accounted for 62.3% of actionable mutations, followed by mismatch repair (18%), and other homologous recombination repair (HRR) genes (19.7%). One hundred and fifty-two germline-positive patients have advanced cancers, and 79 received germline-directed therapies (poly ADP ribose polymerase inhibitors = 75; immunotherapy = 4). Median duration of immunotherapy and poly ADP ribose polymerase were 20.5 months (range 5-40 months) and 8 months (range 1-76 months), respectively. Among BRCA/HRR mutation carriers who received platinum-based chemotherapy, pathological complete response rate in the neoadjuvant setting was 53% (n = 17 breast cancers) and objective response rate was >80% in the advanced setting (n = 71). CONCLUSIONS: One-third of cancer patients tested carried a PGV and ∼80% were clinically actionable. Three-quarters of germline-positive advanced cancer patients received germline-directed therapies in the real world, underscoring the practical utility of germline testing to guide cancer therapeutics.

Back-translating GWAS findings to animal models reveals a role for Hgfac and Slc39a8 in alcohol and nicotine consumption.

Alcohol and tobacco are the most commonly used addictive substances, with high comorbidity rates between alcohol use disorder and tobacco use disorder. Risk for alcohol and nicotine addiction is highly heritable, and they share common genetic factors. A GWAS in over 1 million individuals has revealed 566 genetic variants in 406 loci associated with multiple stages of alcohol and tobacco use. Three novel genes-SLC39A8, GRK4 and HGFAC-within loci associated with altered alcoholic drinks per week (ADW) or cigarettes per day (CPD) were selected to further study their role in alcohol and tobacco use disorder. The role of these genes was assessed using the two-bottle choice addiction paradigm in transgenic mice for each of the genes. We found significant decreases in chronic alcohol consumption and preference in female Hgfac knockout (KO) mice, and decreased nicotine preference in male Hgfac KO compared with wild-type (WT) mice. Additionally, male Slc39a8 hypomorph mice showed greater overall nicotine preference compared with WT mice, while no differences were detected for Grk4 KO mice in alcohol or nicotine consumption and preference in either sex. Thus, this study implicates Hgfac and Slc39a8 in alcohol and tobacco use in a sex-specific manner.

Flavor-specific enhancement of electronic cigarette liquid consumption and preference in mice.

BACKGROUND: The use of electronic cigarettes has increased over the past decade. To determine how the abuse liability of electronic cigarette liquids (e-liquids) differs from nicotine alone, and to determine the impact of flavor, we compared nicotine-containing fruit- and tobacco-flavored e-liquids, and their nicotine-free versions, to nicotine alone in mouse models of oral consumption, reward and aversion. METHODS: Adult male C57BL/6 J mice voluntarily consumed oral nicotine, equivalent nicotine concentrations of fruit- and tobacco-flavored e-liquid, and equivalent dilutions of the nicotine-free versions in 2-bottle choice tests. Conditioned place preference and place aversion were assessed with peripherally administered e-liquids or nicotine. Serum nicotine and cotinine levels were measured after subcutaneous injections of e-liquid or nicotine. RESULTS: Mice showed higher consumption and preference for the fruit-flavored e-liquid compared with nicotine alone. This increase was not due to the flavor itself as consumption of the nicotine-free fruit-flavored e-liquid was not elevated until the highest concentration tested. The increased consumption and preference were not observed with the tobacco-flavored e-liquid. The conditioned place preference, place aversion and nicotine pharmacokinetics of the fruit-flavored e-liquid were not significantly different from nicotine alone. CONCLUSIONS: Our data suggest that fruit, but not tobacco flavor, increased the oral consumption of e-liquid compared with nicotine alone. Moreover, this enhancement was not due to increased consumption of the flavor itself, altered rewarding or aversive properties after peripheral administration, or altered pharmacokinetics. This flavor-specific enhancement suggests that some flavors may lead to higher nicotine intake and increased use of e-liquids compared with nicotine alone.

Ambiguity hindering self-management and prevention of osteoporosis in post-menopausal women.

As osteoporosis relies largely on self-managed prevention and adherence to long-term treatment regimens, it is imperative that those at risk understand the disease that they are attempting to prevent. Ambiguity regarding osteoporosis and reluctance to take anti-osteoporosis medication (AOM) as well as calcium was noted in Australian post-menopausal women. This may lead to underestimating women's own risk of osteoporosis and fracture. INTRODUCTION: Fragility fractures caused by osteoporosis have been known to inflict significant personal and financial burden on individuals and society. As treatment of osteoporosis relies largely on self-managed prevention and adherence to long-term AOM regimens, it is imperative that women have a sound understanding of the disease that they are attempting to prevent. Much can also be gained from qualitatively exploring the level of osteoporosis knowledge particularly in post-menopausal women who are at greater risk of osteoporosis and fractures. This study thus aims to determine what post-menopausal Australian women know about osteoporosis and osteoporosis prevention. METHOD: Six focus group sessions, using purposive sampling, were conducted with 23 female participants (mean age 68 years (range 62-83)). Women responded to a series of open-ended questions regarding their knowledge about osteoporosis. The audiotaped focus groups were transcribed verbatim and analysed using a thematic analysis framework. RESULTS: Three key themes were identified: ambiguity about the nature of osteoporosis, ambiguity about osteoporosis prevention and reluctance to take AOM and calcium. CONCLUSION: Ambiguity associated with risk and prevention may provide women with a false sense of security that they are adequately acting to prevent the disease. Underestimation of their risk of osteoporosis and fracture as well as reluctance associated with AOM may be barriers to osteoporotic fracture prevention.

The Impact of Fracture Incidence on Health Related Quality of Life among Community-Based Postmenopausal Women.

This prospective study aimed to examine the impact of fracture incidence on health-related quality of life (HRQOL) among postmenopausal women. Study subjects were Australian female community-dwellers in the Global Longitudinal Study of Osteoporosis in Women (GLOW). Self-administered questionnaires were collected annually from 2007 to 2010. Outcomes were the Medical Outcomes Study Short Form-36 (SF-36 physical function (SF36PFS) and vitality (SF36VS) scores), European Quality of Life (EQ-5D), and self-reported general health (GH) of excellent/good. Questionnaires were divided into prior to, the 1st, the 2nd, and the 3rd year after incident fracture assessments. Generalized linear models with generalised estimating equations (GEE) were employed for the analysis. The 2,872 participants (age: median 65; interquartile range 60-73 years) provided a total of 10,436 assessments including 266, 165 and 76 assessments for the 1st, the 2nd, and the 3rd year after incident fracture, respectively. Multivariate adjustments showed reductions in HRQOL measures peaking at the 1st year for SF36VS (coefficient -3.0; 95% CI: -5.1, -0.8) and EQ-5D (coefficient -0.03; 95% CI: -0.06, -0.00) and at the 2nd year for SF36PFS (coefficient -3.0; 95% CI: -5.6, -0.5) and GH (odds ratio 0.92; 95% CI: 0.70, 1.19). Fracture incidence reduced HRQOL including vitality and physical function among relatively young, healthy postmenopausal women and the reduction in European Quality of Life measure was clinically important.

Phase I and biomarker study of OPB-51602, a novel signal transducer and activator of transcription (STAT) 3 inhibitor, in patients with refractory solid malignancies.

BACKGROUND: The aim of this study was to determine the maximum-tolerated dose (MTD), safety, pharmacokinetics, and pharmacodynamics of OPB-51602, an oral, direct signal transduction activator of transcription 3 (STAT3) inhibitor, in patients with refractory solid tumors. PATIENTS AND METHODS: Three cohorts were studied: cohort A, a sequential dose escalation of OPB-51602 administered intermittently (days 1-14 every 21 days); cohort B, an expansion cohort evaluating the dose lower than the MTD; cohort C, evaluating continuous daily dosing. RESULTS: Fifty-one patients were studied at 2, 4, and 5 mg per day dosing. The MTD was 5 mg; first-cycle dose-limiting toxicities (DLTs) were grade 3 hyponatremia in one patient, and grade 3 dehydration in another. Intermittent dosing of both 2 and 4 mg doses were tolerable, and the recommended phase II dose was 4 mg. Cohort B investigated 4 mg intermittently, whereas cohort C investigated 4 mg continuously. Common toxicities included fatigue, nausea/vomiting, diarrhea, anorexia, and early-onset peripheral neuropathy. Drug-induced pneumonitis occurred in two patients in cohort C. Continuous dosing was associated with a higher incidence of peripheral neuropathy and a lower mean relative dose intensity, compared with intermittent dosing. Steady-state pharmacokinetics was characterized by high oral clearance, mean elimination half-life ranging from 44 to 61 h, and a large terminal-phase volume of distribution. An active metabolite, OPB-51822, accumulated to a greater extent than OPB-51602. Flow cytometry of peripheral blood mononuclear cells demonstrated pSTAT3 (Tyr(705)) inhibition following exposure. Two patients achieved partial responses at 5 mg intermittently and 4 mg continuously; both had epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC) with prior EGFR tyrosine kinase inhibitor exposure. CONCLUSION: OPB-51602 demonstrates promising antitumor activity, particularly in NSCLC. Its long half-life and poorer tolerability of continuous dosing, compared with intermittent dosing, suggest that less frequent dosing should be explored. CLINICALTRIALSGOV IDENTIFIER: NCT01184807.

Concern and risk perception: effects on osteoprotective behaviour.

This study aimed to determine the effect that level of concern for osteoporosis, as well as self-perceived risk of osteoporosis and fracture, has on supplementation use, seeking medical advice, bone mineral density (BMD) testing, and antiosteoporosis medication (AOM) use. Study subjects were 1,095 female Australian participants of the Global Longitudinal study of Osteoporosis in Women (GLOW) untreated for osteoporosis at baseline. Study outcomes from self-administered questionnaires included calcium and vitamin D supplementation, self-reported seeking of medical advice regarding osteoporosis, BMD testing, and AOM use in the last 12 months at the late assessment. Logistic regression was used in the analysis. Concern significantly increased the likelihood of seeking medical advice and, however, had no significant impact on screening or treatment. Heightened self-perceived risks of osteoporosis and fracture both significantly increased the likelihood of seeking medical advice and BMD testing while elevated self-perceived risk of fracture increased AOM use. Supplementation use was not significantly associated with concern levels and risk perception. Concern and risk perceptions to osteoporosis and fracture were significantly associated with certain bone-protective behaviours. However, the disconnect between perceived osteoporosis risk and AOM use illustrates the need to emphasize the connection between osteoporosis and fracture in future education programs.

Body fat composition impacts the hematologic toxicities and pharmacokinetics of doxorubicin in Asian breast cancer patients.

Body surface area (BSA)-based dosing leads to wide inter-individual variations in drug pharmacokinetics and pharmacodynamics, whereas body composition has been shown to be a more robust determinant of efficacy and toxicity of certain chemotherapeutic agents. We correlated various parameters of body composition with doxorubicin pharmacokinetics and hematologic toxicities in Asian patients with locally advanced or metastatic breast cancer. Our analysis included 84 patients from two studies who received pre- or post-operative single-agent doxorubicin; pharmacokinetic parameters were available for 44 patients. Body composition parameters were derived from CT cross-sectional images and population pharmacokinetic analysis was conducted using mixed-effects modeling. Higher intra-abdominal fat volume and fat ratio (intra-abdominal:total abdominal fat volume) correlated with greater incidence of grade 4 leukopenia on cycle 1 day 15 (mean intra-abdominal fat volume: 97.4 ± 46.5 cm(3) vs 63.4 ± 30.9 cm(3), p = 0.014; mean fat ratio: 0.43 ± 0.11 vs 0.33 ± 0.09, p = 0.012, grade 4 vs grade 0-3 leukopenia). On subset analysis, this relationship was maintained even in underweight patients. Concordantly, there were positive correlations between doxorubicin AUC and intra-abdominal fat volume as well as total abdominal fat volume (r (2) = 0.324 and 0.262, respectively, all p < 0.001). BSA and muscle volume did not predict for doxorubicin pharmacokinetics or toxicities. High-intra-abdominal fat volume but not BSA predicted for greater doxorubicin exposure and hematologic toxicities, suggesting that body composition is superior to BSA in determining doxorubicin pharmacokinetics and pharmacodynamics. Body composition has an emerging role in chemotherapy dose determination.

Concern and risk perception of osteoporosis and fracture among post-menopausal Australian women: results from the Global Longitudinal Study of Osteoporosis in Women (GLOW) cohort.

PURPOSE: The purpose of this study is to identify factors associated with concern and perception of risks of osteoporosis and osteoporotic fractures and determine whether bone mineral density (BMD) testing influenced concern and risk perception. METHODS: Study subjects (n = 1,082, age 55-94 years) were female Australian participants of the Global Longitudinal Study of Osteoporosis in Women (GLOW). Self-administered questionnaires were sent annually from 2007 to 2010. Study outcomes included 'concern about osteoporosis', 'perception of getting osteoporosis' and 'perception of fracture risk' compared to similar aged women. The closest post-BMD testing or baseline questionnaires were used for women with and without BMD testing, respectively. Multinomial logistic regression was used for the analysis. RESULTS: BMD testing, prior fracture after age 45, younger age and lower self-reported general health were significantly associated with being 'very' or 'somewhat concerned' about osteoporosis and having a 'much higher' or 'little higher' risk perception of osteoporosis and fractures. A poorer BMD result was associated with higher concern and higher risk perceptions. The presence of comorbidities, having ≥2 falls in the preceding year and maternal osteoporosis were associated with higher concern. Maternal osteoporosis, presence of comorbidities, weight loss of ≥5 kg in the preceding year and low body mass index were associated with higher perceptions of osteoporosis risk. CONCLUSION: Women's concern and risk perception of osteoporosis and osteoporotic fractures were reasonably well founded. However, increasing age, height loss, smoking and drinking were not associated with concern and perception despite being known osteoporosis risk factors. These factors should be considered in planning for education and awareness raising programmes.

Serial changes in the expression of breast cancer-related proteins in response to neoadjuvant chemotherapy.

BACKGROUND: Tumour expression of cyclooxygenase-2 (COX-2), epidermal growth factor receptor (EGFR), erythroblastic leukaemia viral oncogene homologue-2 (ErbB2), Ki-67 and p53 in breast cancer are associated with poorer outcomes. We investigated in vivo changes of these proteins with neoadjuvant chemotherapy. PATIENTS AND METHODS: Four core biopsies were taken from 100 breast cancer patients at baseline, during and upon completion of neoadjuvant chemotherapy. Immunohistochemical expression of these proteins were evaluated and correlated with clinicopathological features, clinical response and progression-free survival (PFS). RESULTS: There was a statistically significant change from positivity to negativity in COX-2 expression with chemotherapy (P = 0.002), predominantly in clinical responders (P = 0.002). COX-2-positive tumours that remained positive had shorter PFS than those that turned negative. Estrogen receptor (ER)+ and COX-2+ tumours at baseline that remained COX-2+ fared worse than those that became COX-2 negative (PFS 27 versus 52 months, P = 0.002). No significant changes in IHC expression were observed for ER, progesterone receptor, ErbB2, EGFR, p53 or Ki67. CONCLUSIONS: Chemotherapy induced change in COX-2 expression from positivity to negativity predominantly among clinical responders and is associated with longer PFS. Interaction between COX-2 and ER was observed, suggesting that some hormone receptor-positive patients may benefit from combining COX-2 inhibition with hormonal therapy.

Quantitative assessment of lens opacities with anterior segment optical coherence tomography.

AIM: To evaluate the reliability of lens density measurement with anterior segment optical coherence tomography (OCT) and its association with the Lens Opacity Classification System Version III (LOCS III) grading. METHODS: Fifty-five eyes from 55 age-related cataract patients were included. One eye from each subject was selected at random for lens evaluation. After dilation, lens photographs were taken with a slit lamp and graded against the LOCS III standardised condition. Anterior segment OCT imaging was performed on the same eyes with a high-resolution scan. The association between the anterior segment OCT nucleus density measurement and LOCS III nuclear opalescence (NO) and nuclear colour (NC) scores was evaluated with the Spearman correlation coefficient. Anterior segment OCT measurement precision, coefficient of variation (CVw), and intraclass correlation coefficient (ICC) were calculated. RESULTS: The mean NO and NC scores were 3.39 (SD 1.10) and 3.37 (SD 1.27), respectively. Significant correlations were found between anterior segment OCT nuclear density measurements and the LOCS III NO and NC scores (r = 0.77 and 0.60, respectively, both with p<0.001). The precision, CVw and ICC of anterior segment OCT measurement were 2.05 units, 4.55% and 0.98, respectively. CONCLUSION: Anterior segment OCT nucleus density measurement is reliable and correlates with the LOCS III NO and NC scores.

Assessment of American College of Rheumatology quality criteria for rheumatoid arthritis in a pre-quality criteria patient cohort.

OBJECTIVE: To evaluate the American College of Rheumatology (ACR) starter set of quality measures for rheumatoid arthritis (RA) in an actual patient cohort that preceded publication of the quality measures. METHODS: We retrospectively applied the 2006 ACR quality criteria to a prospectively studied cohort of 568 patients with RA treated by 1,932 unique physicians including 255 different rheumatologists between the years 1999 and 2003. Data on performance were obtained from self-report surveys and medical record review within 12 months. RESULTS: At least 1 joint examination was performed in 98% of patients. Patient and physician global assessments were reported for 79% and 74% of patients, respectively. A total of 85% of patients received disease-modifying antirheumatic drugs (DMARDs). DMARD adjustments were made for 50% of patients in whom increasing disease activity was noted at least once and for 64% of patients in whom increasing disease activity was noted during 2 (of 4) 3-month periods within the year. Compared with self-report surveys, medical records substantially underreported performance on quality measures. CONCLUSION: The ACR-endorsed quality measures for RA can be assessed using available data sources. When both self-report and medical record data are used, adherence rates, designed to serve as minimum standards of care, were moderate or high for most measures. Prior to using indicators to compare quality across groups, specific strategies for operationalizing measures and for using accurate data sources to assess adherence to the measures should be defined.

Application of explicit process of care measurement to rheumatoid arthritis: Moving from evidence to practice.

OBJECTIVE: To construct quality measures with measurement validity and meaning for clinicians. METHODS: We conducted a prospective cohort study of rates of change in disease-modifying antirheumatic drug (DMARD) and/or systemic corticosteroid drug or dose for 568 patients with rheumatoid arthritis (RA) across 6,159 clinical encounters within 12 months to examine how changes in clinical specifications change adherence. RESULTS: Rates of DMARD change were sensitive to specifications regarding the intensity of disease activity (severe or moderate), duration of specified disease activity, and length of the observation period. Over 12 months, the proportions of 377 patients with severe disease activity observed for 1-month, 2-month, and 3-month time blocks who had a change in DMARD drug or dose were 36%, 57%, and 74%, respectively. Over 12 months, a change in DMARD drug or dose was observed for 44%, 50%, and 68% of 377 patients with severe disease within 3 months, 6 months, and 12 months, respectively, of the patient meeting criteria for severe disease activity. A change in DMARD drug or dose was observed for 21%, 23%, and 34% of 149 patients with moderate disease activity within 3, 6, and 12 months, respectively, of the patient meeting criteria for moderate disease activity. CONCLUSION: Rates of pharmacologic interventions for patients with moderate and severe RA disease activity vary substantially by intensity and duration of disease activity and by duration of period for observing change. Lack of precision in explicit process criteria could substantially mislead comparisons of quality of care across comparison groups.

The application of a vacuum-ultraviolet Fourier transform spectrometer and synchrotron-radiation source to measurements of bands of NO. VII. The final report.

Photoabsorption measurements of NO bands have been made by vacuum-ultraviolet Fourier transform spectrometry with a resolution of 0.12 cm(-1) in the wavelength region of 166.2-196.2 nm. Accurate line positions are obtained for the delta(upsilon,0) bands with upsilon=2, 3, the epsilon(upsilon,0) bands with upsilon=2, 3, and the beta(upsilon,0) bands with upsilon=10,12,14. Absolute term values are found for the corresponding upper levels C(2,3), D(2,3), and B(10,12,14). Accurate rotational line integrated cross sections have also been obtained for the lines in these bands. Integrated cross sections reported in our earlier papers [J. Chem. Phys. 109, 1751 (1998); 112, 2251 (2000); 115, 3719 (2001); 116, 155 (2002); 117, 10621 (2002); 119, 8373 (2003)] have been revised, and the results reported here comprise the delta(upsilon,0) bands with upsilon=0-3, the epsilon(upsilon,0) bands with upsilon=0-3, the beta(upsilon,0) bands with upsilon=6,7,9-12,14, and the gamma(3,0) band. For each band, the band oscillator strength is obtained from the sum of the line strengths of all rotational lines, and these are compared with other published values.

Combined photodynamic therapy and intravitreal triamcinolone injection for the treatment of subfoveal choroidal neovascularisation in age related macular degeneration: a comparative study.

AIM: To evaluate the outcomes of combined intravitreal triamcinolone (IVTA) and photodynamic therapy (PDT) with verteporfin in the treatment of subfoveal choroidal neovascularisation (CNV) caused by age related macular degeneration (AMD). METHODS: 48 eyes from 48 patients with subfoveal CNV caused by AMD were prospective recruited, with 24 eyes treated with combined PDT with IVTA and compared with a control group of 24 eyes which received PDT monotherapy. In the combined treatment group, IVTA was performed immediately after PDT as an outpatient procedure. The mean number of treatments, mean logMAR best corrected visual acuity (BCVA), mean line of visual acuity changes, and proportion of patients without moderate visual loss at 1 year were compared between the combined and monotherapy groups. RESULTS: At 1 year the logMAR BCVA for the PDT with IVTA group changed from 0.88 to 0.95 (p = 0.32 compared with baseline), whereas the logMAR BCVA for the monotherapy group reduced from 0.74 to 1.09 (p<0.001 compared with baseline). A significantly higher proportion of patients who had PDT with IVTA did not develop moderate visual loss at 1 year compared with the monotherapy group (70.8% and 33.3% respectively, p = 0.009). Eyes which had combined treatment had significantly fewer lines lost compared with monotherapy alone (0.7 and 3.5 lines respectively, p = 0.015). Subgroup analysis showed that PDT with IVTA is effective in preventing visual loss in both predominately classic and occult CNV groups. The mean number of treatments for the combined and monotherapy groups was 1.5 and 1.96 respectively (p = 0.076). CONCLUSIONS: Combined PDT with IVTA appeared more effective statistically at 12 months for stabilisation of vision (<3 logMAR lines change) compared with PDT monotherapy. Further randomised control trials might be justified to conclude the efficacy of PDT with IVTA.

Circulating antibodies to guanosine in systemic lupus erythematosus: correlation with nephritis and polyserositis by acute and longitudinal analyses.

Systemic lupus erythematosus (SLE) is characterized by autoantibodies, including antibodies to the nucleosides of DNA. Guanosine is the most immunogenic nucleoside. In this study serum antiguanosine antibody levels were compared with disease activity, determined by their SLEDI score, in 86 patients with SLE. Sera from these patients were tested, by ELISA, for autoantibodies to guanosine, single-stranded DNA (ssDNA), and double-stranded DNA (dsDNA). Anti-double-stranded DNA levels were also measured by RIA. Resultant values from these assays were correlated with SLE disease activity, and compared with specific features of SLE. The strongest correlation was higher levels of antiguanosine antibodies in patients with active lupus nephritis and polyserositis compared to patients with inactive disease (P < 0.0001). Antiguanosine levels also correlated with arthritis (P < 0.006), CNS lupus (P < 0.005), and hematologic manifestations of SLE (P < 0.002). To test the validity of this association in chronic SLE, serum antiguanosine antibodies were measured in patients with SLE at various phases of disease activity. Twelve patients with SLE had serum samples drawn at active, active-improved, and inactive phases over a 3-7 y period. Differences were significant for serum antiguanosine antibodies in the active group compared to the inactive group (P < 0.05) and the active vs the active-improved group (P < 0.02), unlike those for dsDNA and ssDNA by ELISA or RIA. Antiguanosine antibodies correlated more closely with disease activity in SLE patients in this longitudinal study than either anti-dsDNA or ssDNA antibodies. Thus, antibodies to guanosine correlated as well or better with disease activity than the other anti-DNA antibodies measured and should be considered to contribute to the pathology of SLE, especially lupus nephritis.

Differentiating osteomyelitis from bone infarction in sickle cell disease.

This brief review discusses one possible approach to evaluating the sickle cell patient with bone pain. The major differential diagnoses include osteomyelitis and bone infarction. Based on previous studies, we provide an approach to assessing and treating patients with the possible diagnosis of osteomyelitis. An algorithm has been provided, which emphasizes the importance of the initial history and physical examination. Specific radiographic studies are recommended to aid in making the initial assessment and to determine whether the patient has an infarct or osteomyelitis. Differentiating osteomyelitis from infarction in sickle cell patients remains a challenge for the pediatrician. This algorithm can be used as a guide for physicians who evaluate such patients in the acute care setting.

HELLP-like syndrome associated with hepatic necrosis in a patient with systemic lupus erythematosus.

Hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome is often associated with preeclampsia or hypertension in pregnancy. Pregnancy in patients with systemic lupus erythematosus (SLE) may be complicated by development of a lupus flare with thrombocytopenia, hypertension and renal insufficiency, which may be difficult to distinguish from preeclampsia. We describe a 20-year-old patient with SLE and anticardiolipin antibodies who developed a HELLP-like syndrome during 2 successive pregnancies without the more typical symptoms of preeclampsia or hypertension. This unusual presentation of HELLP syndrome during pregnancy in a patient with SLE was evidenced by hematologic and liver enzyme abnormalities as a sign of ongoing hepatic necrosis. Early recognition of this syndrome is important because it may result in rapid deterioration with progressive hepatic necrosis that can be reversible with early termination of pregnancy.