Publications by authors named "Ling Ho"

50 Publications

Gantry-based 5-fraction Elective Nodal Irradiation in Unfavorable-Risk Prostate Cancer: Outcomes from 2 Prospective Studies comparing SABR Boost with MR Dose Painted HDR Brachytherapy Boost.

Int J Radiat Oncol Biol Phys 2021 Oct 9. Epub 2021 Oct 9.

Odette Cancer Centre, Sunnybrook Health Sciences Centre; Department of Radiation Oncology, University of Toronto; Institute of Health Policy, Management and Evaluation. Electronic address:

Background: ASCO/CCO guidelines recommend brachytherapy boost for intermediate-risk (IR) or high-risk (HR) prostate cancer (PCa) patients. Stereotactic ablative body radiotherapy (SABR) is an emerging technique for PCa but its use in HR disease is limited. We compare efficacy, toxicity, and quality-of-life (QoL) in patients treated on 2 prospective protocols that used SABR boost or MR-guided HDR brachytherapy boost (MR-HDR) with 6-18 months of androgen deprivation therapy (ADT).

Methods: In XXXXXX study (study 1), patients received 40Gy to prostate and 25Gy to pelvis in 5 weekly fractions. In XXXXXX (study 2), patients received HDR-BT 15Gy x 1 to the prostate and ≤22.5Gy to the MRI nodule, followed by 25Gy in 5 weekly fractions to pelvis. All patients received between 6 and 18 months of androgen deprivation therapy.

Results: Thirty patients (NCCN 7% unfavorable IR, and 93% HR) completed study 1 while 31 patients (NCCN 3% favorable IR, 47% Unfavorable IR and 50% HR) completed treatment as per study 2. Median follow-up was 72 and 62 months, respectively. In study 2, 6 patients had BF and all 6 developed metastatic disease. Actuarial 5-year BF was 0% for study 1 and 18.2% for study 2 (p=0.005). There was no significant difference in worst acute or late GI or GU toxicity. Grade 3 late GU toxicity was noted in 3% of the patients in study 2 (HDR-BT boost). There was no significant difference in QoL or minimally clinical important change.

Conclusions: In the context of 5-fraction pelvic radiotherapy and ADT, there does not appear to be a significant difference in toxicity or QoL between SABR vs. HDR BT boost. While efficacy favored the SABR boost cohort, this should be viewed in the context of limitations and biases associated with comparing two sequential phase II studies.
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http://dx.doi.org/10.1016/j.ijrobp.2021.10.003DOI Listing
October 2021

Elective nodal ultra hypofractionated radiation for prostate cancer: Safety and efficacy from four prospective clinical trials.

Radiother Oncol 2021 Sep 4;163:159-164. Epub 2021 Sep 4.

Odette Cancer Centre, Sunnybrook Health Sciences Centre, Canada; Department of Radiation Oncology, University of Toronto, Canada; Institute of Health Policy, Management and Evaluation, Canada. Electronic address:

Background And Purpose: The role of elective nodal irradiation (ENI) in localized prostate cancer (PCa) is controversial. With increasing use of SBRT to the prostate, data is needed regarding the safety and efficacy of ENI using ultra-hypofractionated radiation (UHRT).

Materials And Methods: Between 2013-2020, 4 prospective clinical trials of intermediate or high-risk PCa receiving dose-escalated RT to the prostate (via HDR brachytherapy or SBRT boost) and ENI using UHRT (25 Gy in 5 weekly fractions) were conducted. Primary endpoints included acute genitourinary and gastrointestinal toxicities (CTCAE v3.0/4.0), and secondary endpoints included late genitourinary and gastrointestinal toxicities, patient-reported quality of life (EPIC) and biochemical failure (Phoenix definition).

Results: One-hundred sixty-five patients were enrolled, of whom 98 (59%) had high-risk disease. ADT was used in 141 (85%). Median follow-up was 38 months (IQR 10-63). The worst acute genitourinary and gastrointestinal toxicities respectively were 48% and 7.5% for grade 2, and 2.7% and 0% for grade 3. Cumulative incidence of late grade 2+ genitourinary and gastrointestinal toxicities at 36 months were 58% and 11.3% and for late grade 3+ toxicities were 1% and 0%, respectively. No grade 4+ acute or late toxicities were observed. Bowel and sexual toxicity significantly worsened up to 1-year compared to baseline. Over time, urinary (p < 0.0001), bowel (p = 0.0018) and sexual (p < 0.0001) scores significantly improved. The 3-year biochemical recurrence-free survival was 98%.

Conclusion: ENI using UHRT is associated with low incidence of grade 3+ toxicity, while grade 1-2 acute genitourinary and gastrointestinal toxicity is common. Randomized phase 3 trials are needed.
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http://dx.doi.org/10.1016/j.radonc.2021.08.017DOI Listing
September 2021

Antiviral Therapy for Varicella Zoster Virus (VZV) and Herpes Simplex Virus (HSV)-Induced Anterior Uveitis: A Systematic Review and Meta-Analysis.

Front Med (Lausanne) 2021 2;8:686427. Epub 2021 Jul 2.

Advanced Eye Centre, Post-Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

Herpes simplex virus (HSV) and varicella zoster virus (VZV) are the most common ocular pathogens associated with infectious anterior uveitis. Currently, there are a number of antiviral agents administered to treat viral anterior uveitis (VAU). However, there is no consensus or guidelines about the most appropriate approach leading for the best treatment outcomes with fewer ocular complications. To perform a systematic review and meta-analysis of the efficacy of different antiviral therapies in the management of anterior uveitis secondary to HSV and VZV. We searched PubMed, Web of Science, CINAHL, OVID, and Embase up to January 2020. Randomized trials, non-randomized intervention studies, controlled before and after studies and observational studies assessing the effect of oral and or topical treatments for VAU were considered. Data extraction and analysis with evaluation of the risk of bias in the included trials were performed. Oral acyclovir demonstrated a statistically significant good treatment outcome in the management of VZV anterior uveitis (vs. placebo) (OR 0.26, 95% CI 0.11-0.59), but did not have similar effect in HSV anterior uveitis (OR 0.47, 95% CI 0.15-1.50). In the treatment of VZV anterior uveitis, there was significant superiority of oral acyclovir-7 day course-over topical acyclovir (OR 4.17, 95% CI 1.28-13.52). Whereas, there was no significant superiority of one of the following treatment regimens over the others: topical acyclovir over topical corticosteroids (OR 1.86, 95% CI 0.67-5.17), and oral acyclovir-7 day course-over oral acyclovir-14 day course-(OR 0.21, 95% CI 0.01-4.50) or oral valaciclovir (OR 1.40, 95% CI 0.48-4.07). Treatment of HSV and VZV anterior uveitis is currently based on individual experiences and limited literature, largely due to weak clinical trial evidence in this regard. Our results highlight the existence of a substantial gap in our evidence base. This finding might contribute to future research studies to ascertain the role of different antiviral therapies in the treatment of VAU. PROSPERO registration number: CRD420202 00404.
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http://dx.doi.org/10.3389/fmed.2021.686427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284188PMC
July 2021

Stereotactic pelvic radiotherapy with HDR boost for dose escalation in intermediate and high-risk prostate cancer (SPARE): Efficacy, toxicity and quality of life.

Radiother Oncol 2021 08 3;161:40-46. Epub 2021 Jun 3.

Odette Cancer Centre, Sunnybrook Health Sciences Centre, Canada; Department of Radiation Oncology, University of Toronto, Canada; Institute of Health Policy, Management and Evaluation, Canada. Electronic address:

Background: The ASCO/CCO guidelines recommend brachytherapy (BT) boost for eligible intermediate- (IR) or high-risk (HR) prostate cancer (PCa) patients. We present efficacy, toxicity and quality-of-life (QoL) outcomes in patients treated on a prospective protocol of MRI dose-painted high-dose-rate BT boost (HDR-BT) followed by 5-fraction pelvic radiotherapy (RT) and 6-18 months of androgen deprivation therapy (ADT).

Methods: In this phase I/II study, IR or HR PCa patients received HDR-BT 15 Gy × 1 to prostate and up to 22.5 Gy to MRI nodule, followed by 25 Gy in 5, weekly fractions to pelvis. Toxicity was assessed using CTCAEv3.0, and QoL was captured using EPIC questionnaire. Biochemical failure (BF; nadir + 2.0), and proportion of patients with PSA < 0.4 ng/ml at 4-years (4yPSARR) were evaluated. A minimally clinically important change (MCIC) was recorded if QoL score decreased >0.5 standard deviation of baseline scores.

Results: Thirty-one patients (NCCN 3.2% favorable IR, 48.4% unfavorable IR and 48.4% HR) completed treatment with a median follow-up of 61 months. Median D90 to MR nodule was 19.0 Gy and median prostate V100% was 96.5%. The actuarial 5-year BF rate was 18.2%, and the 4yPSARR was 71%. One patient died of PCa. Acute grade 2 and 3 toxicities: GU: 50%, 7%, and GI: 3%, none, respectively. Late grade 2 and 3 toxicities were: GU: 23%, 3%, and GI: 7%, none, respectively. Proportion of patients with MCIC was 7.7% for urinary domain and 32.0% for bowel domain.

Conclusions: This novel treatment protocol incorporating MRI dose-painted HDR-BT boost and 5-fraction pelvic RT with ADT is well tolerated.
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http://dx.doi.org/10.1016/j.radonc.2021.05.024DOI Listing
August 2021

Dietary Factors and Sleep Quality Among Hemodialysis Patients in Malaysia.

J Ren Nutr 2021 Apr 7. Epub 2021 Apr 7.

Department of Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Seri Kembangan, Selangor, Malaysia; Research Centre of Excellence, Nutrition and Non-communicable Diseases, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Seri Kembangan, Selangor, Malaysia.

Objectives: Poor sleep quality is a commonly seen problem in hemodialysis patients. This study investigated the associations between dietary factors and sleep quality among hemodialysis patients.

Design And Methods: This is a cross-sectional study conducted among 184 eligible hemodialysis patients at four dialysis units in Malaysia. Three days dietary recall were used in the analysis of dietary intake and behavior. Sleep quality was assessed through Pittsburgh Sleep Quality Index.

Results: More than half of the patients were poor sleepers. Among the sleep components, sleep latency affected patients the most, with the use of sleep medications was relatively low. A majority of the patients had inadequate dietary intake of energy (88%) and protein (75%). Dietary protein, potassium adjusted for body weight, and sodium intake were significantly increased in poor sleepers. Lower percentage of energy from carbohydrates; higher percentage of energy from fats; higher intakes of dietary protein, fat, phosphorus, and sodium were correlated with poorer sleep quality and its components. Skipping dinner on non-dialysis days and having supper on dialysis days were associated with poor sleep quality.

Conclusion: Poor sleep is prevalent among hemodialysis patients. Sleep quality of hemodialysis patients was highly associated with certain dietary factors. Periodical assessment of sleep quality and dietary intake is necessary to identify poor sleepers with inappropriate dietary intake to allow effective clinical and nutritional interventions to improve the sleep quality and nutritional status of these patients.
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http://dx.doi.org/10.1053/j.jrn.2021.02.003DOI Listing
April 2021

Denosumab versus alendronate in long-term glucocorticoid users: A 12-month randomized controlled trial.

Bone 2021 05 23;146:115902. Epub 2021 Feb 23.

Department of Nuclear Medicine, Tuen Mun Hospital, Hong Kong.

Objectives: To compare the efficacy of denosumab and alendronate on raising spine bone mineral density (BMD) in long-term glucocorticoid (GC) users.

Methods: Adult patients receiving long-term prednisolone (≥2.5 mg/day for ≥1 year) were recruited and randomized to either subcutaneous denosumab (60 mg/6 months) or oral alendronate (70 mg/week). BMD (lumbar spine, femoral neck, hip) and bone markers (serum P1NP and CTX) were measured at month 0, 6 and 12. The difference in spine BMD (primary outcome) at month 12 was compared between the two groups.

Results: 139 subjects were recruited (age 50.0 ± 12.7 years; 96% women): 69 assigned denosumab and 70 assigned alendronate. At entry, 73(53%) patients were osteoporotic and 82(59%) patients were naive to the bisphosphonates. Baseline clinical characteristics and BMD values were similar in the two groups. At month 12, a significant gain in mean BMD at the lumbar spine (+3.5 ± 2.5%; p<0.001), hip (+0.9 ± 2.8%; p=0.01) and femoral neck (+1.04 ± 4.1%; p=0.047); was observed in denosumab-treated patients, whereas the corresponding change was +2.5 ± 2.9% (p<0.001), +1.6 ± 2.7% (p<0.001) and + 1.5 ± 3.9% (p=0.002) in the alendronate group. The spine, but not the hip or femoral neck, BMD at month 12 was significantly higher in the denosumab than alendronate group after adjustment for baseline BMD values, age, sex, osteoporosis risk factors and the cumulative prednisolone doses received in one year. The drop in P1NP and CTX was significantly higher in the denosumab than alendronate group. Frequency of adverse events (AEs), including infections, was similar in the two treatment arms. Seven patients withdrew from the study but not related to AEs.

Conclusions: In patients receiving long-term GCs, denosumab is superior to alendronate in raising the spine BMD after 12 months. Both drugs are well-tolerated.
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http://dx.doi.org/10.1016/j.bone.2021.115902DOI Listing
May 2021

Quantitating Interfraction Target Dynamics During Concurrent Chemoradiation for Glioblastoma: A Prospective Serial Imaging Study.

Int J Radiat Oncol Biol Phys 2021 03 14;109(3):736-746. Epub 2020 Oct 14.

Department of Radiation Oncology, Sunnybrook Odette Cancer Centre, Toronto, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Canada. Electronic address:

Purpose: Magnetic resonance image (MRI) guided radiation therapy has the potential to improve outcomes for glioblastoma by adapting to tumor changes during radiation therapy. This study quantifies interfraction dynamics (tumor size, position, and geometry) based on sequential magnetic resonance imaging scans obtained during standard 6-week chemoradiation.

Methods And Materials: Sixty-one patients were prospectively imaged with gadolinium-enhanced T1 (T1c) and T2/FLAIR axial sequences at planning (Fx0), fraction 10 (Fx10), fraction 20 (Fx20), and 1 month after the final fraction of chemoradiation therapy (P1M). Gross tumor volumes (GTVs) and clinical target volumes (CTVs) were contoured at all time points. Target dynamics were quantified by absolute volume (V), volume relative to Fx0 (V), and the migration distance (d; the linear displacement of the GTV or CTV relative to Fx0). Temporal changes were assessed using a linear mixed-effects model.

Results: Median volumes at Fx0, Fx10, Fx20, and P1M for the GTV were 18.4 cm (range, 1.1-110.5 cm), 14.7 cm (range, 0.9-115.1 cm), 13.7 cm (range, 0.6-174.2 cm), and 13.0 cm (range, 0.9-76.3 cm), respectively, with corresponding median V of 0.88 at Fx10, 0.77 at Fx20, and 0.71 at P1M relative to Fx0 (P < .001 for all). The GTV (CTV) migration distances were greater than 5 mm in 46% (54%) of patients at Fx10, 50% (58%) of patients at Fx20, and 52% (57%) of patients at P1M. Dynamic tumor morphologic changes were observed, with 40% of patients exhibiting a decreased GTV (V ≤1) with a d >5 mm during chemoradiation therapy.

Conclusions: Clinically meaningful tumor dynamics were observed during chemoradiation therapy for glioblastoma, supporting evaluation of daily MRI guided radiation therapy and treatment plan adaptation.
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http://dx.doi.org/10.1016/j.ijrobp.2020.10.002DOI Listing
March 2021

Trend of Survival of a Cohort of Chinese Patients With Systemic Lupus Erythematosus Over 25 Years.

Front Med (Lausanne) 2020 11;7:552. Epub 2020 Sep 11.

Department of Medicine, Tuen Mun Hospital, Hong Kong, China.

To revisit the trend of survival of systemic lupus erythematosus in a cohort of Chinese patients over 25 years. Patients who fulfilled the 1997 ACR criteria for SLE and were followed in our hospital since 1995 were included. Patients were stratified into two groups according to the year of diagnosis: (1) 1995-2004 and (2) 2005-2018. Survival of patients was studied by Kaplan-Meier analysis. Organ damage as assessed by the Systemic Lupus International Collaborating Clinics (SLICC) damage index (SDI) and causes of death in the first 10 years of SLE onset was compared between the two groups. Cox regression was used to study factors associated with survival. A total of 1,098 SLE patients were registered in our database. After excluding 157 patients diagnosed outside the time period of 1995-2018, 941 patients were studied (92% women). All were ethnic Chinese. The mean age of SLE onset was 35.1 ± 14.4 years, and the mean duration of observation was 13.1 ± 6.6 years. Seventy-seven (8.2%) patients were lost to follow-up. Groups 1 and 2 consisted of 364 and 577 patients, respectively. The mean SDI score at 10 years of disease onset was significantly higher in group 1 than group 2 patients (1.01 ± 1.43 vs. 0.57 ± 0.94; < 0.01), particularly in the neuropsychiatric, musculoskeletal, and gonadal domains. Within 10 years of SLE onset, 32 (8.8%) patients in group 1 and 25 (4.3%) patients in group 2 died ( = 0.005). The 5- and 10-year cumulative survival rates were 93.6 and 91.0% in group 1 and 96.5 and 94.2% in group 2 patients, respectively (log-rank test = 0.048). Infection accounted for more than half of the deaths in both groups. More group 1 than group 2 patients died of vascular events, but the difference was not statistically significant. Cox regression showed that the age of SLE onset and damage score accrued at 10 years, but not the time period in which SLE was diagnosed, were significantly associated with mortality. The improvement in survival of our SLE patients is probably related to the accrual of less organ damage in the past 15 years.
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http://dx.doi.org/10.3389/fmed.2020.00552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516076PMC
September 2020

Long-term outcome of a randomised controlled trial comparing tacrolimus with mycophenolate mofetil as induction therapy for active lupus nephritis.

Ann Rheum Dis 2020 08 24;79(8):1070-1076. Epub 2020 May 24.

Medicine, United Christian Hospital, Hong Kong, Hong Kong.

Objectives: To report the 10-year outcome of lupus nephritis (LN) treated with mycophenolate mofetil (MMF) or tacrolimus (TAC) induction in a randomised controlled trial.

Methods: Patients with active LN were treated with MMF or TAC combined with high-dose prednisolone. Responders were switched to azathioprine (AZA) at month 6. Clinical outcomes at 10 years (renal flares, renal function decline and mortality) were assessed. Factors affecting prognosis were studied by Cox regression. Urine protein-to-creatinine ratio (uPCr) and estimated glomerular filtration rate (eGFR) at different time points were evaluated for their prediction of a poor prognosis by receiver operating characteristic (ROC) analysis.

Results: 150 patients were studied (age 35.5±12.8 years). Complete renal response rate was similar between MMF (59%) and TAC-treated patients (62%; p=0.71). AZA maintenance was given to 79% patients. After 118.2±42 months, proteinuric and nephritic renal flares occurred in 34% and 37% of the MMF, and 53% and 30% of the TAC groups of patients, respectively (p=0.49). The cumulative incidence of a composite outcome of ↓eGFR ≥30%, chronic kidney disease stage 4/5 or death at 10 years was 33% in both groups (p=0.90). Factors independently associated with a poor renal prognosis were first-time LN (HR 0.12 (0.031 to 0.39); p=0.01), eGFR (HR 0.98 (0.96 to 0.99); p=0.008) and no response at month 6 (HR 5.18 (1.40 to 19.1); p=0.01). ROC analysis revealed an uPCr >0.75 and eGFR of <80 mL/min at month 18 best predicted a poor renal prognosis.

Conclusions: Long-term data confirmed non-inferiority of TAC to MMF as induction therapy of LN. An uPCr≤0.75 and eGFR of ≥80 mL/min at month 18 best predicted a favourable 10-year outcome and may be suitable targets for induction/consolidation therapy.

Trial Registration Number: NCT00371319.
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http://dx.doi.org/10.1136/annrheumdis-2020-217178DOI Listing
August 2020

Prevalence and risk factors of herpes zoster infection in patients with biopsy proven lupus nephritis undergoing immunosuppressive therapies.

Lupus 2020 Jul 14;29(8):836-844. Epub 2020 May 14.

Division of Rheumatology, Department of Medicine, Tuen Mun Hospital, Hong Kong, SAR China.

Objectives: To study the prevalence of herpes zoster infection in patients with biopsy-confirmed lupus nephritis undergoing immunosuppressive therapies.

Methods: Patients who had histologically active lupus nephritis between 2004 and 2018 were retrospectively reviewed. Clinical and laboratory data at baseline and six months post-therapy were collected. The incidence of herpes zoster reactivation within two years of lupus nephritis treatment was calculated. Risk factors for herpes zoster reactivation were studied by logistic regression.

Results: Patients ( = 251) with 311 episodes of lupus nephritis were studied (92% women; age 34.2 ± 14.2 years; histological classes III/IV ± V (69%)). Within two years of therapy, 55 (18%) episodes of lupus nephritis were complicated by herpes zoster infection (incidence 8.84/100 patient-years). Fourteen episodes (25%) of herpes zoster were treated by intravenous anti-viral drugs in hospital but disseminated disease or mortality was not reported. Significant post-herpetic neuralgia developed in 9% of the episodes. Patients with herpes zoster reactivation, compared with those without, were more likely to have first-time renal disease and a shorter systemic lupus erythematosus duration at lupus nephritis than those without. Disease activity, treatment response and other clinical/laboratory parameters were not significantly different between patients with and without herpes zoster reactivation. Herpes zoster-infected patients had been treated with a significantly higher dose of prednisolone as induction therapy. Logistic regression revealed that first-time renal disease, peak daily mycophenolate mofetil dose and cumulative cyclophosphamide dose during induction therapy were significantly associated with herpes zoster reactivation.

Conclusions: Herpes zoster reactivation is common in lupus nephritis patients but unpredictable from clinical parameters. Although adverse outcomes of herpes zoster infection are uncommon, using the minimally effective doses of mycophenolate mofetil and cyclophosphamide during induction therapy may help reduce the risk of herpes zoster infection.
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http://dx.doi.org/10.1177/0961203320923739DOI Listing
July 2020

Evaluating the Tolerability of a Simultaneous Focal Boost to the Gross Tumor in Prostate SABR: A Toxicity and Quality-of-Life Comparison of Two Prospective Trials.

Int J Radiat Oncol Biol Phys 2020 05 25;107(1):136-142. Epub 2020 Jan 25.

Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Purpose: Dose-escalated stereotactic ablative radiotherapy (SABR) to the whole prostate may be associated with better outcomes but has a risk of increased toxicity. An alternative approach is to focally boost the dominant intraprostatic lesion (DIL) seen on magnetic resonance imaging. We report the toxicity and quality-of-life (QOL) outcomes of 2 phase 2 trials of prostate and pelvic SABR, with or without a simultaneous DIL boost.

Methods And Materials: The first trial treated patients with high-risk prostate cancer to a dose of 40 Gy to the prostate and 25 Gy to the pelvis in 5 fractions. The second trial treated patients with intermediate-risk and high-risk prostate cancer to a dose of 35 Gy to the prostate, 25 Gy to the pelvis, and a DIL boost up to 50 Gy in 5 fractions. Acute toxicities, late toxicities, and QOL were assessed.

Results: Thirty patients were enrolled in each trial. In the focal boost cohort, the median DIL D90% was 48.3 Gy. There was no significant difference in acute grade ≥2 gastrointestinal or genitourinary toxicity between the 2 trials or in cumulative worst late gastrointestinal or genitourinary toxicity up to 24 months. There was no significant difference in QOL domain scores or minimally clinical important change between the 2 trials.

Conclusions: Prostate and pelvic SABR with a simultaneous DIL boost was feasible. Acute grade ≥2 toxicity, late toxicity, and QOL seemed to be comparable to a cohort that did not receive a focal boost. Further follow-up will be required to assess long-term outcomes, and randomized data are required to confirm these findings.
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http://dx.doi.org/10.1016/j.ijrobp.2019.12.044DOI Listing
May 2020

Dosimetric predictors of toxicity and quality of life following prostate stereotactic ablative radiotherapy.

Radiother Oncol 2020 03 3;144:135-140. Epub 2019 Dec 3.

Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Canada; Institute of Health Policy Management and Evaluation, University of Toronto, Canada. Electronic address:

Purpose: SABR offers an effective treatment option for clinically localized prostate cancer. Here we report the dosimetric predictors of late toxicity and quality of life (QOL) in a pooled cohort of patients from four phase II trials.

Methods: The combined cohort included all three prostate cancer risk groups. The prescription dose was 35-40 Gy in 5 fractions. Toxicity (CTCAE) and QOL (EPIC) were collected. Multiple dosimetric parameters for the bladder, rectum and penile bulb were collected. Univariate (UVA) followed by multivariate (MVA) logistic regression analysis was conducted to search for significant dosimetric predictors of late GI/GU toxicity, or minimal clinically important change in the relevant QOL domain.

Results: 258 patients were included with median follow up of 6.1 years. For QOL, bladder Dmax, V38, D1cc, D2cc, D5cc and rectal V35 were predictors of urinary and bowel MCIC on UVA. On MVA, only bladder V38 remained significant. For late toxicity, various parameters were significant on UVA but only rectal Dmax, V38 and bladder D2cc were significant predictors on MVA.

Conclusions: This report confirms that the high-dose regions in the bladder and rectum are more significant predictors of late toxicity and QOL after prostate SABR compared to low-dose regions. Caution must be taken to avoid high doses and hotspots in those organs.
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http://dx.doi.org/10.1016/j.radonc.2019.11.017DOI Listing
March 2020

Safety and immune response of a live-attenuated herpes zoster vaccine in patients with systemic lupus erythematosus: a randomised placebo-controlled trial.

Ann Rheum Dis 2019 12 17;78(12):1663-1668. Epub 2019 Sep 17.

Department of Microbiology, University of Hong Kong, Hong Kong, SAR China.

Objectives: To study the safety and immunogenicity of a live-attenuated herpes zoster (HZ) vaccine in patients with systemic lupus erythematosus (SLE).

Methods: Adult SLE patients having a SLEDAI <6 and stable immunosuppressive treatment for ≥6 months were recruited. Participants were randomly assigned to receive HZ vaccine (Zostavax) or placebo injection. Anti-varicella zoster virus (VZV) IgG reactivity (baseline and week 6) was measured by an enzyme-linked fluorescence assay. Cell-mediated response was assessed by a VZV-stimulated interferon-gamma (IFN-γ) enzyme-linked ELISPOT assay. Adverse events and immune responses of the two groups were compared.

Results: 90 SLE patients were recruited (age 45.6±14.1 years; 93% women) and assigned to Zostavax or placebo (in 1:1 ratio). Baseline clinical parameters were similar between the two groups. The change in anti-VZV IgG from week 0 to 6 was +59.8% in the vaccine and -2.1% in the placebo group. Week 6 anti-VZV IgG was significantly higher in vaccinated than placebo-treated patients, after adjustment for baseline (4.16±1.26 vs 3.32±1.01; p<0.001). The number of IFN-γ secreting T-cell spots decreased in the placebo-treated patients (-17%) but increased in vaccinated patients (+42%). The T-cell spots number at week 6 was significantly higher in vaccine-than placebo-treated patients after adjustment for baseline (38.1±78.2 vs 23.1±47.9; p=0.02). Significantly more vaccinated patients reported self-limiting injection site reaction than controls (31% vs 7%; p<0.01). Two vaccinated patients (4.4%) and one (2.2%) placebo-treated patient had mild/moderate SLE flares but no patients developed HZ eruption within 6 weeks postvaccination.

Conclusions: In patients with stable SLE not receiving intensive immunosuppression, Zostavax was well-tolerated and provoked an immune response.

Trial Registration Number: US ClinicalTrials.gov registry (NCT02477150).
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http://dx.doi.org/10.1136/annrheumdis-2019-215925DOI Listing
December 2019

SABR in High-Risk Prostate Cancer: Outcomes From 2 Prospective Clinical Trials With and Without Elective Nodal Irradiation.

Int J Radiat Oncol Biol Phys 2019 05 14;104(1):36-41. Epub 2018 Nov 14.

Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Canada; Department of Health Policy, Measurement and Evaluation, University of Toronto, Toronto, Canada. Electronic address:

Purpose: There is limited data on stereotactic ablative radiation therapy (SABR) in high-risk prostate cancer (PCa), especially regarding the role of elective nodal irradiation (ENI). This study compares 2 prospective phase 2 trials using SABR in high-risk PCa, with and without ENI.

Methods And Materials: Patients had high-risk PCa. Those in trial 1 received 40 Gy in 5 fractions to the prostate and 30 Gy in 5 fractions to the seminal vesicles. Patients in trial 2 received 40 Gy in 5 fractions to the prostate and 25 Gy in 5 fractions to the pelvis and seminal vesicles. National Cancer Institute Common Terminology Criteria for Adverse Events toxicities were collected. Biochemical failure (BF) was defined as nadir + 2, and the 4-year prostate-specific antigen (PSA) response rate (4yPSARR) was <0.4 ng/mL.

Results: Sixty patients were included (trial 1, n = 30; trial 2, n = 30). Median follow-up was 5.6 years and 4.0 years. The median nadir PSA was 0.02 ng/mL for both trials. Six patients had BF, all from trial 1. The BF rate was 14.6% at 5 years in trial 1 and 0% in trial 2. Sixty-three percent of patients in trial 1 and 93% in trial 2 had a 4yPSARR. Two patients died in trial 1, 1 from metastatic disease. One patient in trial 2 died of other causes. No other patients developed metastatic disease, and 1 patient in trial 1 had castrate resistant PCa. Overall survival at 5 years was 93.2% and 96.7% (P = .86). There was significantly worse late gastrointestinal and sexual toxicity in trial 1, but there was no difference in late genitourinary toxicity.

Conclusions: SABR in high-risk PCa yields biochemical control rates that may be comparable to that of other radiation therapy modalities. ENI using SABR is feasible and may lead to a significant improvement in biochemical control and in 4yPSARR, without an increase in late gastrointestinal or genitourinary toxicity. Longer follow-up would provide a better assessment of biochemical control. Well-conducted phase 3 trials are needed to fully establish the role of SABR and ENI in high-risk PCa.
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http://dx.doi.org/10.1016/j.ijrobp.2018.11.011DOI Listing
May 2019

Ocular Autoimmune Systemic Inflammatory Infectious Study (OASIS) - Report 2: Pattern of Uveitis Investigations in Singapore.

Ocul Immunol Inflamm 2020 18;28(1):92-99. Epub 2018 Oct 18.

Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.

: To analyze the pattern of laboratory investigations of uveitis at a tertiary referral eye care center in Singapore.: Retrospective analysis of 2040 uveitis cases from the Ocular Autoimmune Systemic Inflammatory Infectious Study (OASIS) database over a 12-year period (2004 - 2015).: Patients with retinal vasculitis (RV) had the most tests utilized per patient (6.79), followed by intermediate uveitis (IU) (5.25), panuveitis (Pan) (5.12), posterior uveitis (PU) (4.17), anterior uveitis (AU) (2.75), and keratouveitis (KU) (1.10). The most frequently utilized test for infective etiology were the VDRL (41.3%), Syphilis IgG (29.5%), and T-SPOT.TB (24.6%). For autoimmune tests, ANA was most utilized (18.2%), followed by anti-dsDNA (14.8%), and HLA-B27 (12.4%).: There was high utilization of autoimmune tests such as ANA, anti-dsDNA, RF, and ANCA, despite its limited yield. Rationalization of investigations in patients with ocular inflammation via a stepladder approach may help optimize the use of limited resources.
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http://dx.doi.org/10.1080/09273948.2018.1535080DOI Listing
December 2020

Analysis of 130 Cases of Sympathetic Ophthalmia - A Retrospective Multicenter Case Series.

Ocul Immunol Inflamm 2019 12;27(8):1259-1266. Epub 2018 Sep 12.

Department of Ophthalmology, National Healthcare Group Eye Institute, Singapore.

To analyze the demographic profile, treatment, and visual outcome of the patients with sympathetic ophthalmia (SO) in a multicenter collaborative retrospective cohort study. Medical records of the patients with SO from UK, Singapore, India were reviewed for history of ocular trauma or surgery and subsequent development of uveitis consistent with SO, presenting symptoms, treatment, and visual outcomes. A total of 130 patients were diagnosed with SO during the study period. Eighty-one (62.3%) patients were men. The mean age was 48.4 ± 15.5 years. The most common presenting symptom was blurring of vision (89.2%), followed by pain (29.2%) and floaters (23.8%). Ninety-two (70.7%) required additional immunosuppressive therapy. Thirty-six (27.9%) patients underwent enucleation of the inciting eye. SO is a potentially sight-threatening disease with high rates of visual loss. It warrants prompt evaluation and treatment. With the advances and availability in immunotherapy, the visual prognosis is relatively good.
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http://dx.doi.org/10.1080/09273948.2018.1517894DOI Listing
May 2020

The Collaborative Ocular Tuberculosis Study (COTS)-1: A Multinational Description of the Spectrum of Choroidal Involvement in 245 Patients with Tubercular Uveitis.

Ocul Immunol Inflamm 2018 Aug 29:1-11. Epub 2018 Aug 29.

aa Laura Bassi Centre of Expertise Ocuvac, Center for Pathophysiology, Immunology and Infectiology , Medical University of Vienna , Vienna, Austria.

Purpose: To contribute a global description of the spectrum of choroidal involvement in tubercular uveitis (TBU).

Methods: Retrospective cohort study of TBU patients with choroidal involvement from 25 centers between January 2004 and December 2014. Medical records of patients with a minimum follow-up of 1 year were reviewed.

Results: 245 patients were included. The phenotypic variations included serpiginous-like choroiditis (SLC) (46%), tuberculoma (13.5%), multifocal choroiditis (MFC) (9.4%), ampiginous choroiditis (9%), among others. 219 patients were treated with anti-tubercular therapy (ATT) (n = 219/245, 89.38%), 229 patients with steroids (n = 229/245, 93.47%) and 28 patients with immunosuppressive agents (n = 28/245, 11.42%). Treatment failure was noted in 38 patients (n = 38/245, 15.5%). Patients with SLC and ampiginous choroiditis appeared to have superior outcomes on survival analysis (p = 0.06).

Conclusion: This study provides a comprehensive description of choroidal involvement in TBU. Patients with SLC and ampiginous choroiditis may have better clinical outcomes.
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http://dx.doi.org/10.1080/09273948.2018.1489061DOI Listing
August 2018

Phase 1-2 Study of Stereotactic Ablative Radiotherapy Including Regional Lymph Node Irradiation in Patients With High-Risk Prostate Cancer (SATURN): Early Toxicity and Quality of Life.

Int J Radiat Oncol Biol Phys 2018 12 31;102(5):1438-1447. Epub 2018 Jul 31.

Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada; Department of Health Policy, Measurement and Evaluation, University of Toronto, Toronto, Canada. Electronic address:

Purpose: Five-fraction stereotactic ablative radiation therapy appears to be gaining popularity in treatment of prostate cancer, but it has not been extensively tested in the context of pelvic radiation. The objective of this prospective prostate and pelvic SABR study is to report the acute toxicity, late toxicity, and quality of life (QoL) after study completion.

Methods And Materials: A phase 1/2 study was conducted for patients with high-risk prostate cancer. Radiation therapy was planned to deliver 25 Gy to pelvis and seminal vesicles (SV) and a simultaneous integrated boost (SIB) of up to 40 Gy to the prostate in 5 fractions, weekly, over 29 days. Androgen deprivation therapy was used for 12 to 18 months. Common Terminology Criteria for Adverse Events version 3.0 was used to assess worst acute and late toxicities. QoL data was captured using the Expanded Prostate Cancer Index Composite questionnaire (EPIC).

Results: Thirty patients completed the planned treatment with a median follow-up of 25.7 months (range, 18.5-30.7 months). The following "worst" acute and late toxicities were observed: grade 2 genitourinary toxicity, 46.7% and 52%, respectively; grade 2 gastrointestinal toxicity, 3.3% and 32%, respectively. No grade 3 or higher toxicities were noted. Mean (95% confidence interval) EPIC urinary QoL scores were 86.6 (81.9-91.3), 87.1 (81.4-92.6), and 87.9 (80.1-95.7) at baseline, 3 months and 24 months; bowel scores were 94.1 (91.3-97.0), 93.2 (89.1-97.2), and 92.4 (87.7- 97.1), respectively.

Conclusions: This gantry-based novel fractionation schedule incorporating pelvic radiation for high-risk prostate cancer in combination with androgen deprivation therapy is feasible and well tolerated.
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http://dx.doi.org/10.1016/j.ijrobp.2018.07.2005DOI Listing
December 2018

Serum 25-hydroxyvitamin D3 levels and flares of systemic lupus erythematosus: a longitudinal cohort analysis.

Clin Rheumatol 2018 Oct 16;37(10):2685-2692. Epub 2018 Jul 16.

Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.

The aim of this study is to evaluate the relationship between baseline serum 25-hydroxyvitamin D3 levels and SLE activity/flares over time. This is a longitudinal study of 276 patients who fulfilled ≥ 4 ACR criteria for SLE and recruited in the year 2011. Serum samples were collected at baseline and assayed for 25-hydroxyvitamin D3 at the end of a mean follow-up of 32.5 months. Participants were stratified into three groups according to baseline 25-hydroxyvitamin D3 levels: group I (< 15 ng/ml, deficiency), group II (15-30 ng/ml, insufficiency), and group III (> 30 ng/ml, adequate). Baseline and summated SLE disease activity index (SLEDAI) score over time and the annual incidence of lupus flares were compared among these groups. 25-hydroxyvitamin D3 levels of < 15, 15-30, and > 30 ng/ml were present in 26, 54, and 20% of the recruited patients, respectively. Group I had significantly higher baseline SLEDAI scores. After a follow-up of 32.5 ± 5.5 months, 153 mild/moderate and 91 severe flares developed. The mean summated SLEDAI was 3.2 ± 2.0 in group I, 2.4 ± 1.9 in group II and 2.7 ± 2.1 in group III patients (P = 0.02). The annual incidence of mild/moderate and severe flares was 0.26 ± 0.39 and 0.20 ± 0.45 (group I); 0.20 ± 0.33 and 0.09 ± 0.22 (group II); and 0.20 ± 0.32 and 0.14 ± 0.46 (group III), respectively (P > 0.05). In a subgroup of 73 patients who were clinically and serologically quiescent at baseline, a similar trend of more flares was observed in group I patients. Vitamin D deficiency was frequent in Chinese SLE patients and was associated with more active disease at baseline and over time, as well as a trend of more severe lupus flares.
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http://dx.doi.org/10.1007/s10067-018-4204-1DOI Listing
October 2018

Clinical Features of Scleritis Across the Asia-Pacific Region.

Ocul Immunol Inflamm 2019 28;27(6):920-926. Epub 2018 Jun 28.

Ophthalmology Department, Save Sight Institute, Sydney Medical School, University of Sydney , Sydney , Australia.

: To examine the spectrum of scleritis in four tertiary institutions across the Asia-Pacific. : Clinical records from 354 patients were reviewed from centers in Australia, Singapore, and India, excluding those with insufficient data ( = 24). : Indian patients presented younger (41.5 ± 13.4 years) than Australians (50.8 ± 17.5) and Singaporeans (48.6 ± 15.9), with fewer women (49% vs 62%/57%). Diffuse disease was universally most common. Autoimmune and infectious disease proportions were similar in Australia (31%/10.3%) and Singapore (27.5%/8.3%) but reversed in India (8.3%/30%). Necrotizing scleritis was most frequently associated with infection (27.3%). Presumed ocular tuberculosis accounted for 75% of infectious cases in India. Posterior scleritis had the highest complication rate (82.4%) and immunosuppressants used per patient (0.98 ± 0.31 95% CI). : Clinical presentations of scleritis vary across the Asia-Pacific, particularly in endemic regions for tuberculosis such as India, where it affects younger men with a predominance of nodular and infectious disease.
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http://dx.doi.org/10.1080/09273948.2018.1484496DOI Listing
February 2020

Urinary angiostatin, CXCL4 and VCAM-1 as biomarkers of lupus nephritis.

Arthritis Res Ther 2018 01 11;20(1). Epub 2018 Jan 11.

Department of Biomedical Engineering, Houston, TX, USA.

Background: The aim was to study urinary angiostatin, CXC chemokine ligand 4 (CXCL4) and vascular cell adhesion molecule-1 (VCAM-1) as biomarkers of renal disease in systemic lupus erythematosus (SLE).

Method: Patients who fulfilled ≥ 4 American College of Rheumatology (ACR) criteria for SLE with active renal, active non-renal or inactive disease, and a group of healthy controls were studied. Urine samples were assayed for angiostatin, CXCL4 and VCAM-1 by ELISA, and normalized by creatinine. Receiver operating characteristic analysis was performed to obtain the best cutoff values to calculate the performance of these markers in differentiating the different groups of patients as compared to anti-double-stranded DNA (anti-dsDNA) and complement C3. Correlation between these urinary biomarkers and various renal parameters was also tested.

Results: Patients with SLE (n = 227; 80 with inactive SLE, 67 with active non-renal disease and 80 with active renal disease; 94% women; age 39.2 ± 13.8 years) and 53 controls (96% women) were studied. All were ethnic Chinese. Urinary angiostatin, CXCL4 and VCAM-1 (normalized for creatinine) were significantly higher in patients with active renal disease than in patients with active non-renal disease, patients with inactive SLE and controls. These markers correlated significantly with total SLE disease activity index (SLEDAI) and renal SLEDAI scores, and with the urinary protein-to-creatinine ratio. Urine angiostatin exhibited higher specificity and sensitivity in differentiating active renal from active non-renal SLE (area under the curve (AUC) 0.87) than serum anti-dsDNA/C3. Urine CXCL4 (AUC 0.64) and VCAM-1 (AUC 0.73), on the other hand, performed similarly to anti-dsDNA/C3. All three markers performed comparably to anti-dsDNA/C3 in distinguishing active from inactive SLE. In a subgroup of 68 patients with paired renal biopsy, the urinary levels of these proteins did not differ significantly between the proliferative and non-proliferative types of lupus nephritis. Urinary CXCL4 and VCAM-1 correlated significantly with the histologic activity score, and urinary angiostatin correlated significantly with proteinuria in this subgroup.

Conclusions: Urinary angiostatin, CXCL4 and VCAM-1 are potential biomarkers for SLE, in particular lupus nephritis. Further longitudinal studies are necessary to delineate the performance of these markers in predicting renal flares and prognosis in SLE patients.
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http://dx.doi.org/10.1186/s13075-017-1498-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5765646PMC
January 2018

The Collaborative Ocular Tuberculosis Study (COTS)-1 Report 3: Polymerase Chain Reaction in the Diagnosis and Management of Tubercular Uveitis: Global Trends.

Ocul Immunol Inflamm 2019 20;27(3):465-473. Epub 2017 Dec 20.

ab Laura Bassi Centre of Expertise Ocuvac, Center for Pathophysiology, Immunology and Infectiology , Medical University of Vienna , Vienna , Austria.

: To analyze the role of polymerase chain reaction (PCR) of ocular fluids in management of tubercular (TB) anterior, intermediate, posterior, and panuveitis. In Collaborative Ocular Tuberculosis Study (COTS)-1 (25 centers,  = 962), patients with TB-related uveitis were included. 59 patients undergoing PCR of intraocular fluids (18 females; 53 Asian Indians) were included. 59 (6.13%) of COTS-1 underwent PCR analysis. PCR was positive for Mycobacterium TB in 33 patients (23 males; all Asian Indians). 26 patients were PCR negative (18 males). Eight patients with negative PCR had systemic TB. Anti-TB therapy was given in 18 negative and 31 PCR cases. At 1-year follow-up, five patients with positive PCR (15.15%) and three with negative PCR (11.54%) had persistence/worsening of inflammation. : Data from COTS-1 suggest that PCR is not commonly done for diagnosing intraocular TB and positive/negative results may not influence management or treatment outcomes in the real world scenario.
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http://dx.doi.org/10.1080/09273948.2017.1406529DOI Listing
December 2019

Effect of the metabolic syndrome on organ damage and mortality in patients with systemic lupus erythematosus: a longitudinal analysis.

Clin Exp Rheumatol 2018 May-Jun;36(3):389-395. Epub 2017 Oct 18.

Department of Medicine, Tuen Mun Hospital, Hong Kong, SAR China.

Objectives: To study the effect of the metabolic syndrome (MetS) on organ damage and mortality in patients with SLE.

Methods: Consecutive patients who fulfilled ≥4 ACR criteria for SLE were assessed for the MetS in October 2010. The MetS was defined by the updated joint consensus criteria, using the Asian criteria for central obesity. Longitudinal data on organ damage and mortality were retrieved. The association between MetS and new damage and mortality was studied by logistic regression.

Results: A total of 577 SLE patients were followed (93% women; age 41.2±13.4 years; SLE duration 9.3±7.2 years) and 85 (14.7%) patients qualified the MetS. After a follow-up of 66.3±1.8 month, new organ damage and vascular events developed in 128(22%) and 23(4.0%) patients, respectively. Thirty-nine (6.8%) patients succumbed. Patients with the MetS, compared to those without, had significantly more SLICC damage score accrual (0.70±1.0 vs 0.26±0.6; p<0.001), new vascular events (11% vs 2.8%; p=0.001), all-cause (14% vs 5.5%; p=0.003) and vascular (7.1% vs 0.2%; p<0.001) mortality. Logistic regression revealed that the MetS was significantly associated with new damage in the renal (OR 5.48[2.06-14.6]; p=0.001) and endocrine system (OR 38.0[4.50-321]; p=0.001), adjusted for age, sex, SLE duration, ever smoking, antiphospholipid antibodies and the new use of glucocorticoids or hydroxychloroquine since recruitment. Moreover, the presence of the MetS also significantly increased the risk of new vascular events (OR 3.38[1.31-8.74];p=0.01) and vascular mortality (OR 28.3[3.24-247]; p=0.002) after adjustment for the same covariates.

Conclusion: In this longitudinal study, the MetS is significantly associated with new organ damage, vascular events and mortality in patients with SLE.
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July 2018

Ocular Toxoplasmosis in Tropical Areas: Analysis and Outcome of 190 Patients from a Multicenter Collaborative Study.

Ocul Immunol Inflamm 2018 11;26(8):1289-1296. Epub 2017 Oct 11.

a National Healthcare Group Eye Institute , Tan Tock Seng Hospital , Singapore , Singapore.

Purpose: To describe clinical findings and outcomes for ocular toxoplasmosis in an international multicenter collaborative study.

Methods: Retrospective analysis of 190 patients diagnosed with ocular toxoplasmosis from three study sites (Brazil, India, and Singapore).

Results: There were 93 (48.9%) females with a mean age of 32.8 years. The most common symptoms were isolated blurring of vision (36.8%), followed by blurring of vision with floaters (21.1%). Treatment regimens varied largely from monotherapy to multiple combination therapies. Final visual acuity of ≥20/40 was achieved in 106 (74.2%) patients. In a median follow-up period of 31 weeks (range 12-749 weeks), 83/190 (43.7%) patients suffered a relapse.

Conclusions: There appears to be geographical variation in the presentation of ocular toxoplasmosis. Compared to previous studies, we did not observe the '"dual peak" phenomenon of chronic and active disease based on age at presentation, and there was less bilateral and macular involvement (but more peripheral involvement).
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http://dx.doi.org/10.1080/09273948.2017.1367407DOI Listing
December 2018

Prevalence of remission and its effect on damage and quality of life in Chinese patients with systemic lupus erythematosus.

Ann Rheum Dis 2017 Aug 21;76(8):1420-1425. Epub 2017 Apr 21.

Department of Medicine, Tuen Mun Hospital, Hong Kong, China.

Objectives: To study the prevalence of remission and its effect on damage and quality of life (QOL) in Chinese patients with systemic lupus erythematosus (SLE).

Methods: Patients who fulfilled ≥4 American College of Rheumatology criteria for SLE were identified. Their remission status at last clinic visits was determined by the European consensus criteria (complete/clinical remission ± immunosuppressive drugs). The increase in SLE damage index (SDI) in the preceding 5 years was compared between patients who were and were not in remission for ≥5 years. QOL of patients as assessed by the validated Chinese version of the Medical Outcomes Study Short-Form-36 (SF36) and the LupusPRO was also compared between the remission and non-remission groups by statistical analysis.

Results: 769 SLE patients were studied (92% women; age: 46.4±14.6 years; SLE duration: 12.6±8.1 years). At last visit, clinical remission was present in 259 (33.7%) patients and complete remission was present in 280 (36.4%) patients. Clinical and complete remissions for ≥5 years were achieved in 64 (8.3%) and 129 (16.8%) of the patients, respectively. Patients remitted for ≥5 years were older, and had significantly lower prevalence of renal involvement, leucopenia or thrombocytopaenia. Fifty-three (6.9%) patients in remission ≥5 years were taken off all medications, including hydroxychloroquine (HCQ) (drug-free). Patients who remitted for ≥5 years but off-therapy (except HCQ) had significantly less SDI increment than those who did not remit (0.17±0.53 vs 0.67±1.10; p<0.001). Among 453 patients who had QOL assessment, remission for ≥5 years was associated with significantly higher SF36 and the total health-related scores of the LupusPRO.

Conclusions: Durable remission can be achieved in a quarter of patients with SLE. Patients with remission for ≥5 years have significantly less damage accrual and better QOL. Prolonged remission is an appropriate criterion for outcome assessment in SLE.
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http://dx.doi.org/10.1136/annrheumdis-2016-210382DOI Listing
August 2017

Ocular Autoimmune Systemic Inflammatory Infectious Study (OASIS)-report 4: analysis and outcome of scleritis in an East Asian population.

J Ophthalmic Inflamm Infect 2017 Dec 15;7(1). Epub 2017 Feb 15.

National Healthcare Group Eye Institute, Tan Tock Seng Hospital, Singapore, 308433, Singapore.

Background: The purpose of this study is to evaluate the spectrum of scleritis from database of Ocular Autoimmune Systemic Inflammatory Infectious Study (OASIS) at a tertiary eye referral eye institute in Singapore. Clinical records of 120 patients with scleritis from a database of 2200 patients from Ocular Autoimmune Systemic Inflammatory Infectious Study (OASIS) were reviewed.

Results: 56.6% were females, with a mean age of 48.6 ± 15.9 years. 75 (62.5%) had diffuse anterior scleritis, 25 (20.8%) had nodular anterior scleritis, 7 (5.8%) had necrotizing anterior scleritis and 13 (10.8%) had posterior scleritis. Ocular complications were observed in 53.3% of patients, including anterior uveitis (42.5%), raised intraocular pressure (12.5%), and corneal involvement (11.7%). Autoimmune causes were associated with 31 (25.8%) of patients, and 10 (8.3%) patients had an associated infective etiology, much higher than Caucasian studies. 53.3% of patients were treated with oral corticosteroids while 26.7% required immunosuppressives.

Conclusions: Infective etiology needs to be considered in patients of scleritis from Asian origin. In our study and in OASIS database, scleritis was associated with systemic autoimmune disease and ocular complications.
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http://dx.doi.org/10.1186/s12348-017-0124-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5311008PMC
December 2017

Association of depressive/anxiety symptoms with quality of life and work ability in patients with systemic lupus erythematosus.

Clin Exp Rheumatol 2016 May-Jun;34(3):389-95. Epub 2016 Mar 25.

Division of Rheumatology, Department of Medicine, Tuen Mun Hospital, Hong Kong, China.

Objectives: To study the association of depressive/anxiety symptoms with health-related quality of life (HRQoL) and work ability in Chinese patients with systemic lupus erythematosus (SLE).

Methods: Consecutive patients with ≥4 ACR criteria for SLE were recruited. Depressive and anxiety symptoms were assessed by the Hospital Anxiety and Depression scale (HADS). HRQoL was assessed by the Chinese version of MOS-Short Form (SF)-36. Disease activity of SLE was assessed by the SLE disease activity index (SLEDAI) and organ damage was assessed by the ACR/SLICC damage index (SDI). The relationship between HAD scores, work ability and HRQoL was studied.

Results: A total of 367 SLE patients were studied (95% women; age 40.2±12.9 years; disease duration 9.3±7.2 years). Fifty-five (15%) patients had HADS-depression score ≥10 and 70 (19%) patients had HADS-anxiety score ≥10. Patients with either score ≥10 had significantly lower SF36 score (physical and mental component) than those with score <10. In separate linear regression models, the mental and physical component scores of SF36 were significantly associated with the HAD-depression and HAD-anxiety score after adjustment for age, sex, SLE duration, years of education, religious belief, marital status, employment status, poverty, SDI and mean SLEDAI score in the preceding year. Among those who were working in the preceding year (n=190), 30(16%) patients either quitted their job (n=22) or reduced working hours (n=8). Patients with work disability had significantly higher HAD-depression score than those without (6.31±5.51 vs 3.93±3.72; p=0.03).

Conclusions: Depressive/anxiety symptoms were fairly common in SLE patients and independently associated with poorer HRQoL. Patients with more depressive symptoms were more likely to experience work disability.
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August 2016

Plant genetic transformation efficiency of selected Malaysian rice based on selectable marker gene (hptII).

Pak J Biol Sci 2014 Apr;17(4):472-81

Rice is one of the most important cereal crops with great potential for biotechnology progress. In transformation method, antibiotic resistance genes are routinely used as powerful markers for selecting transformed cells from surrounding non-transformed cells. In this study, the toxicity level of hygromycin was optimized for two selected mutant rice lines, MR219 line 4 and line 9. The mature embryos were isolated and cultured on an MS medium with different hygromycin concentrations (0, 20, 40, 60, 80 and 100 mg L(-1)). Evidently, above 60 mg L(-1) was effective for callus formation and observed completely dead. Further there were tested for specific concentration (0-60). Although, 21.28% calli survived on the medium containing 45 mg L(-1) hygromycin, it seemed suitable for the identification of putative transformants. These findings indicated that a system for rice transformation in a relatively high frequency and the transgenes are stably expressed in the transgenic plants. Green shoots were regenerated from the explant under hygromycin stress. RT-PCR using hptII and gus sequence specific primer and Southern blot analysis were used to confirm the presence of the transgene and to determine the transformation efficiency for their stable integration in regenerated plants. This study demonstrated that the hygromycin resistance can be used as an effective marker for rice transformation.
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http://dx.doi.org/10.3923/pjbs.2014.472.481DOI Listing
April 2014

Switching of oral bisphosphonates to denosumab in chronic glucocorticoid users: a 12-month randomized controlled trial.

Bone 2015 Jun 8;75:222-8. Epub 2015 Mar 8.

Department of Nuclear Medicine, Tuen Mun Hospital, Hong Kong.

Objectives: To evaluate the effect of switching from oral bisphosphonates to denosumab on bone mineral density (BMD) in long-term glucocorticoid users.

Methods: Adult patients who were receiving long-term prednisolone (≥2.5 mg/day for ≥1 year) and oral bisphosphonates (≥2 years) were recruited. Participants were randomized to either continue oral bisphosphonates or switch to denosumab (60 mg subcutaneously every 6 months) for 12 months. Serial BMD (lumbar spine, hip) and bone turnover markers (serum osteocalcin, P1NP, β-CTX) were measured.

Results: 42 women were recruited (age 54.7±12.9 years; 21 shifted to denosumab and 21 continued on bisphosphonates). The duration of prednisolone therapy was 101±66.3 months and the daily dose was 4.4±2.1 mg. Baseline demographic data, osteoporosis risk factors, and BMD at various sites were similar between the two groups of patients. At month 12, BMD of the spine and hip increased by +3.4±0.9% (p=0.002) and +1.4±0.6% (p=0.03), respectively, in the denosumab group; whereas the corresponding change was +1.5±0.4% (p=0.001) and +0.80±0.5% (p=0.12) in the bisphosphonate group. The spinal BMD at month 12 was significantly higher in the denosumab than bisphosphonate group after adjustment for baseline BMD and β-CTX values, and other confounding factors (p=0.01). Bone turnover markers (β-CTX and P1NP) were more strongly suppressed by denosumab than the bisphosphonates. Minor infections were more common in denosumab-treated patients while other adverse events occurred at similar frequencies between the two groups.

Conclusions: In patients receiving long-term glucocorticoids, switching from oral bisphosphonates to denosumab resulted in greater gain of the spinal BMD and suppression of bone turnover markers after 12 months of therapy. The results have to be confirmed by a larger clinical trial with fracture as endpoint.
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http://dx.doi.org/10.1016/j.bone.2015.03.002DOI Listing
June 2015

Illegitimacy and sibship assignments in oil palm (Elaeis guineensis Jacq.) half-sib families using single locus DNA microsatellite markers.

Mol Biol Rep 2015 May 16;42(5):917-25. Epub 2014 Nov 16.

Department of Field Crops, Faculty of Agricultural Sciences, University of Sulaimani, Sulaimani, Iraqi Kurdistan Region,

Oil palm breeding has been progressing very well in Southeast Asia, especially in Malaysia and Indonesia. Despite this progress, there are still problems due to the difficulty of controlled crossing in oil palm. Contaminated/illegitimate progeny has appeared in some breeding programs; late and failure of detection by the traditional method causes a waste of time and labor. The use of molecular markers improves the integrity of breeding programs in perennial crops such as oil palm. Four half-sib families with a total of 200 progeny were used in this study. Thirty polymorphic single locus DNA microsatellites markers were typed to identify the illegitimate individuals and to obtain the correct parental and progeny assignments by using the CERVUS and COLONY programs. Three illegitimate palms (1.5%) were found, and 16 loci proved to be sufficient for sibship assignments without parental genotypes by using the COLONY program. The pairwise-likelihood score (PLS) method was better for half-sib family assignments than the full likelihood (FL) method.
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http://dx.doi.org/10.1007/s11033-014-3829-7DOI Listing
May 2015
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