Objective: Ovarian clear cell carcinoma (OCCC) is associated with chemoresistance. Limited data exists regarding the efficacy of targeted therapies such as immune checkpoint inhibitors (ICI) and bevacizumab, and the role of secondary cytoreductive surgery (SCS). Methods: We retrospectively analyzed genomic features and treatment outcomes of 172 OCCC patients treated at our institution from January 2000 to May 2022. Next-generation sequencing (NGS) was performed where sufficient archival tissue was available. Results: 64.0% of patients were diagnosed at an early stage, and 36.0% at an advanced stage.Patients with advanced/relapsed OCCC who received platinum-based chemotherapy plus bevacizumab followed by maintenance bevacizumab had a median first-line progressionfree survival (PFS) of 12.2 months, compared with 9.3 months for chemotherapy alone (hazard ratio=0.69; 95% confidence interval [CI]=0.33, 1.45). In 27 patients who received an ICI, the overall response rate was 18.5% and median duration of response was 7.4 months (95% CI=6.5, 8.3). In 17 carefully selected patients with fewer than 3 sites of relapse, median PFS was 35 months (95% CI=0, 73.5) and median overall survival was 96.8 months (95% CI=44.6, 149.0) after SCS. NGS on 58 tumors revealed common mutations in ARID1A (48.3%), PIK3CA (46.6%), and KRAS (20.7%). Pathogenic alterations in PIK3CA, FGFR2, and NBN were associated with worse survival outcomes. Median tumor mutational burden was 3.78 (range, 0–16). All 26 patients with available loss of heterozygosity (LOH) scores had LOH <16%. Conclusion Our study demonstrates encouraging outcomes with bevacizumab and ICI, and SCS in select relapsed OCCC patients. Prospective trials are warranted.

Objective: Ovarian clear cell carcinoma (OCCC) is associated with chemoresistance. Limited data exists regarding the efficacy of targeted therapies such as immune checkpoint inhibitors (ICI) and bevacizumab, and the role of secondary cytoreductive surgery (SCS). Methods: We retrospectively analyzed genomic features and treatment outcomes of 172 OCCC patients treated at our institution from January 2000 to May 2022. Next-generation sequencing (NGS) was performed where sufficient archival tissue was available. Results: 64.0% of patients were diagnosed at an early stage, and 36.0% at an advanced stage.Patients with advanced/relapsed OCCC who received platinum-based chemotherapy plus bevacizumab followed by maintenance bevacizumab had a median first-line progressionfree survival (PFS) of 12.2 months, compared with 9.3 months for chemotherapy alone (hazard ratio=0.69; 95% confidence interval [CI]=0.33, 1.45). In 27 patients who received an ICI, the overall response rate was 18.5% and median duration of response was 7.4 months (95% CI=6.5, 8.3). In 17 carefully selected patients with fewer than 3 sites of relapse, median PFS was 35 months (95% CI=0, 73.5) and median overall survival was 96.8 months (95% CI=44.6, 149.0) after SCS. NGS on 58 tumors revealed common mutations in ARID1A (48.3%), PIK3CA (46.6%), and KRAS (20.7%). Pathogenic alterations in PIK3CA, FGFR2, and NBN were associated with worse survival outcomes. Median tumor mutational burden was 3.78 (range, 0–16). All 26 patients with available loss of heterozygosity (LOH) scores had LOH <16%. Conclusion Our study demonstrates encouraging outcomes with bevacizumab and ICI, and SCS in select relapsed OCCC patients. Prospective trials are warranted.

Objective: Ovarian clear cell carcinoma (OCCC) is associated with chemoresistance. Limited data exists regarding the efficacy of targeted therapies such as immune checkpoint inhibitors (ICI) and bevacizumab, and the role of secondary cytoreductive surgery (SCS). Methods: We retrospectively analyzed genomic features and treatment outcomes of 172 OCCC patients treated at our institution from January 2000 to May 2022. Next-generation sequencing (NGS) was performed where sufficient archival tissue was available. Results: 64.0% of patients were diagnosed at an early stage, and 36.0% at an advanced stage.Patients with advanced/relapsed OCCC who received platinum-based chemotherapy plus bevacizumab followed by maintenance bevacizumab had a median first-line progressionfree survival (PFS) of 12.2 months, compared with 9.3 months for chemotherapy alone (hazard ratio=0.69; 95% confidence interval [CI]=0.33, 1.45). In 27 patients who received an ICI, the overall response rate was 18.5% and median duration of response was 7.4 months (95% CI=6.5, 8.3). In 17 carefully selected patients with fewer than 3 sites of relapse, median PFS was 35 months (95% CI=0, 73.5) and median overall survival was 96.8 months (95% CI=44.6, 149.0) after SCS. NGS on 58 tumors revealed common mutations in ARID1A (48.3%), PIK3CA (46.6%), and KRAS (20.7%). Pathogenic alterations in PIK3CA, FGFR2, and NBN were associated with worse survival outcomes. Median tumor mutational burden was 3.78 (range, 0–16). All 26 patients with available loss of heterozygosity (LOH) scores had LOH <16%. Conclusion Our study demonstrates encouraging outcomes with bevacizumab and ICI, and SCS in select relapsed OCCC patients. Prospective trials are warranted.

Extensive research supported the therapeutic potential of curcumin, a naturally occurring compound, as a promising cytokinesuppressive anti-inflammatory drug. This study aimed to investigate the synergistic anti-inflammatory and anti-cytokine activities by combining 6-shogaol and 10-shogaol to curcumin, and associated mechanisms in modulating lipopolysaccharides and interferon-ɣ-induced proinflammatory signaling pathways. Our results showed that the combination of 6-shogaol-10-shogaol-curcumin synergistically reduced the production of nitric oxide, inducible nitric oxide synthase, tumor necrosis factor and interlukin-6 in lipopolysaccharides and interferon-γ-induced RAW 264.7 and THP-1 cells assessed by the combination index model. 6-shogaol-10-shogaol-curcumin also showed greater inhibition of cytokine profiling compared to that of 6-shogaol-10-shogaol or curcumin alone. The synergistic anti-inflammatory activity was associated with supressed NFκB translocation and downregulated TLR4-TRAF6-MAPK signaling pathway. In addition, SC also inhibited microRNA-155 expression which may be relevant to the inhibited NFκB translocation. Although 6-shogaol-10-shogaol-curcumin synergistically increased Nrf2 activity, the anti-inflammatory mechanism appeared to be independent from the induction of Nrf2. 6-shogaol-10-shogaol-curcumin provides a more potent therapeutic agent than curcumin alone in synergistically inhibiting lipopolysaccharides and interferon-γ induced proinflammatory mediators and cytokine array in macrophages. The action was mediated by the downregulation of TLR4/TRAF6/MAPK pathway and NFκB translocation.

INTRODUCTION: The identification of population-level healthcare needs using hospital electronic medical records (EMRs) is a promising approach for the evaluation and development of tailored healthcare services. Population segmentation based on healthcare needs may be possible using information on health and social service needs from EMRs. However, it is currently unknown if EMRs from restructured hospitals in Singapore provide information of sufficient quality for this purpose. We compared the inter-rater reliability between a population segment that was assigned prospectively and one that was assigned retrospectively based on EMR review. METHODS: 200 non-critical patients aged ≥ 55 years were prospectively evaluated by clinicians for their healthcare needs in the emergency department at Singapore General Hospital, Singapore. Trained clinician raters with no prior knowledge of these patients subsequently accessed the EMR up to the prospective rating date. A similar healthcare needs evaluation was conducted using the EMR. The inter-rater reliability between the two rating sets was evaluated using Cohen's Kappa and the incidence of missing information was tabulated. RESULTS: The inter-rater reliability for the medical 'global impression' rating was 0.37 for doctors and 0.35 for nurses. The inter-rater reliability for the same variable, retrospectively rated by two doctors, was 0.75. Variables with a higher incidence of missing EMR information such as 'social support in case of need' and 'patient activation' had poorer inter-rater reliability. CONCLUSION Pre-existing EMR systems may not capture sufficient information for reliable determination of healthcare needs. Thus, we should consider integrating policy-relevant healthcare need variables into EMRs.

OBJECTIVES: To compare and assess the performance of 6 osteoporosis risk assessment tools for screening osteoporosis in Malaysian postmenopausal women. METHODS: Six osteoporosis risk assessments tools (the Simple Calculated Osteoporosis Risk Estimation [SCORE], the Osteoporosis Risk Assessment Instrument, the Age Bulk One or Never Estrogen, the body weight, the Malaysian Osteoporosis Screening Tool, and the Osteoporosis Self-Assessment Tool for Asians) were used to screen postmenopausal women who had not been previously diagnosed with osteoporosis/osteopenia. These women also underwent a dual-energy X-ray absorptiometry (DXA) scan to confirm the absence or presence of osteoporosis. RESULTS: A total of 164/224 participants were recruited (response rate, 73.2%), of which only 150/164 (91.5%) completed their DXA scan. Sixteen participants (10.7%) were found to have osteoporosis, whilst 65/150 (43.3%) were found to have osteopenia. Using precision-recall curves, the recall of the tools ranged from 0.50 to 1.00, whilst precision ranged from 0.04 to 0.14. The area under the curve (AUC) ranged from 0.027 to 0.161. The SCORE had the best balance between recall (1.00), precision (0.04–0.12), and AUC (0.072–0.161). CONCLUSIONS: We found that the SCORE had the best balance between recall, precision, and AUC among the 6 screening tools that were compared among Malaysian postmenopausal women.
Absorptiometry, Photon ; Area Under Curve ; Body Weight ; Bone Diseases, Metabolic ; Estrogens ; Female ; Humans ; Malaysia ; Mass Screening ; Osteoporosis ; Risk Assessment ; Self-Assessment

The concept of theranostics, where individual patient-level biological information is used to choose the optimal therapy for that individual, has become more popular in the modern era of ‘personalised’ medicine. With the growth of theranostics, nuclear medicine as a specialty is uniquely poised to grow along with the ever-increasing number of concepts combining imaging and therapy. This special report summarises the status and growth of Theranostic Nuclear Medicine in Singapore.We will cover our experience with the use of radioiodine, radioiodinated metaiodobenzylguanidine, peptide receptor radionuclide therapy, prostate specific membrane antigen radioligand therapy, radium-223 and yttrium-90 selective internal radiation therapy.We also include a section on our radiopharmacy laboratory, crucial to our implementation of theranostic principles. Radionuclide theranostics has seen tremendous growth and we hope to be able to grow alongside to continue to serve the patients in Singapore and in the region.
Hope ; Humans ; Lutetium ; Membranes ; Nuclear Medicine ; Prostate ; Radium ; Receptors, Peptide ; Singapore ; Theranostic Nanomedicine ; Yttrium

The concept of theranostics, where individual patient-level biological information is used to choose the optimal therapy for that individual, has become more popular in the modern era of ‘personalised’ medicine. With the growth of theranostics, nuclear medicine as a specialty is uniquely poised to grow along with the ever-increasing number of concepts combining imaging and therapy. This special report summarises the status and growth of Theranostic Nuclear Medicine in Singapore.We will cover our experience with the use of radioiodine, radioiodinated metaiodobenzylguanidine, peptide receptor radionuclide therapy, prostate specific membrane antigen radioligand therapy, radium-223 and yttrium-90 selective internal radiation therapy.We also include a section on our radiopharmacy laboratory, crucial to our implementation of theranostic principles. Radionuclide theranostics has seen tremendous growth and we hope to be able to grow alongside to continue to serve the patients in Singapore and in the region.

Biopsy, Fine-Needle ; Diagnosis, Differential ; Facial Paralysis ; diagnosis ; etiology ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Parotid Gland ; pathology ; Sclerosis ; Sialadenitis ; diagnosis