Objective: With the development of novel antibody-drug conjugates (ADCs), folate receptor alpha (FOLR1) is a promising therapeutic target for the treatment of platinum-resistant tuboovarian carcinomas. The main aims of this study were to assess FOLR1 protein expression in a large cohort of ovarian carcinoma histotypes. To inform future clinical trial design we identified molecular correlates of FOLR1 expression in low-grade serous carcinoma (LGSC). Methods: One thousand five hundred forty-seven ovarian carcinoma samples from 5 different Canadian cohorts were successfully evaluated by immunohistochemistry for FOLR1 expression using the PS2+ system. Statistical analyses with clinicopathological parameters, LGSC molecular subtypes, and overall survival (OS) were performed. Results: High FOLR1 expression was detected in 44% of high-grade serous carcinomas, and in 30% LGSC, 8% clear cell, 6% endometrioid, and 0% mucinous and/or mesonephrictype adenocarcinomas. In 160 LGSC cases, FOLR1 expression was more frequent in cases with normal MAPK pathway status (37% MAPK wild type vs. 14% canonical MAPK pathway mutations; p=0.002), low progesterone receptor (PR) expression (41%) vs. 23% (Allred score >2; p=0.02), and p16 loss (48% p16 absent vs. 26% normal; p=0.03). Canonical MAPK mutation status and PR expression remained significant on multivariable analysis. No significant associations between OS and FOLR1 expression were observed. Conclusion A significant proportion of LGSC express high FOLR1 levels supporting the development of clinical trials to investigate ADCs targeting FOLR1 as novel agents for treating this disease. In LGSC, high FOLR1 expression was associated with fewer MAPK pathway alterations, low PR expression, and p16 loss.

INTRODUCTION: Frontline healthcare workers (HCWs) exposed to coronavirus disease 2019 (COVID-19) are at risk of psychological distress. This study evaluates the psychological impact of COVID-19 pandemic on HCWs in a national paediatric referral centre. METHODS: This was a survey-based study that collected demographic, work environment and mental health data from paediatric HCWs in the emergency, intensive care and infectious disease units. Psychological impact was measured using the Depression, Anxiety, Stress Scale-21. Multivariate regression analysis was performed to identify risk factors associated with psychological distress. RESULTS: The survey achieved a response rate of 93.9% (430 of 458). Of the 430 respondents, symptoms of depression, anxiety and stress were reported in 168 (39.1%), 205 (47.7%) and 106 (24.7%), respectively. Depression was reported in the mild (47, 10.9%), moderate (76, 17.7%), severe (23, 5.3%) and extremely severe (22, 5.1%) categories. Anxiety (205, 47.7%) and stress (106, 24.7%) were reported in the mild category only. Collectively, regression analysis identified female sex, a perceived lack of choice in work scope/environment, lack of protection from COVID-19, lack of access to physical activities and rest, the need to perform additional tasks, and the experience of stigma from the community as risk factors for poor psychological outcome. CONCLUSION A high prevalence of depression, anxiety and stress was reported among frontline paediatric HCWs during the COVID-19 pandemic. Personal psychoneuroimmunity and organisational prevention measures can be implemented to lessen psychiatric symptoms. At the national level, involving mental health professionals to plan and coordinate psychological intervention for the country should be considered.
Adult ; Anxiety/etiology* ; COVID-19/psychology* ; Depression/etiology* ; Female ; Health Surveys ; Hospitals, Pediatric ; Humans ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Occupational Diseases/etiology* ; Pandemics ; Personnel, Hospital/psychology* ; Prevalence ; Risk Factors ; Self Report ; Severity of Illness Index ; Singapore/epidemiology* ; Stress, Psychological/etiology*

BACKGROUND/AIMS: Inflammation-based scores, such as the neutrophil-to-lymphocyte ratio (NLR), have been associated with prognosis in hepatocellular carcinoma (HCC); but variable cut-off values and potential lack of specificity have limited the utility of NLR. This study evaluates NLR in a large cohort of HCC patients. METHODS: We retrospectively reviewed 789 HCC cases (1993–2017) for demographics, tumor characteristics, treatment, and survival. NLR was stratified into NLR ≥1.5 and NLR ≥3 and analyzed for correlation with American Joint Committee on Cancer (AJCC) and Barcelona Clinic Liver Cancer (BCLC) stages. In 235 patients who underwent liver resection, survival and recurrence were evaluated by NLR. RESULTS: In 789 HCC cases, mean NLR was increased with advanced AJCC and BCLC stages. Hepatitis C patients were less likely to have NLR ≥1.5 and ≥3. Non-alcoholic steatohepatitis patients were more likely to have NLR ≥3. Patients with tumor size >5 cm, rupture, or macrovascular invasion were more likely to have NLR ≥3. In patients treated with resection, NLR ≥3 predicted early recurrence (odds ratio [OR] 4.14, P<0.01) and overall recurrence (OR 4.05, P<0.01). Mean NLR was 4.30 in those with recurrence and 2.75 in those without recurrence. Patients with NLR ≥3 showed significantly worse survival compared to those with NLR <3 (P<0.01 by log-rank test). CONCLUSIONS: Elevated NLR is associated with advanced cancer stage and aggressive tumor characteristics, such as large size, rupture, and invasion. NLR ≥3 was associated with early and overall recurrence after resection but varied with etiology. NLR may be a useful biomarker in predicting recurrence for HCC patients undergoing curative resection, but further studies are required to elucidate the effect of disease etiology.
Carcinoma, Hepatocellular ; Cohort Studies ; Demography ; Fatty Liver ; Hepatitis C ; Humans ; Joints ; Liver Diseases ; Liver Neoplasms ; Liver ; Prognosis ; Recurrence ; Retrospective Studies ; Rupture ; Sensitivity and Specificity

BACKGROUND/AIMS: Surveillance for hepatocellular carcinoma (HCC) with ultrasound in high-risk populations is generally believed to improve opportunities for treatment. However, tumors are still missed due to various factors. This study explores success versus failure of HCC surveillance. METHODS: This is a retrospective study of 1,125 HCC cases. Categories considered for successful detection were largest tumor ≤3.0 cm, single tumors ≤3.0 cm and ≤2.0 cm, and adherence to Milan criteria. Examined factors were age <60 years, gender, rural residence, body-mass index (BMI), hepatitis infection, smoking, diabetes, hyperlipidemia, cirrhosis, ascites, and Model for End-Stage Liver Disease <10. RESULTS: HCC was found on surveillance in 257 patients with a mean tumor size of 3.17 cm; multiple tumors were seen in 28% of cases, bilateral tumors in 7.4%, and vascular invasion in 3.7%. Surveillance was successful in 61.5% of cases involving a largest tumor ≤3.0 cm, with BMI ≥35 negatively affecting detection (odds ratio [OR] 0.28, P=0.014) and cirrhosis positively affecting detection (OR 2.31, P=0.036). Ultrasound detected 19.1% of single tumors ≤2.0 cm with ascites improving the detection rate (OR 3.89, P=0.001). Finally, adherence to Milan criteria occurred in 75.1% of cases, revealing negative associations with diabetes (OR 0.48, P=0.044 and male gender (OR 0.49, P=0.08). CONCLUSIONS: Although surveillance is recommended for HCC, not all surveillance ultrasound are ideal. Tumor detection can depend on gender, BMI, diabetes, cirrhosis, and ascites and is achieved in 19.1–75% of cases depending on the definition of success. Closer follow-up or additional imaging might be necessary for some patient subgroups.
Ascites ; Carcinoma, Hepatocellular* ; Early Detection of Cancer ; Fibrosis ; Follow-Up Studies ; Hepatitis ; Humans ; Hyperlipidemias ; Liver Diseases ; Male ; Population Surveillance ; Retrospective Studies ; Smoke ; Smoking ; Ultrasonography

Stroke is a major cause of death and disability in Singapore and many parts of the world. Chronic disease management programmes allow seamless care provision across a spectrum of healthcare facilities and allow appropriate services to be brought to the stroke patient and the family. Randomised controlled trials have provided evidence for efficacious interventions. After the management of acute stroke in a stroke unit, most stable stroke patients can be sent to their family physician for continued treatment and rehabilitation supervision. Disabled stroke survivors may need added home-based services. Suitable community resources will need to be harnessed. Clinic-based stroke nurses may enhance service provision and coordination. Close collaboration between the specialist and family physician would be needed to right-site patients and also allow referrals in either direction where necessary. Barriers to integration can be surmounted by trust and improved communication. Audits would allow monitoring of care provision and quality care enhancement. The Wagner model of chronic care delivery involves self-management support, shared clinical information systems, delivery system redesign, decision support, healthcare organisation and community resources. The key and critical feature is the need for an informed, activated (or motivated) patient, working in collaboration with the specialist and family physician, and a team of nursing and allied healthcare professionals across the continuum of care. The 3-year Integrating Services and Interventions for Stroke (ISIS) project funded by the Ministry of Health will test such an integrative system.
Delivery of Health Care, Integrated ; organization & administration ; Evidence-Based Medicine ; Humans ; Ischemic Attack, Transient ; Medicine ; Middle Aged ; Models, Organizational ; Neurology ; Primary Health Care ; Rehabilitation Nursing ; Singapore ; Specialization ; Stroke ; nursing ; Stroke Rehabilitation