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: Post-anaesthesia care unit (PACU) delirium affects 5%-45% of patients after surgery and is associated with postoperative delirium and increased mortality. Up to 40% of PACU delirium is preventable, but it remains under-recognised due to a lack of awareness of its diagnosis. The nursing delirium screening scale (Nu-DESC) has been validated for diagnosing PACU delirium, but is not routinely used locally. This study aimed to use Nu-DESC to establish the incidence and risk factors of PACU delirium in patients undergoing non-cardiac surgery in the surgical population. METHODS: We conducted an audit of eligible patients undergoing major surgery in three public hospitals in Singapore over 1 week. Patients were assessed for delirium 30-60 min following their arrival in PACU using Nu-DESC, with a total score of ≥2 indicative of delirium. RESULTS: A total of 478 patients were assessed. The overall incidence rate of PACU delirium was 18/478 (3.8%), and the incidence was 9/146 (6.2%) in patients aged > 65 years. Post-anaesthesia care unit delirium was more common in females, patients with malignancy and those who underwent longer operations. Logistic regression analysis showed that the use of bispectral index (P < 0.001) and the presence of malignancy (P < 0.001) were significantly associated with a higher incidence of PACU delirium. CONCLUSION In this first local study, the incidence of PACU delirium was 3.8%, increasing to 6.2% in those aged > 65 years. Understanding these risk factors will form the basis for which protocols can be established to optimise resource management and prevent long-term morbidities and mortality in PACU delirium.
Female ; Humans ; Delirium/epidemiology* ; Postoperative Complications/etiology* ; Singapore/epidemiology* ; Prospective Studies ; Anesthesia/adverse effects* ; Risk Factors ; Neoplasms

Purpose: Laparoscopic appendicectomy (LA) has several advantages over conventional open appendicectomy (OA). However, about 5% to 10% of LA patients still need to be converted to open surgery. Identifying risk factors that contribute to conversion to OA allows for early identification of patients who may benefit from primary OA. This study aimed to determine the conversion rate of LA to OA and to identify its associated risk factors among patients with acute or perforated appendicitis. Methods: A retrospective review of medical records was performed among patients with acute or perforated appendicitis who underwent LA between December 2015 and January 2017. With the use of multivariable logistic regression analyses, the predictors of conversion from laparoscopic to OA were investigated. Results: Out of 120 patients, 33 cases were converted to OA which gives a conversion rate of 27.5%. Among 33 patients who were converted to OA, 27 patients (81.8%) had perforated appendix, while in the LA group, perforated appendix cases consisted of 34.5% (P<0.001). Histopathology of the appendix was the predictor of conversion from LA to OA (adjusted odds ratio, 8.82; 95% confidence interval, 3.13–24.91; P<0.001). Conclusion The result from our study shows that the overall conversion rate for the study period was high. Patients with perforated appendicitis had a higher risk of conversion to OA. Therefore, preoperative diagnosis of perforated appendicitis may be paramount in predicting conversion to OA.

INTRODUCTION: Post-anaesthesia care unit (PACU) delirium is a potentially preventable condition that results in a significant long-term effect. In a multicentre prospective cohort study, we investigate the incidence and risk factors of postoperative delirium in elderly patients undergoing major non-cardiac surgery. METHODS: Patients were consented and recruited from 4 major hospitals in Singapore. Research ethics approval was obtained. Patients older than 65 years undergoing non-cardiac surgery >2 hours were recruited. Baseline perioperative data were collected. Preoperative baseline cognition was obtained. Patients were assessed in the post-anaesthesia care unit for delirium 30-60 minutes after arrival using the Nursing Delirium Screening Scale (Nu-DESC). RESULTS Ninety-eight patients completed the study. Eleven patients (11.2%) had postoperative delirium. Patients who had PACU delirium were older (74.6±3.2 versus 70.6±4.4 years, P=0.005). Univariate analysis showed those who had PACU delirium are more likely to be ASA 3 (63.6% vs 31.0%, P=0.019), had estimated glomerular filtration rate (eGFR) of >60mL/min/1.73m2 (36.4% vs 10.6%, P=0.013), higher HbA1C value (7.8±1.2 vs 6.6±0.9, P=0.011), raised random blood glucose (10.0±5.0mmol/L vs 6.5±2.4mmol/L, P=0.0066), and moderate-severe depression (18.2% vs 1.1%, P=0.033). They are more likely to stay longer in hospital (median 8 days [range 4-18] vs 4 days [range 2-8], P=0.049). Raised random blood glucose is independently associated with increased PACU delirium on multivariate analysis.
Aged ; Anesthesia ; Anesthesia Recovery Period ; Delirium/etiology* ; Humans ; Incidence ; Postoperative Complications/etiology* ; Prospective Studies ; Risk Factors

Cellular immunotherapy harnesses the body's own immune system to fight cancer by using engineered T cells, macrophages, or natural killer (NK) cells. Compared to chimeric antigen receptor T (CAR-T) cells that are commonly used to treat hematological malignancies, CAR-NK cells have shown remarkable therapeutic effectiveness while exhibiting enhanced safety, reduced risk of graft-versus-host disease, fewer side effects, and amplified antitumor efficacy. Preclinical trials have unveiled the high potential of adoptive CAR-NK cell therapy to curtail or even eliminate both hematological malignancies and solid tumors in animal models. We brought forth herein the design principle of CAR-NK cells, highlighted the latest progress in the preclinical testing and clinical trials of CAR-NK cells, briefly delved into discussed major roadblocks in CAR-NK therapy, and discussed potential solutions to surmount these challenges. Given the accelerated progress in both basic and translational studies on immune cell engineering, CAR-NK cell therapy promises to become a serious contender and important addition to the next-generation cell-based immunotherapy.

Cellular immunotherapy harnesses the body's own immune system to fight cancer by using engineered T cells, macrophages, or natural killer (NK) cells. Compared to chimeric antigen receptor T (CAR-T) cells that are commonly used to treat hematological malignancies, CAR-NK cells have shown remarkable therapeutic effectiveness while exhibiting enhanced safety, reduced risk of graft-versus-host disease, fewer side effects, and amplified antitumor efficacy. Preclinical trials have unveiled the high potential of adoptive CAR-NK cell therapy to curtail or even eliminate both hematological malignancies and solid tumors in animal models. We brought forth herein the design principle of CAR-NK cells, highlighted the latest progress in the preclinical testing and clinical trials of CAR-NK cells, briefly delved into discussed major roadblocks in CAR-NK therapy, and discussed potential solutions to surmount these challenges. Given the accelerated progress in both basic and translational studies on immune cell engineering, CAR-NK cell therapy promises to become a serious contender and important addition to the next-generation cell-based immunotherapy.

Anesthesia/adverse effects* ; Anesthesiology ; Humans ; Neuromuscular Monitoring

General Hospital. In all 167 of them wereadministered with TXA and another 167 of the patients werenot. The primary outcome expected is the number of goodoutcomes in isolated TBI patients given TXA. Goodoutcome is defined by Glasgow Outcome Score-Extended(GOSE) of five and above. Secondary outcome was clotexpansion of an intracranial bleed seen on the first scan thathad expanded by 25% or more on any dimension on thesecond scan. Results: The TXA did not show significant trend of goodoutcome in terms of GOSE (p=0.763). However, for moderateand severe acute subdural haemorrhage (SDH) subgroups,there was a significant difference (p=0.042). Clot expansionwas present in 14 patients (12.7%) with TXA given and in 54patients (38.8%) without TXA. The difference wasstatistically significant (p<0.001). Of the patients whoreceived TXA, there was one case (0.6%) of deep veinthrombosis. Apart from that, TXA showed non-significanttrend in reducing mortality (p=0.474). Conclusions: Tranexamic acid reduces the rate of clotexpansion in TBI by 26.1% (38.8-12.7%) without significantlyincreasing the risk of a thrombotic event. It can also improvethe outcome of moderate and severe TBI patients with acuteSDH.