Background The effect of extracellular microenvironment (hypoxia and pH) has been regarded as a key hallmark in cancer progression. The study aims to investigate the effects of carbonic anhydrase IX (CAIX), a key hypoxia-inducible marker, in triple-negative breast cancer (TNBC) in correlation with clinicopathological parameters and predicting survival outcomes. Methods A total of 323 TNBC cases diagnosed at the Department of Anatomical Pathology, Singapore General Hospital from 2003 to 2013 were used. Immunohistochemical staining (IHC) was performed using CAIX antibody and digital mRNA quantification was performed using NanoString assays. CAIX membranous expression was correlated with clinicopathological parameters using Chi-squared test or Fisher’s exact tests. Disease-free survival (DFS) and overall-survival (OS) were estimated using Kaplan–Meier analysis and compared between groups with the log-rank test. Results Forty percent of TNBCs were observed to express CAIX protein and demonstrated significant association with larger tumour size (P = 0.002), higher histological grade (P < 0.001), and significantly worse disease-free survival (DFS) and overall survival (OS) (after adjustment: HR = 2.99, 95% CI = 1.78–5.02, P < 0.001 and HR = 2.56, 95% CI = 1.41–4.65, P = 0.002, respectively). Gene ontology enrichment analysis revealed six significantly enriched cellular functions (secretion, cellular component disassembly, regulation of protein complex assembly, glycolytic process, cellular macromolecular complex assembly, positive regulation of cellular component biogenesis) associated with genes differentially expressed (CAIX, SETX, WAS, HK2, DDIT4, TUBA4α, ARL1). Three genes (WAS, SETX and DDIT4) were related to DNA repair, indicating that DNA stability may be influenced by hypoxia in TNBC. Conclusions Our results demonstrate that CAIX appears to be a significant hypoxia-inducible molecular marker and increased CAIX protein levels are independently associated with poor survival in TNBC. Identification of CAIX-linked seven gene-signature and its relationship with enriched cellular functions further support the implication and influence of hypoxia-mediated CAIX expression in TNBC tumour microenvironment.

No abstract

No abstract

Objectives: In healthcare facilities, environmental reservoirs of CPE are associated with CPE outbreaks. In the newly built NCID building, we studied the introduction of CPE in the aqueous environment. Methods: We sampled the aqueous environments (ie, sink, sink strainer, and shower drain-trap with Copan E-swabs and sink P-trap water) of 4 NCID wards (ie, 2 multidrug-resistant organism (MDRO) wards and 2 non-MDRO wards). Two sampling cycles (cycle 1, June–July 2019 and cycle 2, September–November 2019) were conducted in all 4 wards. Cycle 3 (November 2020) was conducted in 1 non-MDRO ward to investigate CPE colonization from previous cycles. Enterobacterales were identified using MALDI-TOF MS and underwent phenotypic (mCIM and eCIM) and confirmatory PCR tests for CPE. Results: We collected 448, 636, and 96 samples in cycles 1, 2, and 3, respectively. MDRO and non-MDRO wards were operational for 1 and 7 months during the first sampling cycle. The CPE prevalence rates in MDRO wards were 1.67% (95% CI, 0.46% – 4.21%) in cycle 1 and 1.76% (95% CI, 0.65% – 3.80%) in cycle 2. In the aqueous environments in MDRO wards, multiple species were detected (cycle 1: 2 K. pneumoniae, 1 E. coli, and 1 S. marcescens; cycle 2: 5 K. pneumoniae and 1 R. planticola), and multiple genotypes were detected (cycle 1: 3 blaOXA48; cycle 2: 5 blaOXA48 and 1 blaKPC). The CPE prevalence in non-MDRO wards was 1.92% (95% CI, 0.53%–4.85%) in cycle 1. The prevalence rate increased by 5.51% (95% CI, 1.99%–9.03%) to 7.43% (95% CI, 4.72%–11.04%; P = .006) in cycle 2, and by another 2.98% (95% CI, −3.82% to 9.79%) to 10.42% (95% CI, 5.11% – 18.3%; P = .353) in cycle 3. Only blaOXA48 S. marcescens were detected in all cycles (except 1 blaOXA48 K. pneumoniae in cycle 2) in the non-MDRO ward. Conclusions: CPE established rapidly in the aqueous environment of NCID wards, more so in MDRO wards than non-MDRO wards. Longitudinal studies to understand the further expansion of the CPE colonization and its impact on patients are needed.

Objectives: Over the past 2 years, many infection prevention and control (IPC) resources have been diverted to manage the COVID-19 pandemic. Its impact on the incidence of antimicrobial-resistant organisms has not been adequately studied. We investigated the impact of the pandemic on the incidence of carbapenem-resistant Enterobacterales (CRE) in Singapore. Methods: We extracted data on unique CRE isolates (clinical and/or surveillance cultures) and patient days for 6 public hospitals in Singapore from the carbapenemase-producing Enterobacteriaceae (CaPES) study group database, and we calculated the monthly incidence of CRE (per 10,000 patient days). Interrupted time-series (ITS) analysis was conducted with the pre–COVID-19 period defined as before February 2020, and the COVID-19 period defined as after February 2020. Statistical analyses were performed using Stata version 15 software. Results: From January 2017 to March 2021, 6,770 CRE isolates and 9,126,704 patient days were documented. The trend in CRE monthly incidence increased significantly during the pre–COVID-19 period (0.060; 95% CI, 0.033–0.094; P < .001) but decreased during the COVID-19 period (−0.183; 95% CI, −0.390 to 0.023; P = .080) without stepwise change in the incidence (−1.496; 95% CI, −3.477 to 0.485; P = .135). The trend in monthly incidence rate of CRE clinical cultures increased significantly during the pre–COVID-19 period (0.046; 95% CI, 0.028–0.064; P < .001) and decreased significantly during COVID-19 period (−0.148; 95% CI, −0.249 to −0.048; P = .048) with no stepwise change in the incidence (−0.063; 95% CI, −0.803 to 0.677; P = .864). The trend in monthly incidence rate of CRE surveillance cultures decreased during the pre–COVID-19 period (−0.020; 95% CI, −0.062 to 0.022; P = .341) and the COVID-19 period (−0.067; 95% CI, −0.291to 0.158; P = .552) without stepwise change in the incidence (−1.327; 95% CI, −3.535 to 0.881; P = .233). Conclusions: The rate of CRE in clinical cultures decreased during COVID-19 but not the rate in surveillance cultures. Further studies are warranted to study the impact of COVID-19 on CREs.(DUPLICATE DELETED)