Duration-response association between occupational exposure and pancreatic cancer risk: meta-analysis.

BACKGROUND: Evidence is lacking on the occupational exposure time window to chemical agents related to pancreatic cancer risk. AIMS: This study performed meta-regression and meta-analysis to examine the dose-response association between occupational exposure duration to chemical agents and pancreatic cancer risk. METHODS: We searched and reviewed studies on exposure duration and pancreatic cancer in five databases (Cochrane Library, EMBASE, PubMed, ScienceDirect and Web of Science) from inception to 16 May 2022. Exposure refers to the years a worker was exposed to any chemical agent, and outcome variables were pancreatic cancer incidence and mortality. RESULTS: We identified 31 studies, including 288 389 participants. In the meta-regression, the positive dose-response association indicated pancreatic cancer risk increased slightly with every additional year of exposure duration (slope = 1.01; 95% confidence interval [CI] 1.00-1.02). Pancreatic cancer risk increased with an exposure duration of 1-10 (relative risk [RR] = 1.04; 95% CI 1.02-1.06), 11-20 (RR = 1.11; 95% CI 1.05-1.16), and 21-30 years (RR = 1.39; 95% CI 1.12-1.73). CONCLUSIONS: Pancreatic cancer risk increased as occupational exposure duration increased, with an exposure time window ranging from 1 to 30 years.

Lung cancer screening study from a smoking population in Kunming.

OBJECTIVE: Yunnan, China, is a central tobacco-producing region with a large smoking population and an increasing incidence of lung cancer in recent years. This study aimed to understand the incidence of lung cancer and the characteristics of lung nodules on low-dose computed tomography (LDCT) scans of the chest in a long-term smoking population in Kunming. PATIENTS AND METHODS: Long-term smokers in Kunming who were not at risk of evident lung disease symptoms were recruited through recommendation and publicity by the Kunming University of Science and Technology. RESULTS: Among 375 cases eligible for inclusion,14 cases of lung cancer were detected with a detection rate of 3.73% (95% CI: 2.55%-4.27%), including one case of squamous carcinoma, one case of small cell lung cancer, seven cases of adenocarcinoma of the lung and five cases of early-stage lung cancer (35.71%). In the group of < 6 mm solid nodules and < 5 mm non-solid nodules, no lung cancer was detected in 201 cases; lung cancer was detected in 14 cases in 61 cases, and there was a statistical difference between the two groups (p < 0.05). CONCLUSIONS: The lung cancer detection rate in long-term smokers was high, with the type predominantly adenocarcinoma and a high incidence of lung nodules, and increased when solid nodules≥6 mm or non-solid nodules ≥ 5 mm were present. It is recommended that screening for lung cancer by LDCT of the chest be introduced in the male smoking population who meet the risk factors and that screening for lung cancer in women should be redefined as a high-risk factor.

Targeted amplification and MinION nanopore sequencing of key azole and echinocandin resistance determinants of clinically relevant Candida spp. from blood culture bottles.

The objective of the study was to evaluate the use of targeted multiplex Nanopore MinION amplicon re-sequencing of key Candida spp. from blood culture bottles to identify azole and echinocandin resistance associated SNPs. Targeted PCR amplification of azole (ERG11 and ERG3) and echinocandin (FKS) resistance-associated loci was performed on positive blood culture media. Sequencing was performed using MinION nanopore device with R9.4.1 Flow Cells. Twenty-eight spiked blood cultures (ATCC strains and clinical isolates) and 12 prospectively collected positive blood cultures with candidaemia were included. Isolate species included Candida albicans, Candida glabrata, Candida krusei, Candida parapsilosis, Candida tropicalis and Candida auris. SNPs that were identified on ERG and FKS genes using Snippy tool and CLC Genomic Workbench were correlated with phenotypic testing by broth microdilution (YeastOne™ Sensititre). Illumina whole-genome-sequencing and Sanger-sequencing were also performed as confirmatory testing of the mutations identified from nanopore sequencing data. There was a perfect agreement of the resistance-associated mutations detected by MinION-nanopore-sequencing compared to phenotypic testing for acquired resistance (16 with azole resistance; 3 with echinocandin resistance), and perfect concordance of the nanopore sequence mutations to Illumina and Sanger data. Mutations with no known association with phenotypic drug resistance and novel mutations were also detected.

[The 484th case:asthma, limb numbness, diplopia, headache].

A 47-year-old female who had a history of asthma and sinusitis in the past was admitted to hospital with limbs numbness and pain for ten days. The symptoms were aggravated for eight hours. On admission, significant peripheral eosinophilia was noted. Paranasal sinusitis and transient bronchiolitis were found by CT scan.Electromyogram demonstrated multiple mononeuropathy. Eosinophilia was indicated by bone marrow biopsy. The diagnosis of eosinophilic granulomatous polyangiitis(EGPA) was determined. The patient got better after applying glucocorticoid and cyclophosphamide.Later she developed abdominal pain and partial oculomotor nerve palsy, while her condition improved after continued immunosuppression and anticoagulant therapy. She was hospitalized for the third time because of headache. Subarachnoid hemorrhage was diagnosed after lumber puncture and cranial MRI+MRA+MRV and other examinations. She was relieved after conservative treatment. Subarachnoid hemorrhage with EGPA is rare. This case may improve physicians' understanding of EGPA complicated with subarachnoid hemorrhage.

Association Between Minimum Inhibitory Concentration, Beta-lactamase Genes and Mortality for Patients Treated With Piperacillin/Tazobactam or Meropenem From the MERINO Study.

INTRODUCTION: This study aims to assess the association of piperacillin/tazobactam and meropenem minimum inhibitory concentration (MIC) and beta-lactam resistance genes with mortality in the MERINO trial. METHODS: Blood culture isolates from enrolled patients were tested by broth microdilution and whole genome sequencing at a central laboratory. Multivariate logistic regression was performed to account for confounders. Absolute risk increase for 30-day mortality between treatment groups was calculated for the primary analysis (PA) and the microbiologic assessable (MA) populations. RESULTS: In total, 320 isolates from 379 enrolled patients were available with susceptibility to piperacillin/tazobactam 94% and meropenem 100%. The piperacillin/tazobactam nonsusceptible breakpoint (MIC >16 mg/L) best predicted 30-day mortality after accounting for confounders (odds ratio 14.9, 95% confidence interval [CI] 2.8-87.2). The absolute risk increase for 30-day mortality for patients treated with piperacillin/tazobactam compared with meropenem was 9% (95% CI 3%-15%) and 8% (95% CI 2%-15%) for the original PA population and the post hoc MA populations, which reduced to 5% (95% CI -1% to 10%) after excluding strains with piperacillin/tazobactam MIC values >16 mg/L. Isolates coharboring extended spectrum ß-lactamase (ESBL) and OXA-1 genes were associated with elevated piperacillin/tazobactam MICs and the highest risk increase in 30-day mortality of 14% (95% CI 2%-28%). CONCLUSIONS: After excluding nonsusceptible strains, the 30-day mortality difference from the MERINO trial was less pronounced for piperacillin/tazobactam. Poor reliability in susceptibility testing performance for piperacillin/tazobactam and the high prevalence of OXA coharboring ESBLs suggests that meropenem remains the preferred choice for definitive treatment of ceftriaxone nonsusceptible Escherichia coli and Klebsiella.

Donor-Derived Candida dubliniensis Resulting in Perigraft Abscesses in a Liver Transplant Recipient Proven by Whole Genome Sequencing: A Case Report.

BACKGROUND: The transmission of fungi via transplant, although well-known, has not often been molecularly proven. We describe a case of donor-derived candidiasis verified by whole genome sequencing. CASE DESCRIPTION: The multiorgan donor was a 42-year-old woman with subdural hemorrhage. Procurement of the thoracic organs was performed followed by the abdominal organs. Tissue from the left bronchus grew Candida dubliniensis. The liver recipient was a 63-year-old woman with cryptogenic liver cirrhosis. She was noted to have worsening leukocytosis on postoperative day (POD) 9. Computed tomography of the abdomen and pelvis showed multiple rim-enhancing collections around the graft. Percutaneous drainage was performed. Fluid cultures grew C dubliniensis. C dubliniensis isolated from the donor's left bronchus and the liver recipient's abscesses were verified to be related by whole genome sequencing. We postulate that C dubliniensis colonizing the donor's transected trachea could have contaminated the inferior vena cava when the former was left open after explant of the donor's lungs. A portion of the donor's contaminated inferior vena cava was transplanted along with the liver graft, resulting in the infected collections in the recipient. CONCLUSIONS: Our case report highlights the importance of maintaining a sterile field during organ procurement, especially in a multiorgan donor whose organs are explanted in succession.

[Apoptosis and expression of Caspase 3 and Caspase 4 in neurocytes of refractory human temporal lobe epilepsy].

OBJECTIVE: To study apoptosis and expression of Caspase 3 and Caspase 4 in temporal lobe neurocytes of refractory human temporal lobe epilepsy (TLE). METHODS: The temporal tissue samples were obtained from 30 cases of refractory TLE (TLE group) and 10 cases of brain trauma (contrast group) between January 1993 and May 2008. The surgical specimens were paraffin-embedded samples from Department of Pathology of Fujian Medical University and Department of Neurosurgery, the First Affiliated Hospital of Fujian Medical University. S-P staining of immunohistochemistry was used to detect the expression of Caspase 3 and Caspase 4 in temporal lobe neurocytes of TLE group and contrast group. Their expression was then analyzed. The terminal deoxynucleoitidyl transferase-mediated dUTP nick end labeling (TUNEL) staining was performed to visualize and analyze the neurocytes' apoptosis of two groups. RESULTS: The expression of Caspase 3 and Caspase 4 in neurocytes of TLE group were both higher than that of contrast group (t=12.905, P<0.01; t=11.880, P<0.01). The apoptotic index (AI) of neurocytes in TLE group also increased than that of contrast group (t=9.664, P<0.01). CONCLUSION: Caspase 3 and Caspase 4 may mediate neurocytes apoptosis in temporal lobe tissue of refractory human TLE.

Performance of case definitions for influenza surveillance.

Influenza-like illness (ILI) case definitions, such as those from the European Centre for Disease Control and Prevention, World Health Organization (WHO) and United States Centers for Disease Control and Prevention, are commonly used for influenza surveillance. We assessed how various case definitions performed during the initial wave of influenza A(H1N1) pdm09 infections in Singapore on a cohort of 727 patients with two to three blood samples and whose symptoms were reviewed fortnightly from June to October 2009. Using seroconversion (≥ 4-fold rise) to A/California/7/2009 (H1N1), we identified 36 presumptive influenza A(H1N1)pdm09 episodes and 664 episodes unrelated to influenza A(H1N1)pdm09. Cough, fever and headache occurred more commonly in presumptive influenza A(H1N1)pdm09. Although the sensitivity was low (36%), the recently revised WHO ILI case definition gave a higher positive predictive value (42%) and positive likelihood ratio (13.3) than the other case definitions. Results including only episodes with primary care consultations were similar. Individuals who worked or had episodes with fever, cough or sore throat were more likely to consult a physician, while episodes with Saturday onset were less likely, with some consultations skipped or postponed. Our analysis supports the use of the revised WHO ILI case definition, which includes only cough in the presence of fever defined as body temperature ≥ 38 °C for influenza surveillance.

Determinants of cerebral white matter changes in patients with stroke.

BACKGROUND/AIM: Cerebral white matter changes (WMC) are commonly observed in magnetic resonance imaging (MRI) scans of elderly people. Information about the prevalence of WMC is limited, and little is known about site-specific risk factors for the subcortical and periventricular regions in patients with ischaemic stroke. The study aims to analyse the prevalence and severity of WMC and investigate the risk factors of periventricular WMC (PVWMC) and deep WMC (DWMC) separately in patients with ischaemic stroke. METHODS: The data were collected between January and December 2013 from a medical centre in southern Taiwan. Every patient underwent a cerebral MRI scan, and WMC was separately rated as PVWMC and DWMC by using the modified Fazekas scale. RESULTS: In total, 527 patients who had experienced ischaemic stroke were included. The mean age of the patients was 67.0 ± 12.5 years (range: 31-94) and 62% of them were men. The mean age was significantly different among the four grades of severity in both the PVWMC (P < 0.001) and DWMC (P < 0.001) groups after adjustments for sex and vascular risk factors. Hypertension was independently correlated with severity of DWMC (P = 0.032) but not with PVWMC (P = 0.222). In multiple logistic regressions model, hypertension was a significant independent indicator of DWMC (odds ratio = 4.30; 95% confidence interval = 1.70-10.89). CONCLUSION: Our results suggest a region-specific pathogenesis of cerebral white matter in Asian patients with ischaemic stroke that may differ from those in the general population.

The emergence of community-onset Clostridium difficile infection in a tertiary hospital in Singapore: a cause for concern.

Increasing rates of Clostridium difficile infection (CDI) among those without traditional risk factors have been reported mainly in Europe and North America. Here we describe the epidemiology, clinical features and ribotypes of CDI at National University Hospital (NUH), a 1000-bed tertiary care hospital in Singapore, from December 2011 to May 2012. All laboratory-confirmed CDI cases ≥21 years old who gave informed consent were included. Clinical data were collected prospectively and participants underwent an interviewer-administered questionnaire. Cases were classified by healthcare facility exposure and severity according to the SHEA guidelines. Included cases were also subjected to PCR and were classified by ribotype. In total, 66 patients participated in the study, of which 33 (50.0%) were healthcare-facility-associated hospital onset (HCFA-HO). Of the 33 community-onset (CO) cases, 14 (42.4%) were HCFA-CO, 10 (30.3%) were indeterminate and 9 (27.3%) were community-associated (CA). Of the CA cases, a majority (90.9%) had prior exposure to a healthcare facility within the last 12 weeks. Clinical characteristics, exposures and outcomes were not different between HO-CDI and CO-CDI. Diagnosis was delayed in CO-CDI compared with HO-CDI (4 days vs. 1 day; P=0.014). There was no difference in distribution of ribotypes between CO-CDI and HO-CDI, with 053 being most prevalent in both groups. CO-CDI increasingly contributes to the burden of CDI in NUH. This may reflect a trend in other parts of Asia. Healthcare professionals should be aware of the possible role of outpatient healthcare environments to CDI risk and thus extend control measures to outpatient settings.

Sustained meticillin-resistant Staphylococcus aureus control in a hyper-endemic tertiary acute care hospital with infrastructure challenges in Singapore.

BACKGROUND: Meticillin-resistant Staphylococcus aureus (MRSA) has been entrenched in Singapore hospitals since the 1980s, with an excess of 600 non-duplicate cases of infections (120 bacteraemia episodes) each year in our 995-bed university hospital. Approximately 5% of our hospital beds are used as isolation facilities. AIM: To study the impact of an MRSA control bundle that was implemented via gradual geographic extension across hospital wards. METHODS: The bundle included active surveillance on admission and transfer/discharge to identify ward-based acquisition of MRSA, isolation and cohorting of MRSA-infected patients, enhanced hand hygiene initiatives, and publicly displayed feedback of MRSA acquisition and hand hygiene compliance rates. Implementation was between October 2006 and June 2010 in order to provide lead-time for the incremental development of infrastructural capacity, and to develop an ethic of infection prevention among staff. Results were analysed via interrupted time-series analysis. FINDINGS: MRSA infections fell midway through the implementation, with MRSA bacteraemia declining from 0.26 [95% confidence interval (CI): 0.18-0.34] cases per 1000 inpatient-days in the first quarter of 2004 to 0.11 (95% CI: 0.07-0.19) cases per 1000 inpatient-days in the first quarter of 2012. MRSA acquisition rates fell a year after the programme had been fully implemented, whereas hand hygiene compliance rose significantly from 47% (95% CI: 44-49) in the first quarter of 2009 to 69% (95% CI: 68-71) in the first quarter of 2012. CONCLUSION: Successful staged implementation of an MRSA bundle in a hyper-endemic setting is sustainable and represents a model that may be adapted for similar settings.

Bad design, bad practices, bad bugs: frustrations in controlling an outbreak of Elizabethkingia meningoseptica in intensive care units.

BACKGROUND: Elizabethkingia meningoseptica is a nosocomial-adapted Gram-negative bacillus intrinsically resistant to antibiotics commonly used in the intensive care setting. An outbreak investigation commenced when five patients developed E. meningoseptica infection in two intensive care units (ICUs). METHODS: Analysis of laboratory data, case reviews, ICU workflows and extensive environmental sampling were undertaken. Molecular typing was performed using repetitive element palindromic polymerase chain reaction. Follow-up studies after interventions included environmental monitoring and a survey of staff compliance with interventions. FINDINGS: Laboratory data revealed increasing incidence of E. meningoseptica colonization or infection in ICU patients compared with preceding years. E. meningoseptica was cultured from 44% (35/79) of taps, but not from other sources. Hand hygiene sinks were used for disposal of patient secretions and rinsing re-usable patient care items. Sinks misused in this way were contaminated more often than sinks that were not misused (odds ratio 4.38, 95% confidence interval 1.68-11.39; P = 0.004). Molecular typing revealed that patient isolates had identical patterns to several isolates from hand hygiene taps. An urgent education programme was instituted to change these practices. Taps were cleaned systematically and aerators were changed. A temporary reduction in case numbers was achieved. Recolonization of taps was demonstrated on follow-up environmental screening, and cases recurred after two months. A survey revealed that 77.3% (163/213) of nursing staff still misused sinks due to time constraints or other problems adhering to the interventions. CONCLUSION: Introduction of non-sanctioned practices due to suboptimal unit design may have unintentional consequences for ICU patients. Room design and staff workflows must be optimized for patient safety as lapses in procedure can inadvertently put patients at risk.

Emergence of Klebsiella pneumoniae co-producing NDM-type and OXA-181 carbapenemases.

The emergence of carbapenemase-producing Enterobacteriaceae is a rapidly evolving threat worldwide. Here, we report the molecular characterization of two Klebsiella pneumoniae isolates carrying both bla(OXA -181) and bla(NDM -1) or bla(NDM -5) isolated from epidemiologically unrelated patients in Singapore. The bla(OXA -181) genes were found existing in different genetic environments.

Emergence of clinical Klebsiella pneumoniae producing OXA-232 carbapenemase in Singapore.

We report the emergence of OXA-232, a newly described OXA-48-like carbapenemase variant, in Southeast Asia. Molecular characterization of eight Klebsiella pneumoniae obtained from local and foreign patients reveals clonality of the isolates. bla OXA-232 was located on a non-conjugative plasmid of 6141 base pairs (GenBank accession number JX423831.1).

Hot and steamy: outbreak of Bacillus cereus in Singapore associated with construction work and laundry practices.

BACKGROUND: A sudden increase in invasive infections caused by Bacillus cereus group organisms prompted an investigation at the National University Hospital in Singapore. AIM: To describe the investigation and management and subsequent difficulties controlling the outbreak. METHODS: Clinical case reviews were performed on all patients with B. cereus group recovered from clinical samples. Widespread environmental sampling was performed followed by review of hospital ventilation systems, domestic cleaning and laundry practices. FINDINGS: B. cereus was recovered from 171 patients during a six-month period coinciding with large-scale construction work beside the hospital. Most patients presented with bacteraemia (146/171; 85.4%) with 46/171 (26.9%) requiring extended treatment courses with vancomycin or other interventions. Sampling confirmed extensive airborne dispersal inside the hospital, including isolation rooms and air-conditioned wards. Hospital linen was heavily contaminated [7403 cfu/cm(2); 95% confidence interval (CI): 6349-8457; for 30 towels sampled], encouraged by inappropriate storage in airtight plastic bags (4437 cfu/cm(2); CI: 3125-5750) compared with storage in porous canvas bags (166 cfu/cm(2); CI: 76-256; P < 0.001). Interventions introduced included revision of laundry practices, transport and storage of hospital linen and towels; bleach-based environmental cleaning; and upgrading of ventilation systems throughout the hospital. Clinical case numbers returned to baseline levels within three months, only to rise again following relaxation of laundry practices. CONCLUSIONS: Construction work beside this Singapore hospital encouraged heavy contamination of air and environment with Bacillus spp., assumed to be responsible for the outbreak described. Failure to maintain revised laundry practices allowed resurgence of clinical cases, particularly among immunocompromised patients.

Isolation of the first three cases of Clostridium difficile polymerase chain reaction ribotype 027 in Singapore.

INTRODUCTION: The incidence of Clostridium (C.) difficile infection (CDI) was on the rise from 2001 to 2006 in Singapore. Recent unpublished data suggests that its incidence had remained stable or decreased in most local public hospitals between 2006 and 2010. It is, however, not known if the polymerase chain reaction (PCR) ribotype 027 strains have been circulating, although reports suggest that this strain is emerging in Asia, with the first cases reported from Japan in 2007, as well as in Hong Kong and Australia in 2009. We initiated a culture-based surveillance to detect this epidemic strain in Singapore. METHODS: From September 2008 to December 2009, all non-duplicate toxin-positive stool samples from the three largest public hospitals in Singapore were collected for culture and further analysis. RESULTS: Out of the 366 samples collected, 272 viable isolates were cultured. Of these, 240 tested toxin-positive and ten tested positive for the binary toxin gene; 35 different PCR ribotypes were found. Three isolates that tested positive for binary toxin contained the same PCR ribotyping pattern as the C. difficile 027 control strain. All three had the 18-bp deletion and single nucleotide tcdC deletion at position 117. Susceptibility testing was performed, demonstrating susceptibility to erythromycin and moxifloxacin. CONCLUSION: We report the first three isolates of C. difficile 027 from Singapore. However, their susceptibility patterns are more consistent with the historical 027 strains. Rising CDI incidence may not be associated with the emergence of the epidemic 027 strain at this time.

Increased detection in Australia and Singapore of a novel influenza A(H1N1)2009 variant with reduced oseltamivir and zanamivir sensitivity due to a S247N neuraminidase mutation.

A novel influenza A(H1N1)2009 variant with mildly reduced oseltamivir and zanamivir sensitivity has been detected in more than 10% of community specimens in Singapore and more than 30% of samples from northern Australia during the early months of 2011. The variant, which has also been detected in other regions of the Asia-Pacific, contains a S247N neuraminidase mutation. When combined with the H275Y mutation, as detected in an oseltamivir-treated patient, the dual S247N+H275Y mutant had extremely high oseltamivir resistance.

Development of multiplex PCR assays based on the 16S-23S rRNA internal transcribed spacer for the detection of clinically relevant nontuberculous mycobacteria.

AIMS: To accelerate the identification and differentiation of clinically relevant nontuberculous mycobacteria (NTM) with two sets of multiplex PCR (mPCR) targeting the 16S-23S rRNA internal transcribed spacer (ITS) region for timely patient management. METHODS AND RESULTS: Two mPCR assays were developed: Slow-Growers (SG) mPCR was used for the detection of slow-growing mycobacteria, which included Mycobacterium avium complex, Mycobacterium kansasii, Mycobacterium gordonae and Mycobacterium xenopi whilst the other mPCR assay labelled as Fast-Growers (FG) mPCR was used for the detection of Mycobacterium fortuitum complex, Mycobacterium abscessus and Mycobacterium chelonae. In these assays, a common forward primer based on a conserved section of the 16S rRNA region was used in conjunction with species-specific reverse primers. The mPCRs were tested against 247 clinical mycobacterial isolates and demonstrated 100% specificity and sensitivity. Identification of the mycobacterial species was also validated by DNA sequencing of the 16S-23S ITS region and when further confirmation was needed, hsp65 sequencing was performed. CONCLUSIONS: The mPCR assays could be a potentially useful diagnostic tool for the rapid and accurate identification of clinically relevant NTM. SIGNIFICANCE AND IMPACT OF THE STUDY: In this study, we looked at the frequency of hospital isolated NTM over the last 5 years (2005-2010), and an mPCR targeting the ITS region was developed for NTM species that appeared to be more prevalent in the context of Singapore.