Dominant Carbapenemase-Encoding Plasmids in Clinical Enterobacterales Isolates and Hypervirulent Klebsiella pneumoniae,Singapore

Dissemination of carbapenemase-encoding plasmids by horizontal gene transfer in multidrug-resistant bacteria is the major driver of rising carbapenem-resistance, but the conjugative mechanics and evolution of clinically relevant plasmids are not yet clear. We performed whole-genome sequencing on 1,215 clinical Enterobacterales isolates collected in Singapore during 2010–2015. We identified 1,126 carbapenemase-encoding plasmids and discovered pKPC2 is becoming the dominant plasmid in Singapore, overtaking an earlier dominant plasmid, pNDM1. pKPC2 frequently conjugates with many Enterobacterales species, including hypervirulent Klebsiella pneumoniae, and maintains stability in vitro without selection pressure and minimal adaptive sequence changes. Furthermore, capsule and decreasing taxonomic relatedness between donor and recipient pairs are greater conjugation barriers for pNDM1 than pKPC2. The low fitness costs pKPC2 exerts in Enterobacterales species indicate previously undetected carriage selection in other ecological settings. The ease of conjugation and stability of pKPC2 in hypervirulent K. pneumoniae could fuel spread into the community.     

Factors of Never Screened with Faecal Occult Blood Test in Public Primary Care Facilities

Background: Colorectal cancer (CRC) is still a major public health threat. In the effort to reduce CRC incidence and mortality, faecal occult blood test (FOBT) is currently the screening tools used for early detection of CRC. However, the uptake of FOBT screening is less than promising. This study aims to identify the prevalence and predictors of Never Screened with FOBT (NS-FOBT). Methods: A cross sectional study was conducted in five health clinics under Kota Kinabalu district, Sabah, Malaysia Borneo involving 162 attendees with age of 50 years old and above. A validated self-administered questionnaire was used to collect the data. Multiple logistic regression analysis was used to determine the predictors of NS-FOBT. Results: The prevalence of NS-FOBT was 85.8% (n=139). Important predictors of NS-FOBT were age (aOR: 0.922; 95% CI: 0.855, 0.995; p=0.035), Bumiputera ethnicity (vs Non Bumiputera; aOR: 4.285; 95% CI: 1.384, 13.263; p=0.012), knowledge score (aOR: 0.921; 95% CI: 0.856, 0.99; p=0.027), and attitude score (aOR: 0.801; 95% CI: 0.702, 0.913; p=0.001). Conclusion: There is high prevalence of NS-FOBT. Age, ethnicity, knowledge, and attitude were important predictors of NS-FOBT. Strategies are needed to improve FOBT screening rate among the public. Socio-culturally tailored health promotion strategies as well as strengthening the communication, collaboration, and education to enhance the role of family physician is vital in improving the CRC prevention and care.     

Investigation of bone invasion and underlying mechanisms of oral cancer using a cell line-derived xenograft model

The cancer stroma regulates bone invasion in oral squamous cell carcinoma (OSCC). However, data on normal stroma are limited. In the present study, the effects of gingival and periodontal ligament tissue-derived stromal cells (G-SCs and P-SCs, respectively) and human dermal fibroblasts (HDFs) on bone resorption and osteoclast activation were assessed using hematoxylin and eosin and tartrate-resistant acid phosphatase staining in a cell line-derived xenograft model. The results demonstrated that G-SCs promoted bone invasion and osteoclast activation and inhibited osteoclast proliferation following crosstalk with the human OSCC HSC-3 cell line, whereas P-SCs inhibited bone resorption and promoted osteoclast proliferation in vitro but had a minimal effect on osteoclast activation both in vitro and in vivo following crosstalk with HSC-3 cells. Furthermore, the effects of G-SCs, P-SCs and HDFs on protein expression levels of matrix metalloproteinase (MMP)-9, membrane type 1 MMP (MT1-MMP), Snail, parathyroid hormone-related peptide (PTHrP) and receptor activator of NF-κB ligand (RANKL) in HSC-3 cells in OSCC bone invasion regions were assessed using immunohistochemistry. The results demonstrated that G-SCs had a more prominent effect on the expression of MMP-9, MT1-MMP, Snail, PTHrP, and RANKL, whereas P-SCs only promoted RANKL and PTHrP expression and exerted a minimal effect on MMP-9, MT1-MMP and Snail expression. The potential genes underlying the differential effects of G-SCs and P-SCs on bone invasion in OSCC were evaluated using a microarray, which indicated that cyclin-dependent kinase 1, insulin, aurora kinase A, cyclin B1 and DNA topoisomerase II alpha underlaid these differential effects. Therefore, these results demonstrated that G-SCs promoted bone invasion in OSCC by activating osteoclasts on the bone surface, whereas P-SCs exerted an inhibitory effect. These findings could indicate a potential regulatory mechanism for bone invasion in OSCC.     

Addressing extreme size mismatch in pediatric intestinal transplantation: Outcomes of intestinal length reduction

Background

Bench liver reduction, with or without intestinal length reduction (LR) (coupled with delayed closure and abdominal wall prostheses), has been a strategy adopted by our program for small children due to the limited availability of size-matched donors. This report describes the short, medium, and long-term outcomes of this graft reduction strategy.

Methods

A single-center, retrospective analysis of children that underwent intestinal transplantation (April 1993 to December 2020) was performed. Patients were grouped according to whether they received an intestinal graft of full length (FL) or following LR.

Results

Overall, 105 intestinal transplants were performed. The LR group (n = 10) was younger (14.5 months vs. 40.0 months, p = .012) and smaller (8.7 kg vs. 13.0 kg, p = .032) compared to the FL group (n = 95). Similar abdominal closure rates were achieved after LR, without any increase in abdominal compartment syndrome (1/10 vs. 7/95, p = .806). The 90-day graft and patient survival were similar (9/10, 90% vs. 83/95, 86%; p = .810). Medium and long-term graft survival at 1 year (8/10, 80% vs. 65/90, 71%; p = .599), and 5 years (5/10, 50% vs. 42/84, 50%; p = 1.00) was similar.

Conclusion

LR of intestinal grafts appears to be a safe strategy for infants and small children requiring intestinal transplantation. This technique should be considered in the situation of significant size mismatch of intestine containing grafts.     

Sexual activity satisfaction in symptomatic hip osteoarthritis patients: A cross-sectional,national web-based study

Aim

Despite high-interest rates in sex in people with hip osteoarthritis (OA), clinicians tend not to address sexual issues, especially in older adults. The objective of this study is to evaluate sexual activity and factors associated with sexual activity satisfaction in people with symptomatic hip OA.

Methods

A cross-sectional study was conducted among 252 participants with symptomatic hip OA in Australia. Quality of sex life was assessed using the online composite of sexual activities and positions questionnaires. A Poisson model with robust variance was used to calculate the prevalence ratio (PR). Factors that showed a univariate association with sexual satisfaction were then included in a multivariable model. PR with corresponding 95% confidence intervals (CI) are reported.

Results

Among the 282 participants registered on the study website, 252 met the inclusion criteria, and 60.3% (152/252) completed the sexual activity questionnaires. Hip OA interfered with sexual activity in 70.0% of the participants. High confidence in completing sexual activity (PR: 0.53, 95% CI: 0.36 to 0.77) was associated with an increased prevalence ratio of sexual satisfaction. High anxiety, depression or stress during sexual activity (PR: 1.33, 95% CI: 1.10 to 1.60) was associated with an increased prevalence ratio of sexual dissatisfaction after adjusting for hip pain level and perceived partner's orgasm.

Conclusion

Although a large proportion of people with hip OA remain sexually active, a substantial proportion of persons are dissatisfied with their sexual activity. Hip OA interfered with sexual activity in most participants. Psychological factors were found to be associated with sexual activity satisfaction.     

Research gaps and opportunities in autoimmune hepatitis—Results of the international autoimmune hepatitis group research workshop 2022

Autoimmune hepatitis (AIH) is a rare autoimmune liver disease that is characterised by a chronic inflammatory immune reaction directed against hepatocytes. The disease results in a substantial reduction in quality of life and potentially leads to liver-related complications or death. The International Autoimmune Hepatitis Group (IAIHG) initiated a series of research workshops to uncover the scientific gaps and opportunities in AIH. This review summarises the results of the latest workshop in Maastricht in 2022 and reviews the current challenges in adult AIH, particularly in relation to four important aspects of AIH: diagnostics; new immunomodulatory therapies; clinical trial design; and unmet clinical needs. This review also summarises the progress made since the AIH workshop in 2017. Patients and patient representatives were actively involved in the parallel working groups alongside clinicians and researchers. Despite 40 years of experience with diagnosing and treating AIH, false diagnoses occur and treatment is still based on nonselective immunosuppression. In addition to the need for more specific diagnostic tests, prognostic markers and tailor-based treatments, a major unmet clinical need was identified in areas of care delivery and health-related quality of life.     

Inflammatory ultrasound features as prognostic factors of pain and functional outcomes following intra-articular platelet-rich plasma in knee osteoarthritis

Aim

To explore inflammatory ultrasound predictors of improvements in pain and function over 2, 6, and 12 months following administration of intra-articular platelet-rich plasma (PRP) in knee osteoarthritis (OA).

Method

Patients with painful mild–moderate radiographic knee OA from a subset of the RESTORE RCT underwent ultrasound assessment according to the standardized OMERACT scanning protocol to detect inflammatory features such as synovitis, synovial hypertrophy, and effusion with power Doppler. The study knee was treated with 3 once-weekly PRP injections obtained after centrifugation at 1500 g for 5 min. Numerical Rating Score (NRS), Intermittent and Constant Osteoarthritis Pain (ICOAP) questionnaire, and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) function sub-score were used to measure pain and functional severity. Separate linear regression models were performed to determine whether baseline ultrasound-detected features of inflammation predicted the improvement in pain and function following PRP injection in both unadjusted and adjusted models for confounders.

Results

Forty-four participants were included, with 25 (56.8%) being female. In an unadjusted model, higher OMERACT scores for inflammatory features such as global synovitis and/or effusion were significantly associated with greater improvement in all outcomes measured at 2 months but not at 6 and 12 months for pain measures. Only global synovitis showed significant association with functional improvement at 2 and 12 months. Similar findings were observed in the adjusted model.

Conclusion

Ultrasound indices of knee inflammation predicted short-term improvements in pain severity and both short- and longer-term improvements in function following intra-articular PRP injection.