Reducing Delays in MRIs under Sedation and General Anesthesia Using Quality Improvement Tools.

OBJECTIVE: Develop structured, quality improvement (QI) interventions to achieve a 15%-point reduction in MRIs performed under sedation or general anesthesia (GA) delayed over 15 minutes within a 6-month period. METHODS: A prospective audit of MRIs under sedation or GA from January 2022 to June 2023 was conducted. A multidisciplinary team performed process mapping and root cause analysis for delays. Interventions were developed and implemented over four 'Plan, Do, Study, Act' (PDSA) cycles, targeting workflow standardization, pre-admission patient counselling, reinforcing adherence to scheduled scan times and written consent respectively. Delay times (compared with Kruskal-Wallis and Dunn's tests), delays over 15 minutes and delays of 60 or more minutes at baseline and after each PDSA cycle were recorded. RESULTS: 627 MRIs under sedation or GA were analyzed, comprising 443 at baseline and 184 post-implementation. 556/627 (88.7%) scans were performed under sedation, 22/627 (3.5%) under monitored anesthesia care and 49/627 (7.8%) under GA. At baseline, 71.6% (317/443) scans were delayed over 15 minutes and 28.2% (125/443) scans by 60 or more minutes, with a median delay of 30 minutes. Post-implementation, there was a 34.7%-point reduction in scans delayed over 15 minutes, 17.5%-point reduction in scans delayed by 60 or more minutes and reduced median delay time by 15 minutes (p <0.001). DISCUSSION: Structured interventions significantly reduced delays in MRIs under sedation and GA, potentially improving outcomes for both patients and providers. Key factors included a diversity of perspectives in the study team, continued stakeholder engagement and structured QI tools including PDSA cycles.

Immune microenvironment of basal cell carcinoma and tumor regression following combined PD-1/LAG-3 blockade.

Systemic treatment options for patients with locally advanced or metastatic basal cell carcinoma (BCC) are limited, particularly when tumors are refractory to anti-programmed cell death protein-1 (PD-1). A better understanding of immune checkpoint expression within the BCC tumor microenvironment may inform combinatorial treatment strategies to optimize response rates. CD3, PD-1, programmed death ligand-1 (PD-L1), lymphocyte activation gene 3 (LAG-3), and T-cell immunoglobulin domain and mucin domain 3 (TIM-3)+ cell densities within the tumor microenvironment of 34 archival, histologically aggressive BCCs were assessed. Tumor infiltrating lymphocyte (TIL) expression of PD-1, PD-L1, and LAG-3, and to a lesser degree TIM-3, correlated with increasing CD3+ T-cell densities (Pearson's r=0.89, 0.72, 0.87, and 0.63, respectively). 100% of BCCs (34/34) demonstrated LAG-3 and PD-1 expression in >1% TIL; and the correlation between PD-1 and LAG-3 densities was high (Pearson's r=0.89). LAG-3 was expressed at ~50% of the level of PD-1. Additionally, we present a patient with locally-advanced BCC who experienced stable disease during and after 45 weeks of first-line anti-PD-1 (nivolumab), followed by a partial response after the addition of anti-LAG-3 (relatlimab). Longitudinal biopsies throughout the treatment course showed a graduated increase in LAG-3 expression after anti-PD-1 therapy, lending support for coordinated immunosuppression and suggesting LAG-3 as a co-target for combination therapy to augment the clinical impact of anti-PD-(L)1.

Falsarthrobacter nasiphocae periprosthetic joint infection.

We report the isolation of a rare Gram-positive coccobacillary bacterium from synovial fluids of a patient with periprosthetic joint infection on three occasions over an 8-month period. As routine microbiological methods were not able to identify the isolate definitely, sequence analyses of the bacterial 16S ribosomal RNA gene and whole genome were performed. Analysis of the bacterial 16S ribosomal RNA gene showed the highest similarity (98.1%) with that of Falsarthrobacter (previously known as Arthrobacter) nasiphocae, which was first isolated from the nasal cavities of common seals (Phoca vitulina). The genome size of the strain (designated as UM1) is 2.4 Mb. With a high G+C content (70.4 mol%), strain UM1 is phylogenetically most closely related to F. nasiphocae based on whole genome analysis. Strain UM1 was susceptible to vancomycin, linezolid, trimethoprim-sulfamethoxazole, doxycycline, and intermediate to penicillin and ciprofloxacin. Ceftriaxone resistance was noted. The patient who was also on hemodialysis for his end stage kidney disease died approximately 3 weeks following implant removal and fusion with an external fixator. This study describes the first isolation of F. nasiphocae from human clinical samples. The use of emerging technologies has supported more definitive etiological diagnosis associated with rarely encountered organisms in periprosthetic joint infection.

A kidney diagnostic's impact on physician decision-making in diabetic kidney disease.

OBJECTIVES: Estimated glomerular filtration rate (eGFR) and albuminuria, the current standard-of-care tests that predict risk of kidney function decline in early-stage diabetic kidney disease (DKD), are only modestly useful. We evaluated the decision-making impact of an artificial intelligence-enabled prognostic test, KidneyIntelX, in the management of DKD by primary care physicians (PCPs). STUDY DESIGN: This was a prospective web-based survey administered among PCPs in the United States. METHODS: We used conjoint analysis with multivariable logit models to estimate PCP preferences. The survey included hypothetical patient profiles with 6 attributes: albuminuria, eGFR, age, blood pressure (BP), hemoglobin A1c (HbA1c), and KidneyIntelX result. Each PCP viewed 8 patient profiles randomly selected from 42 unique profiles having 1 level from each attribute. For each patient, PCPs were asked to indicate whether they would prescribe a sodium-glucose cotransporter-2 (SGLT2) inhibitor, increase angiotensin receptor blocker (ARB) dose, and/or refer to a nephrologist. RESULTS: A total of 401 PCPs completed the survey (response rate, 8.8%). The relative importance of the top 2 attributes for each decision were HbA1c (52%) and KidneyIntelX result (23%) for prescribing SGLT2 inhibitors, BP (62%) and KidneyIntelX result (13%) for increasing ARB dose, and eGFR (42%) and KidneyIntelX result (27%) for nephrologist referral. A high-risk KidneyIntelX result was associated with significantly higher odds of PCPs prescribing SGLT2 inhibitors (odds ratio [OR], 1.64; 95% CI, 1.29-2.08), increasing ARB dose (OR, 1.49; 95% CI, 1.17-1.89), and referring to a nephrologist (OR, 2.47; 95% CI, 1.99-3.08) compared with no test. CONCLUSIONS: The KidneyIntelX test had greater relative importance than albuminuria and eGFR to PCPs in making treatment decisions and was second only to eGFR for nephrologist referrals. Because of its significant impact on decision-making, KidneyIntelX has high clinical utility in DKD management.

Dearth of influenza among older adults admitted with respiratory symptoms in Malaysia during the coronavirus disease 2019 pandemic in 2021.

Introduction: Influenza is a common respiratory virus which leads to over 400,000 annual deaths globally. Mortality from influenza is highest among those aged 75 years and over living in Africa and Southeast Asia. Objective: To determine the burden of influenza among older adults presenting to public hospitals with severe acute respiratory infection (SARI) during the coronavirus disease 2019 (COVID-19) pandemic. Methods: This multi-center, prospective, observational study recruited individuals aged 65 years and over who presented to four Malaysian hospitals with SARI from 1 January to 31 December 2021. Those with prior confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection were excluded. SARS-CoV-2 was detected through real-time polymerase chain reaction (PCR) with routine diagnostic kits. Influenza A, influenza B and respiratory syncytial virus (RSV) viruses were detected with Xpress Flu/RSV kits using the GeneXpert rapid real-time PCR system (Cepheid, USA). Results: Samples were obtained from 512 participants, comprising 296 (57.8%) men and 216 (42.2%) women, with a mean age (SD) of 74.0 (7.1) years. Inpatient death occurred in 48 (9.6%) individuals. Significant differences existed in age, ethnicity, and comorbidities across study sites. One (0.2%) case of influenza A, two (0.4%) cases of RSV and 63 (12.5%) cases of SARS-CoV-2 infection were detected over the 1-year period. Cases of COVID-19 mirrored national trends derived from open source data, while the dearth of influenza cases mirrored national and global Flunet figures. Conclusion: Our observational study conducted during the COVID-19 pandemic detected only one case of influenza, alongside a high SARS-CoV-2 positivity rate. The poor uptake of influenza vaccination nationally, worsened by the recent pandemic restrictions, could lead to waning immunity from the absence of seasonal exposure. Potentially deadly outbreaks may then occur when lockdown and infection control measures are eventually removed.

Integrating Photovoice and Citizen Science: The Our Voice Initiative in Practice.

Community engagement methods like photovoice have allowed researchers to gather and incorporate the experiences and perspectives of community members in their work but have at times faced challenges regarding systematization, accessibility, and scalability. This practice note describes the Our Voice initiative, one example of a community-based participatory research framework that aims to build on photovoice theories and best practices and address these challenges by incorporating the use of a mobile app as well as elements of participatory action-based citizen science to support community-driven data collection, analysis, and advocacy. We explore the application of the Our Voice method and evaluation of multilevel participant and community outcomes across three different Bay Area, California, communities. In doing so, we hope to provide a potential example for practitioners of other community-based participatory research and photovoice-based models to draw from when working with diverse communities to integrate local perspectives and insights in the generation and implementation of sustainable community health improvements.

Correction: Development of a reverse transcription recombinase polymerase amplification assay for rapid and direct visual detection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).

[This corrects the article DOI: 10.1371/journal.pone.0245164.].

Development of a reverse transcription recombinase polymerase amplification assay for rapid and direct visual detection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).

Rapid diagnosis is an important intervention in managing the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) outbreak. Real time reverse transcription polymerase chain reaction (RT-qPCR) remains the primary means for diagnosing the new virus strain but it is time consuming and costly. Recombinase polymerase amplification (RPA) is an isothermal amplification assay that does not require a PCR machine. It is an affordable, rapid, and simple assay. In this study, we developed and optimized a sensitive reverse transcription (RT)-RPA assay for the rapid detection of SARS-CoV-2 using SYBR Green I and/or lateral flow (LF) strip. The analytical sensitivity and specificity of the RT-RPA assay were tested by using 10-fold serial diluted synthetic RNA and genomic RNA of similar viruses, respectively. Clinical sensitivity and specificity of the RT-RPA assay were carried out using 78 positive and 35 negative nasopharyngeal samples. The detection limit of both RPA and RT-qPCR assays was 7.659 and 5 copies/µL RNA, respectively with no cross reactivity with other viruses. The clinical sensitivity and specificity of RT-RPA were 98% and 100%, respectively. Our study showed that RT-RPA represents a viable alternative to RT-qPCR for the detection of SARS-CoV-2, especially in areas with limited infrastructure.

SARS-CoV-2 lineage B.6 was the major contributor to early pandemic transmission in Malaysia.

Malaysia had 10,219 confirmed cases of COVID-19 as of September 20, 2020. About 33% were associated with a Tablighi Jamaat religious mass gathering held in Kuala Lumpur between February 27 and March 3, 2020, which drove community transmission during Malaysia's second wave. We analysed genome sequences of SARS-CoV-2 from Malaysia to better understand the molecular epidemiology and spread. We obtained 58 SARS-CoV-2 whole genome sequences from patients in Kuala Lumpur and performed phylogenetic analyses on these and a further 57 Malaysian sequences available in the GISAID database. Nine different SARS-CoV-2 lineages (A, B, B.1, B.1.1, B.1.1.1, B.1.36, B.2, B.3 and B.6) were detected in Malaysia. The B.6 lineage was first reported a week after the Tablighi mass gathering and became predominant (65.2%) despite being relatively rare (1.4%) globally. Direct epidemiological links between lineage B.6 viruses and the mass gathering were identified. Increases in reported total cases, Tablighi-associated cases, and community-acquired B.6 lineage strains were temporally linked. Non-B.6 lineages were mainly travel-associated and showed limited onward transmission. There were also temporally correlated increases in B.6 sequences in other Southeast Asian countries, India and Australia, linked to participants returning from this event. Over 95% of global B.6 sequences originated from Asia Pacific. We also report a nsp3-C6310A substitution found in 47.3% of global B.6 sequences which was associated with reduced sensitivity using a commercial diagnostic real-time PCR assay. Lineage B.6 became the predominant cause of community transmission in Malaysia after likely introduction during a religious mass gathering. This event also contributed to spikes of lineage B.6 in other countries in the Asia-Pacific. Mass gatherings can be significant causes of local and global spread of COVID-19. Shared genomic surveillance can be used to identify SARS-CoV-2 transmission chains to aid prevention and control, and to monitor diagnostic molecular assays. Clinical Trial Registration: COVID-19 paper.

Complete Genome Sequences of SARS-CoV-2 Strains Detected in Malaysia.

We sequenced four severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes from Malaysia during the second wave of infection and found unique mutations which suggest local evolution. Circulating Malaysian strains represent introductions from different countries, particularly during the first wave of infection. Genome sequencing is important for understanding local epidemiology.

Genome Analysis of the First Extensively Drug-Resistant (XDR) Mycobacterium tuberculosis in Malaysia Provides Insights into the Genetic Basis of Its Biology and Drug Resistance.

The outbreak of extensively drug-resistant tuberculosis (XDR-TB) has become an increasing problem in many TB-burdened countries. The underlying drug resistance mechanisms, including the genetic variation favored by selective pressure in the resistant population, are partially understood. Recently, the first case of XDR-TB was reported in Malaysia. However, the detailed genotype family and mechanisms of the formation of multiple drugs resistance are unknown. We sequenced the whole genome of the UM 1072388579 strain with a 2-kb insert-size library and combined with that from previously sequenced 500-bp-insert paired-end reads to produce an improved sequence with maximal sequencing coverage across the genome. In silico spoligotyping and phylogenetic analyses demonstrated that UM 1072388579 strain belongs to an ancestral-like, non-Beijing clade of East Asia lineage. This is supported by the presence of a number of lineage-specific markers, including fadD28, embA, nuoD and pks7. Polymorphism analysis showed that the drug-susceptibility profile is correlated with the pattern of resistance mutations. Mutations in drug-efflux pumps and the cell wall biogenesis pathway such as mmpL, pks and fadD genes may play an important role in survival and adaptation of this strain to its surrounding environment. In this work, fifty-seven putative promoter SNPs were identified. Among them, we identified a novel SNP located at -4 T allele of TetR/acrR promoter as an informative marker to recognize strains of East Asian lineage. Our work indicates that the UM 1072388579 harbors both classical and uncommon SNPs that allow it to escape from inhibition by many antibiotics. This study provides a strong foundation to dissect the biology and underlying resistance mechanisms of the first reported XDR M. tuberculosis in Malaysia.

First report of cervicofacial lymphadenitis due to Mycobacterium haemophilum in an immunocompromised adult patient.

We report the first case of an immunocompromised adult patient presenting with cervicofacial lymphadenitis due to Mycobacterium haemophilum, confirmed using hsp65 gene sequencing and line-probe assays. In resource-limited settings, especially in developing countries, appropriate culture methods and rapid molecular diagnostic tools such as hsp65 gene sequencing for identification of this organism may not be readily available. This may cause M. haemophilum infections to go unrecognised or lead to delays in diagnosis. Lack of heightened awareness about the potential for this mycobacterial species to cause infections may also contribute to possible underestimation of M. haemophilum cases in the developing world.

Diffusion-weighted imaging properties of uterine fibroids pre- and post-uterine fibroid embolisation.

OBJECTIVE: To determine the change in apparent diffusion coefficient (ADC) of uterine fibroids following uterine fibroid embolisation (UFE), and if the ADC change correlates with either volume loss or degree of contrast enhancement post-UFE. MATERIALS AND METHODS: This study was approved by our institutional review board with waiver of consent. The pelvic MRI examinations, including diffusion-weighted MRI (DWI) using 4 b-values, of 50 consecutive patients prior to and 6 months post-UFE were analyzed. The volume, ADC and amount of enhancement were calculated for each fibroid both pre- and post-UFE. The percent residual enhancement for each fibroid was categorized as either: no (0-1%) residual enhancement or residual (>1%) enhancement. Statistical analysis compared ADC, enhancement and volume for each fibroid pre- and post-UFE using paired t-tests and Pearson correlation coefficients. RESULTS: The mean ADC of all (n=88) fibroids pre-UFE was 1.30±0.20×10(-3)mm(2)/s, and increased to 1.68±0.24×10(-3)mm(2)/s post-UFE (p<0.0001). Lower pre-UFE ADC correlated with greater ADC change post-UFE (r=-0.50; p<0.0001). There was no correlation between ADC change and volume change post-UFE (r=0.07; p=0.59). However, fibroids with no residual enhancement post-UFE had larger ADC change than those with residual enhancement (p=0.003). CONCLUSION: The ADC of fibroids rises post-UFE. ADC change post-UFE is associated with the degree of loss of enhancement and may therefore be valuable in predicting response to treatment in pre-procedural counseling.

Identification of Mycobacterium species following growth detection with the BACTEC MGIT 960 system by DNA line probe assay.

BACKGROUND: The tuberculosis and infections caused by nontuberculous mycobacterial (NTM) species are increasing in patients presented with respiratory illness, and it is crucial to document the epidemiology of these infections. OBJECTIVES: To study the mycobacterial species and in vitro drug susceptibility trends of Mycobacterium tuberculosis found in the respiratory specimens. MATERIALS AND METHODS: A prospective descriptive study from July 2009 to December 2012. The BACTEC MGIT system tubes with growth were used in the study. GenoType Mycobacterium (Hain Diagnostika, Nehren, Germany) assays were used to identify the mycobacteria. The drug susceptibility testing was performed by the MGIT 960 system. RESULTS: A total of 1745 MGIT 960 system positive tubes were included. M. tuberculosis complex (MTC) constituted 67.45% of the yield isolated, 30.83% were nontuberculous mycobacterial species, 0.17% were Mycobacterium bovis BCG and 1.55% were not interpretable to species levels. Mycobacterium fortuitum (45.71%), Mycobacterium abscessus (26.21%) and Mycobacterium intracellulare (10.41%) were major NTM identified. The drug susceptibility study showed that 6.88% (81/1177) of MTC were drug-resistant TB, 56 isolates were resistant to one of the first-line anti-TB drugs, 25 isolates were found to be resistant to 2 or more first-line anti-TB drugs, of which 19 (20.46%) were MDR-TB and one of the isolates in the year 2011 was confirmed XDR-TB. CONCLUSION: M. tuberculosis, M. fortuitum, M. abscessus and M. intracellulare were major mycobacterial species detected in the respiratory samples. The drug susceptibility testing showed that the majority of MTC were sensitive to first-line anti-TB drugs.

Draft Genome Sequence of the First Isolate of Extensively Drug-Resistant (XDR) Mycobacterium tuberculosis in Malaysia.

The emergence of the global threat of extensively drug-resistant (XDR) Mycobacterium tuberculosis reveals weaknesses in tuberculosis management and diagnostic services. We report the draft genome sequence of the first extensively drug-resistant Mycobacterium tuberculosis strain isolated in Malaysia. The sequence was also compared against a reference strain to elucidate the polymorphism that is related to their extensive resistance.

Papillary lesions of the breast: MRI, ultrasound, and mammographic appearances.

OBJECTIVE: The purpose of this article is to describe the different imaging appearances of benign and malignant papillary lesions of the breast as well as to point out potential errors of interpretation that can lead to misdiagnosis. CONCLUSION: There is a wide spectrum of appearances of papillary lesions of the breast on MRI, ultrasound, and mammography. This variable appearance of papillary lesions makes differentiation of benign from malignant pathologies difficult on imaging, and tissue sampling is usually warranted.

Nuclear shape, growth and integrity in the closed mitosis of fission yeast depend on the Ran-GTPase system, the spindle pole body and the endoplasmic reticulum.

The double lipid bilayer of the nuclear envelope (NE) remains intact during closed mitosis. In the fission yeast Schizosaccharomyces pombe, the intranuclear mitotic spindle has envelope-embedded spindle pole bodies (SPB) at its ends. As the spindle elongates and the nucleus divides symmetrically, nuclear volume remains constant but nuclear area rapidly increases by 26%. When Ran-GTPase function is compromised in S. pombe, nuclear division is strikingly asymmetrical and the newly synthesized SPB is preferentially associated with the smaller nucleus, indicative of a Ran-dependent SPB defect that interferes with symmetrical nuclear division. A second defect, which specifically influences the NE, results in breakage of the NE upon spindle elongation. This defect, but not asymmetric nuclear division, is partially rescued by slowing spindle elongation, stimulating endoplasmic reticulum (ER) proliferation or changing conformation of the ER membrane. We propose that redistribution of lipid within the ER-NE network is crucial for mitosis-specific NE changes in both open and closed mitosis.

Molecular differentiation and antifungal susceptibilities of Candida parapsilosis isolated from patients with bloodstream infections.

The genetic heterogeneity and antifungal susceptibility patterns of Candida parapsilosis isolated from blood cultures of patients were investigated in this study. Randomly amplified polymorphic DNA (RAPD) analysis generated 5 unique profiles from 42 isolates. Based on the major DNA fragments of the RAPD profiles, the isolates were identified as RAPD type P1 (29 isolates), P2 (6 isolates), P3 (4 isolates), P4 (2 isolates) and P5 (1 isolate). Sequence analysis of the internal transcribed spacer (ITS) gene of the isolates identified RAPD type P1 as C. parapsilosis, P2 and P3 as Candida orthopsilosis, P4 as Candida metapsilosis, and P5 as Lodderomyces elongisporus. Nucleotide variations in ITS gene sequences of C. orthopsilosis and C. metapsilosis were detected. Antifungal susceptibility testing using Etests showed that all isolates tested in this study were susceptible to amphotericin B, fluconazole, ketoconazole, itraconazole and voriconazole. C. parapsilosis isolates exhibited higher MIC(50) values than those of C. orthopsilosis for all of the drugs tested in this study; however, no significant difference in the MICs for these two Candida species was observed. The fact that C. orthopsilosis and C. metapsilosis were responsible for 23.8 and 4.8 % of the cases attributed to C. parapsilosis bloodstream infections, respectively, indicates the clinical relevance of these newly described yeasts. Further investigations of the ecological niche, mode of transmission and virulence of these species are thus essential.

Does the use of nizatidine, as a pro-kinetic agent, improve gastric emptying in patients post-oesophagectomy?

PURPOSE: Delayed gastric emptying following oesophagectomy is common and can often lead to weight loss, malnutrition and a poor quality of life. Animal models have shown that nizatidine, a histamine H2-receptor antagonist, has pro-kinetic properties and can accelerate gastric emptying. Patients post-oesophagectomy require long-term acid suppression medication; if nizatidine can improve gastric emptying, it can be adopted for its dual pharmacological actions. METHODOLOGY: Twenty consecutive patients were prospectively enrolled in this trial following oesophagectomy. All patients were more than 6 months post-surgery and had no evidence of recurrent cancer. A baseline nuclear medicine scan following a radiolabelled meal was conducted and then repeated after 1 week of nizatidine (150 mg bd) treatment. Quality of life and eating comfort data were collected. RESULTS: Oesophagectomy causes a significant delay in gastric emptying. Early satiety (80%) and reflux (65%) were the most common post-operative complaints. The percentage of food remaining in the stomach at 60 min post-meal was significantly more than normal values in both the pre- and post-nizatidine studies. There is no advantage in using nizatidine as a pro-kinetic agent. CONCLUSIONS: Impaired gastric emptying post-surgery causes a change in eating habits. Patients in this study did not lose a significant amount of weight despite all indicating worse eating comfort. Patients required more regular meals or snacks throughout the day and avoid foods that are difficult to swallow. It is likely that gastric motility only plays a small role in the emptying process and gravity combined with appropriate drainage procedures (pyloroplasty/pyloromyotomy) at the time of surgery are more important.