FARGO-360: a multi-disciplinary survey of practice and perspectives on provision of care for patients with frailty presenting with gynecological cancers in the UK and Ireland.

OBJECTIVES: Frailty has been associated with worse cancer-related outcomes for people with gynecological cancers. However, the lack of clear guidance on how to assess and modify frailty prior to instigating active treatments has the potential to lead to large variations in practice and outcomes. This study aimed to evaluate current practice and perspectives of healthcare practitioners on the provision of care for patients with frailty and a gynecological cancer. METHODS: Data were collected via a questionnaire-based survey distributed by the Audit and Research in Gynecological Oncology (ARGO) collaborative to healthcare professionals who identified as working with patients with gynecological malignancies in the United Kingdom (UK) or Ireland. Study data were collected using REDCap software hosted at the University of Manchester. Responses were collected over a 16 week period between January and April 2021. RESULTS: A total of 206 healthcare professionals (30 anesthetists (14.6%), 30 pre-operative nurses (14.6%), 51 surgeons (24.8%), 34 cancer specialist nurses (16.5%), 21 medical/clinical oncologists (10.2%), 25 physiotherapists/occupational therapists (12.1%) and 15 dieticians (7.3%)) completed the survey. The respondents worked at 19 hospital trusts across the UK and Ireland. Frailty scoring was not routinely performed in 63% of care settings, yet the majority of practitioners reported modifying their practice when providing and deciding on care for patients with frailty. Only 16% of organizations surveyed had a dedicated pathway for assessment and management of patients with frailty. A total of 37% of respondents reported access to prehabilitation services, 79% to enhanced recovery, and 27% to community rehabilitation teams. CONCLUSION: Practitioners from all groups surveyed considered that appropriate training, dedicated pathways for optimization, frailty specific performance indicators and evidence that frailty scoring had an impact on clinical outcomes and patient experience could all help to improve care for frail patients.

Inactivation of the group A Streptococcus regulator srv results in chromosome wide reduction of transcript levels, and changes in extracellular levels of Sic and SpeB.

Group A Streptococcus is characterized by the ability to cause a diverse number of human infections including pharyngitis, necrotizing fasciitis, toxic shock syndrome, and acute rheumatic fever, yet the regulation of streptococcal genes involved in disease processes and survival in the host is not completely understood. Genome scale analysis has revealed a complex regulatory network including 13 two-component regulatory systems and more than 100 additional putative regulators, the majority of which remain uncharacterized. Among these is the streptococcal regulator of virulence, Srv, the first Group A Streptococcus member of the Crp/Fnr family of transcriptional regulators. Previous work demonstrated that the loss of srv resulted in a significant decrease in Group A Streptococcus virulence. To begin to define the gene products influenced by Srv, we combined microarray and two-dimensional gel electrophoresis analysis. Loss of srv results in a chromosome wide reduction of gene transcription and changes in the production of the extracellular virulence factors Sic (streptococcal inhibitor of complement) and SpeB (cysteine proteinase). Sic levels are reduced in the srv mutant, whereas the extracellular concentration and activity of SpeB is increased. These data link Srv to the increasingly complex GAS regulatory network.

Effectiveness of Quality Improvement Interventions at Reducing Inappropriate Cardiac Imaging: A Systematic Review and Meta-Analysis.

BACKGROUND: Between 5% and 25% of cardiac imaging tests are performed for inappropriate indications. Studies have examined the impact of appropriate use criteria-based quality improvement initiatives on inappropriate testing, but they have not been systematically evaluated. METHODS AND RESULTS: We performed a systematic review of studies evaluating quality improvement initiatives aimed at reducing inappropriate cardiac imaging. The primary outcome was the proportion of inappropriate tests based on appropriate use criteria. Studies were analyzed using a random effects meta-analysis model, and heterogeneity was examined using subgroup analyses. We identified 6 observational studies and 1 randomized control trial. Most interventions (n=6) had a formal education component, and 5 included a mechanism for physician audit and feedback. Although these interventions were associated with lower odds of inappropriate testing (odds ratio, 0.44 [95% confidence interval, 0.32-0.61]; P<0.001), significant heterogeneity was observed (I(2)=70%), which was best explained by the utilization of physician audit and feedback. Interventions that employed physician audit and feedback were associated with significantly lower odds of inappropriate testing (odds ratio, 0.36 [95% confidence interval, 0.31-0.41]; P<0.001; I(2)=0%), whereas those that did not had no effect (odds ratio, 0.89 [95% confidence interval, 0.61-1.29]; P=0.51; I(2)=0%; P value for difference <0.001). All studies had potential sources of bias that could have affected the observed estimates. CONCLUSIONS: Interventions using physician audit and feedback are associated with lower odds of inappropriate cardiac testing. Further research is needed to evaluate a greater diversity of intervention types, with improved study designs.

Medical students' experiences working with frequently rotating pediatric inpatient attending physicians.

OBJECTIVE: To explore medical students' experiences working with frequently rotating pediatric inpatient attending physicians. METHODS: We performed a qualitative study using focus groups and individual interviews of medical students who rotated on the general pediatric inpatient service at Children's Hospital Colorado. The majority of inpatient pediatric attending physicians worked 1-week blocks. We used a semistructured interview guide and analyzed data using the constant comparative method. In accordance with the grounded theory method, codes were developed using an iterative approach, and major themes were identified. Analysis indicated theoretical saturation was achieved. We created a theory that arose from analysis of the data. RESULTS: Twenty-seven medical students participated. Data analysis yielded 6 themes: learning climate, continuity, student resilience, opportunity to progress, growth into a physician, and evaluation. In the learning climate, the emotional environment was often stressful, although students valued exposure to different patient care and teaching styles. Senior resident continuity promoted student function; lack of continuity with attending physicians inhibited relationship development. Students were resilient in adjusting to changing faculty with different expectations. In the context of frequently rotating faculty, students had difficulty showing improvement to a single attending physician after feedback, which limited students' opportunities to progress. Students perceived summative evaluation as less meaningful in the absence of having a relationship with their attending physicians. CONCLUSIONS: Medical students valued exposure to different patient care and teaching styles. However, frequently changing attending physicians caused students stress and limited students' perceived ability to achieve and show professional growth.

Ruptured aneurysm of an aberrant left hepatic artery.

Although rare, the high mortality associated with visceral artery aneurysms highlights the importance of their prompt diagnosis and treatment. This report details the acute presentation, diagnosis and management of a 51-year-old man with a non-traumatic ruptured aneurysm of an aberrant left hepatic artery. This is just the second case of a rupture of this aberrant artery reported in the literature, and the only one to be treated using endovascular techniques. An up-to-date review of the investigation and surgical/endovascular management of visceral aneurysms in relation to this case is included.

Fluctuations in species-level protein expression occur during element and nutrient cycling in the subsurface.

While microbial activities in environmental systems play a key role in the utilization and cycling of essential elements and compounds, microbial activity and growth frequently fluctuates in response to environmental stimuli and perturbations. To investigate these fluctuations within a saturated aquifer system, we monitored a carbon-stimulated in situ Geobacter population while iron reduction was occurring, using 16S rRNA abundances and high-resolution tandem mass spectrometry proteome measurements. Following carbon amendment, 16S rRNA analysis of temporally separated samples revealed the rapid enrichment of Geobacter-like environmental strains with strong similarity to G. bemidjiensis. Tandem mass spectrometry proteomics measurements suggest high carbon flux through Geobacter respiratory pathways, and the synthesis of anapleurotic four carbon compounds from acetyl-CoA via pyruvate ferredoxin oxidoreductase activity. Across a 40-day period where Fe(III) reduction was occurring, fluctuations in protein expression reflected changes in anabolic versus catabolic reactions, with increased levels of biosynthesis occurring soon after acetate arrival in the aquifer. In addition, localized shifts in nutrient limitation were inferred based on expression of nitrogenase enzymes and phosphate uptake proteins. These temporal data offer the first example of differing microbial protein expression associated with changing geochemical conditions in a subsurface environment.

Characterization and transcription of arsenic respiration and resistance genes during in situ uranium bioremediation.

The possibility of arsenic release and the potential role of Geobacter in arsenic biogeochemistry during in situ uranium bioremediation was investigated because increased availability of organic matter has been associated with substantial releases of arsenic in other subsurface environments. In a field experiment conducted at the Rifle, CO study site, groundwater arsenic concentrations increased when acetate was added. The number of transcripts from arrA, which codes for the α-subunit of dissimilatory As(V) reductase, and acr3, which codes for the arsenic pump protein Acr3, were determined with quantitative reverse transcription-PCR. Most of the arrA (>60%) and acr3-1 (>90%) sequences that were recovered were most similar to Geobacter species, while the majority of acr3-2 (>50%) sequences were most closely related to Rhodoferax ferrireducens. Analysis of transcript abundance demonstrated that transcription of acr3-1 by the subsurface Geobacter community was correlated with arsenic concentrations in the groundwater. In contrast, Geobacter arrA transcript numbers lagged behind the major arsenic release and remained high even after arsenic concentrations declined. This suggested that factors other than As(V) availability regulated the transcription of arrA in situ, even though the presence of As(V) increased the transcription of arrA in cultures of Geobacter lovleyi, which was capable of As(V) reduction. These results demonstrate that subsurface Geobacter species can tightly regulate their physiological response to changes in groundwater arsenic concentrations. The transcriptomic approach developed here should be useful for the study of a diversity of other environments in which Geobacter species are considered to have an important influence on arsenic biogeochemistry.

Utility of 64 detector coronary computed tomographic angiography in patients with and without prior equivocal stress tests.

This study sought to compare and the utility of cardiac computed tomographic angiography (CCTA) in patients with and without prior equivocal stress testing, and the subsequent need for invasive angiography and revascularization after CCTA. Evidence for the clinical utility of CCTA in the assessment of low to intermediate risk patients with equivocal stress testing is limited. Consecutive patients referred for outpatient CCTA for evaluation of suspected CAD with and without prior equivocal stress testing were included. CCTA studies were performed on a 64 detector scanner (Toshiba Aquilion). The diagnostic yield of CCTA for coronary stenoses and the subsequent need of the patients for invasive angiography and revascularization was evaluated. Of 228 patients evaluated, 43.9% were male, average age 59.3 ± 10.3. 66.2% (n = 151) had an equivocal stress test prior to CCTA. The prevelance of significant lesions (>50% stenosis) was high at 31% (n = 71), and was similar for those with and without a prior equivocal stress test (29.1 vs. 35.0%, P = NS). During a mean follow up of 1.4 ± 0.4 years, all patients with normal or stenosis by CCTA of <50% remained free from revascularization. Among those with a >50% stenosis by CCTA, the revascularization rate was 33.8%. The rates of angiography and revascularization were similar in those with or without prior stress tests (19 vs. 27%, P = 0.13 and 12 vs. 7.8%, P = 0.34 respectively). Regardless of whether or not patients had prior equivocal stress tests, CCTA detected a substantial number of obstructive CAD lesions and effectively identified the need for subsequent invasive angiography and revascularization. It appears to be a very promising triage test in this population.

Acute coronary syndrome in pregnancy.

Acute coronary syndrome (ACS) in pregnancy has traditionally been considered to be a rare event, but the combination of normal physiological changes of pregnancy and more prevalent cardiovascular risk factors are increasing its incidence in this population. The present report describes a 39 year-old woman that is seven weeks pregnant presenting with a non ST elevation myocardial infarction. The incidence, risk factors, pathophysiology and management of ACS in pregnancy are discussed.

Unraveling Brucella genomics and pathogenesis in immunocompromised IRF-1-/- mice.

PROBLEM: Brucellosis causes abortion in domestic animals and Malta fever in humans. Comparison of Brucella species genomes may reveal potential virulence mechanisms. Engineering bioluminescent Brucella would permit monitoring bacterial dissemination. METHOD OF STUDY: Microarray of the B. melitensis genome allowed comparison of gene content from six Brucella species. Bioluminescent B. melitensis strains were developed using transposon mutagenesis permitting the study of pathogenic Brucella in mice. Monitoring bacterial dissemination as well as organ localization permits evaluating the role of genes and genomic islands in mutant bacteria. RESULTS: Comparative genomic analysis revealed 217 ORFs altered in five Brucella species and were often found in islands. Bioluminescent bacteria disseminated from the injection site to liver, spleen, inguinal lymph nodes, testes and submanibular region. CONCLUSIONS: Genomic islands contribute to Brucella pathogenicity. Biophotonic imaging suggests that Brucella dissemination in mice parallels acute and chronic infections of humans.

Identification of srv, a PrfA-like regulator of group A streptococcus that influences virulence.

We have identified a Crp/Fnr-like transcriptional regulator of Streptococcus pyogenes that when inactivated attenuates virulence. The gene, named srv for streptococcal regulator of virulence, encodes a 240-amino-acid protein with 53% amino acid similarity to PrfA, a transcriptional activator of virulence in Listeria monocytogenes.

Characterization of an extracellular virulence factor made by group A Streptococcus with homology to the Listeria monocytogenes internalin family of proteins.

Leucine-rich repeats (LRR) characterize a diverse array of proteins and function to provide a versatile framework for protein-protein interactions. Importantly, each of the bacterial LRR proteins that have been well described, including those of Listeria monocytogenes, Yersinia pestis, and Shigella flexneri, have been implicated in virulence. Here we describe an 87.4-kDa group A Streptococcus (GAS) protein (designated Slr, for streptococcal leucine-rich) containing 10 1/2 sequential units of a 22-amino-acid C-terminal LRR homologous to the LRR of the L. monocytogenes internalin family of proteins. In addition to the LRR domain, slr encodes a gram-positive signal secretion sequence characteristic of a lipoprotein and a putative N-terminal domain with a repeated histidine triad motif (HxxHxH). Real-time reverse transcriptase PCR assays indicated that slr is transcribed abundantly in vitro in the exponential phase of growth. Flow cytometry confirmed that Slr was attached to the GAS cell surface. Western immunoblot analysis of sera obtained from 80 patients with invasive infections, noninvasive soft tissue infections, pharyngitis, and rheumatic fever indicated that Slr is produced in vivo. An isogenic mutant strain lacking slr was significantly less virulent in an intraperitoneal mouse model of GAS infection and was significantly more susceptible to phagocytosis by human polymorphonuclear leukocytes. These studies characterize the first GAS LRR protein as an extracellular virulence factor that contributes to pathogenesis and may participate in evasion of the innate host defense.