Gut Microbiota Modulation of Efficacy and Toxicity of Cancer Chemotherapy and Immunotherapy.

Accumulating evidence supports not only the functional role of the gut microbiome in cancer development and progression but also its role in defining the efficacy and toxicity of chemotherapeutic agents (5-fluorouracil, cyclophosphamide, irinotecan, oxaliplatin, gemcitabine, methotrexate) and immunotherapeutic compounds (anti-programmed death-ligand 1/anti-programmed cell death protein 1 and anti-cytotoxic T-lymphocyte-associated antigen 4). This evidence is supported in numerous in vitro, animal, and clinical studies that highlight the importance of microbial mechanisms in defining therapeutic responses. The microbiome therefore shapes oncologic outcomes and is now being leveraged for the development of novel personalized therapeutic approaches in cancer treatment. However, if the microbiome is to be successfully translated into next-generation oncologic treatments, a new multimodal model of the oncomicrobiome must be conceptualized that incorporates gut microbial cometabolism of pharmacologic agents into cancer care. The objective of this review is therefore to outline the current knowledge of oncologic pharmacomicrobiomics and to describe how the multiparametric functions of the gut microbiome influence treatment response across cancer types. The secondary objective is to propose innovative approaches for modulating the gut microbiome in clinical environments that improve therapy efficacy and diminish toxic effects derived from antineoplastic agents for patient benefit.

'Something that helped the whole picture': Experiences of parents offered rapid prenatal exome sequencing in routine clinical care in the English National Health Service.

OBJECTIVES: In October 2020, rapid prenatal exome sequencing (pES) was introduced into routine National Health Service (NHS) care in England. This study aimed to explore parent experiences and their information and support needs from the perspective of parents offered pES and of health professionals involved in its delivery. METHODS: In this qualitative study, semi-structured interviews were conducted with 42 women and 6 male partners and 63 fetal medicine and genetic health professionals. Interviews were transcribed verbatim and analysed using thematic analysis. RESULTS: Overall views about pES were positive and parents were grateful to be offered the test. Highlighted benefits of pES included the value of the additional information for pregnancy management and planning for future pregnancies. An anxious wait for results was common, often associated with the need to make decisions near to 24 weeks in pregnancy when there are legal restrictions for late termination. Descriptions of dealing with uncertainty were also common, even when results had been returned. Many parents described pES results as informing decision-making around whether or not to terminate pregnancy. Some professionals were concerned that a non-informative result could be overly reassuring and highlighted that careful counselling was needed to ensure parents have a good understanding of what the result means for their pregnancy. Emotional support from professionals was valued; however, some parents felt that post-test support was lacking. CONCLUSION: Parents and professionals welcomed the introduction of pES. Results inform parents' decision-making around the termination of pregnancy. When there are no diagnostic findings or uncertain findings from pES, personalised counselling that considers scans and other tests are crucial. Directing parents to reliable online sources of information and providing emotional support throughout could improve their experiences of care.

Gut microbiota fermentation profiles of pre-digested mycoprotein (Quorn) using faecal batch cultures in vitro: a preliminary study.

High-fibre diets are beneficial for many health outcomes via a wide range of mechanisms including gut microbiota fermentation-derived short-chain fatty acid (SCFAs) production. Mycoprotein (marketed as Quorn) is a food high in fibre (>6 g/100 g wet weight (ww)) and protein (13 g/100 g ww) which has been shown to have positive effects on glycemic control and appetite in humans. Nevertheless, the mechanisms underpinning this are poorly understood. Here, we investigate the changes in gut microbiota α- and ß-diversity, pH and SCFAs production in faecal batch cultures supplemented with pre-digested mycoprotein (Quorn), soy, chicken and control (unsupplemented) using eight fresh stools from healthy donors. The results showed that pre-digested mycoprotein did not alter pH (p = .896), α- or ß-diversity of the gut microbiota when compared to the control, soy, and chicken. Nevertheless, chicken led to a significant increase in total SCFAs post-24 h vs. control (+57.07 mmol/L, p = .01). In particular, propionate increased when compared to soy (+19.59 mmol/L, p = .03) and the control (+23.19 mmol/L, p < .01). No other differences in SCFAs were detected. In conclusion, pre-digested mycoprotein was not fermented in vitro by healthy gut microbiota in the settings of this experiment.

Epigenetic factor siRNA screen during primary KSHV infection identifies novel host restriction factors for the lytic cycle of KSHV.

Establishment of viral latency is not only essential for lifelong Kaposi's sarcoma-associated herpesvirus (KSHV) infection, but it is also a prerequisite of viral tumorigenesis. The latent viral DNA has a complex chromatin structure, which is established in a stepwise manner regulated by host epigenetic factors during de novo infection. However, despite the importance of viral latency in KSHV pathogenesis, we still have limited information about the repertoire of epigenetic factors that are critical for the establishment and maintenance of KSHV latency. Therefore, the goal of this study was to identify host epigenetic factors that suppress lytic KSHV genes during primary viral infection, which would indicate their role in latency establishment. We performed an siRNA screen targeting 392 host epigenetic factors during primary infection and analyzed which ones affect the expression of the viral replication and transcription activator (RTA) and/or the latency-associated nuclear antigen (LANA), which are viral genes essential for lytic replication and latency, respectively. As a result, we identified the Nucleosome Remodeling and Deacetylase (NuRD) complex, Tip60 and Tip60-associated co-repressors, and the histone demethylase KDM2B as repressors of KSHV lytic genes during both de novo infection and the maintenance of viral latency. Furthermore, we showed that KDM2B rapidly binds to the incoming viral DNA as early as 8 hpi, and can limit the enrichment of activating histone marks on the RTA promoter favoring the downregulation of RTA expression even prior to the polycomb proteins-regulated heterochromatin establishment on the viral genome. Strikingly, KDM2B can also suppress viral gene expression and replication during lytic infection of primary gingival epithelial cells, revealing that KDM2B can act as a host restriction factor of the lytic cycle of KSHV during both latent and lytic infections in multiple different cell types.

Association of emergency department boarding times on hospital length of stay for patients with psychiatric illness.

BACKGROUND: Extended periods awaiting an inpatient bed in the emergency department (ED) may exacerbate the state of patients with acute psychiatric illness, increasing the time it takes to stabilise their acute problem in hospital. Therefore, we assessed the association between boarding time and hospital length of stay for psychiatric patients. METHODS: ED clinical records were linked to inpatient administrative records for all patients with a primary psychiatric diagnosis admitted to a Calgary, Alberta hospital between April 2014 and March 2018. The primary exposure was boarding time (admission decision to inpatient bed transfer), and primary outcome was inpatient length of stay. Confounders for this relationship, including indicators of illness severity, were selected a priori then the association was assessed using hierarchical Bayesian Poisson regression, which accounts for repeat observations of the same patient and differences between hospital sites. Changes in length of stay were measured using a rate ratio (ie, expected change in length of stay for each 1 hour increase in boarding time). RESULTS: A total of 19 212 admissions (14 261 unique patients) were included in the analysis. The average boarding time was 14 hours (range: 0-186 hours). Patients who were boarded for greater than 14 hours more frequently required a high-observation bed (14% vs 3.5%), received an antipsychotic (44% vs 14%) or received sedation (55% vs 33%) while in the ED. The probability that boarding time increased hospital length of stay (rate ratio: >1) was 92%, with a median increase for a patient boarded for 24 hours of 0.01 days. CONCLUSION: Boarding in the ED was associated with a high probability of increasing the hospital length of stay for psychiatric patients; however, the absolute increase is minimal. Although slight, this signal for longer length of stay may be a sign of increased morbidity for psychiatric patients held in the ED.

The Intestinal Barrier and Its Dysfunction in Patients with Metabolic Diseases and Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) represents an increasing cause of liver disease worldwide, mirroring the epidemics of obesity and metabolic syndrome. As there are still no licensed medications for treating the disease, there is an ongoing effort to elucidate the pathophysiology and to discover new treatment pathways. An increasing body of evidence has demonstrated a crosstalk between the gut and the liver, which plays a crucial role in the development and progression of liver disease. Among other intestinal factors, gut permeability represents an interesting factor at the interface of the gut-liver axis. In this narrative review, we summarise the evidence from human studies showing the association between increased gut permeability and NAFLD, as well as with type-2 diabetes and obesity. We also discuss the manipulation of the gut permeability as a potential therapeutical target in patients with NAFLD.

Using a Retrospective Secondary Data Analysis to Identify Risk Factors for Pulmonary Complications in Trauma Patients in Pietermaritzburg, South Africa.

BACKGROUND: The trauma burden in South Africa is significant. The objective of this project was to investigate the incidence of posttrauma pulmonary complications (PPCs) and to identify patient, health risks, and hospital factors, which predispose trauma patients to develop PPCs hospital in Pietermaritzburg, South Africa. METHODS: The design was a retrospective secondary data analysis of patients who presented as a trauma admission via the health systems' Hybrid Electronic Medical Registry. The final data set included 6382 trauma admissions. RESULTS: The PPC rate was 9.4% for patients with a surgical intervention versus 1.9% for those without a surgical intervention. Of the total 289 PPCs reported, the most common included pneumonia or atelectasis (46.4%) and prolonged ventilation (36.0%). The risk of developing a PPC was statistically significantly (P < 0.0001) associated with surgical intervention and the number of surgeries. CONCLUSIONS: The trauma burden in South Africa requires complex medical and surgical interventions. The incidence of PPCs is significantly associated with surgical intervention. With the increasing demand to harness data and improve patient care, the Hybrid Electronic Medical Registry proves to be a driver for quality improvement.

Systematic Review of Evidence-Based Guidelines for Prehospital Care.

Introduction: Multiple national organizations have identified a need to incorporate more evidence-based medicine in emergency medical services (EMS) through the creation of evidence-based guidelines (EBGs). Tools like the Appraisal of Guidelines for Research and Evaluation (AGREE) II and criteria outlined by the National Academy of Medicine (NAM) have established concrete recommendations for the development of high-quality guidelines. While many guidelines have been created that address topics within EMS medicine, neither the quantity nor quality of prehospital EBGs have been previously reported. Objectives: To perform a systematic review to identify existing EBGs related to prehospital care and evaluate the quality of these guidelines using the AGREE II tool and criteria for clinical guidelines described by the NAM. Methods: We performed a systematic search of the literature in MEDLINE, EMBASE, PubMED, Trip, and guidelines.gov, through September 2018. Guideline topics were categorized based on the 2019 Core Content of EMS Medicine. Two independent reviewers screened titles for relevance and then abstracts for essential guideline features. Included guidelines were appraised with the AGREE II tool across 6 domains by 3 independent reviewers and scores averaged. Two additional reviewers determined if each guideline reported the key elements of clinical practice guidelines recommended by the NAM via consensus. Results: We identified 71 guidelines, of which 89% addressed clinical aspects of EMS medicine. Only 9 guidelines scored >75% across AGREE II domains and most (63%) scored between 50 and 75%. Domain 4 (Clarity of Presentation) had the highest (79.7%) and domain 5 (Applicability) had the lowest average score across EMS guidelines. Only 38% of EMS guidelines included a reporting of all criteria identified by the NAM for clinical practice guidelines, with elements of a systematic review of the literature most commonly missing. Conclusions: EBGs exist addressing a variety of topics in EMS medicine. This systematic review and appraisal of EMS guidelines identified a wide range in the quality of these guidelines and variable reporting of key elements of clinical guidelines. Future guideline developers should consider established methodological and reporting recommendations to improve the quality of EMS guidelines.

The use of polyvinyl alcohol hydrogel implants in the lesser metatarsal heads. Is it safely doable? A cadaveric study.

BACKGROUND: The use of synthetic polyvinyl alcohol hydrogel (PVAH) implants for treatment of lesser toe metatarsophalangeal joint (MTPJ) arthritis is promising and currently limited by the size of implants available. The primary objective of this cadaveric study was to investigate the maximum drilling size and largest PVAH implant dimension that could be safely introduced while still preserving an intact bone rim of the lesser metatarsal heads. METHODS: Height and width of all lesser metatarsals were measured on CT and during anatomic dissection. Sequential reaming of the second to fourth metatarsals was performed. Maximum reaming size, largest implant inserted, and failure of the metatarsal head were recorded. Metatarsal head sizes were compared and a multiple regression analysis evaluated measurements that influenced maximum drilling and implant size. RESULTS: CT and anatomical measurements demonstrated significant correlation (ICC range, 0.-0.85). Mean values for height and width of the metatarsal heads were respectively: second (14.9 mm and 9.9 mm), third (14.8 mm and 8.8 mm), fourth (14.0 mm and 8.7 mm) and fifth (12.3 mm and 9.3 mm). All the second, third and fourth metatarsal heads could be safely drilled up to 7.5 mm, preserving an intact bone rim. At 80% of the time, the heads could be safely drilled up to 8.0 mm. Height of the metatarsal heads was the only factor to significantly influence the size of maximum reaming and implant introduced. In respectively 20%, 40% and 50% of the second, third, and fourth metatarsal heads, neither 8 mm nor 10 mm PVAH implants could be used. CONCLUSIONS: Our cadaveric study found that the even though the majority of the lesser metatarsal heads could be safely drilled up to 8 mm, the smallest PVAH implant size currently available in most countries (8 mm) could be inserted in most of the second, but only in about half of the third and fourth metatarsal heads. The remaining bone rim around inserted implants was considerably thin, usually measuring less than 1 mm. In order to optimize the use PVAH in lesser metatarsal heads, smaller implant options are needed.

Tapered arteriovenous grafts do not provide significant advantage over nontapered grafts in upper extremity dialysis access.

OBJECTIVE: Although tapered dialysis access grafts are often used in an effort to prevent ischemic steal, their efficacy is uncertain. Our goal was to use real-world data to assess the performance of these grafts with respect to primary patency and ischemic steal. METHODS: The Vascular Quality Initiative database was queried from 2010 to 2017 for all patients undergoing tapered dialysis grafts in the upper arm. Multivariable analysis was performed to analyze primary patency, ischemic steal, and reinterventions. RESULTS: We identified 3608 patients who received dialysis access grafts, 1473 tapered grafts and 2135 nontapered grafts. The mean age was 64.8 years, and 43.4% of the patients were male. Tapered grafts were used more often in female patients (60.5% vs 54%), nonwhite patients (53.3% vs 47.7%), patients with no previous access (28% vs 26.3%), grafts with an antecubital brachial artery origin (50% vs 44.4%), and grafts with an antecubital cephalic vein target (7.4% vs 3.7%; P < .05). Three-month outcomes between tapered and nontapered grafts were similar for wound infection (1.4% vs 2%; P = .31), ischemic steal (4.1% vs 4.6%; P = .58), and arm swelling (3.5% vs 2.9%; P = .38). Multivariable analyses revealed that in comparison to nontapered grafts, tapered grafts did not affect primary patency rates (hazard ratio [HR], 1.17; 95% confidence interval [CI], 0.96-1.42; P = .11), ischemic steal (HR, 1.03; 95% CI, 0.64-1.65; P = .92), difference in endovascular reintervention (HR, 1.08; 95% CI, 0.74-1.16; P = .5), or operative reintervention (HR, 1.25; 95% CI, 0.86-1.82; P = .24). CONCLUSIONS: Tapered grafts for upper extremity arteriovenous access do not affect primary patency, development of steal, or endovascular reintervention in comparison to nontapered grafts. Our findings do not support the routine use of these grafts in dialysis access to improve outcomes.

The success rate of first metatarsophalangeal joint lateral soft tissue release through a medial transarticular approach: A cadaveric study.

BACKGROUND: The objective of this study was to evaluate the success rate of first metatarsophalangeal joint (MTPJ) lateral soft tissue release through a medial transarticular approach. METHODS: Ten cadaveric specimens were used (6 females/4 males, mean age, 73.4years). Lateral release was performed through a 4cm medial approach using a number 15 blade. Surgical aim was to release four specific structures: lateral capsule, lateral collateral ligament (LCL), adductor hallucis tendon (AHT) and lateral metatarsosesamoid suspensory ligament (LMSL). Once completed, a dissection of the first intermetatarsal space was performed. Success rate was graded in accordance to the number of structures successfully released: 0% (no structures), 25% (1/4), 50% (2/4), 75% (3/4) and 100% (4/4). Inadvertent injuries to other soft tissue structures were recorded. RESULTS: The success rate for lateral soft tissue release was 100% in 7 cadaveric specimens, and respectively 75%, 50% and 25% in the other 3 specimens. The LCL was successfully released in all specimens. The lateral joint capsule, AHT and LMSL were released in 80% of the specimens. Chondral damage to the first metatarsal head, unintended release of the conjoined tendon and lateral head of the flexor hallucis brevis (FHB) occurred respectively in 40%, 50% and 20% of the specimens. CONCLUSIONS: Our cadaveric study demonstrated high success rate in the release of specific lateral soft tissue structures of the first MTPJ through a medial transarticular approach. Inadvertent release of the lateral head of the FHB, conjoined tendon and iatrogenic chondral damage of the first metatarsal head are complications to be considered. LEVEL OF EVIDENCE: Cadaveric study - Level V.

Hindfoot alignment of adult acquired flatfoot deformity: A comparison of clinical assessment and weightbearing cone beam CT examinations.

BACKGROUND: Clinical assessment of hindfoot alignment (HA) in adult acquired flatfoot deformity (AAFD) can be challenging and weightbearing (WB) cone beam CT (CBCT) may potentially better demonstrate this three-dimensional (3D) deformity. Therefore, we compared clinical and WB CBCT assessment of HA in patients with AAFD. METHODS: In this prospective study, we included 12 men and 8 women (mean age: 52.2, range: 20-88) with flexible AAFD. All subjects also underwent WB CBCT and clinical assessment of hindfoot alignment. Three fellowship-trained foot and ankle surgeons performed six hindfoot alignment measurements on the CT images. Intra- and Inter-observer reliabilities were calculated using intra-class correlation (ICC). Measurements were compared by paired T-tests, and p-values of less than 0.05 were considered significant. RESULTS: The mean of clinically measured hindfoot valgus was 15.2 (95% confidence interval [CI]: 11.5-18.8) degrees. It was significantly different from the mean values of all WB CBCT measurements: Clinical Hindfoot Alignment Angle, 9.9 (CI: 8.9-11.1) degrees; Achilles tendon/Calcaneal Tuberosity Angle, 3.2 (CI: 1.3-5.0) degrees; Tibial axis/Calcaneal Tuberosity Angle, 6.1 (CI: 4.3-7.8) degrees; Tibial axis/Subtalar Joint Angle 7.0 (CI: 5.3-8.8) degrees, and Hindfoot Alignment Angle 22.8 (CI: 20.4-25.3) degrees. We found overall substantial to almost perfect intra- (ICC range: 0.87-0.97) and inter-observer agreements (ICC range: 0.51-0.88) for all WB CBCT measurements. CONCLUSIONS: Using 3D WB CBCT can help characterize the valgus hindfoot alignment in patients with AAFD. We found the different CT measurements to be reliable and repeatable, and to significantly differ from the clinical evaluation of hindfoot valgus alignment. LEVEL OF EVIDENCE: Level II-prospective comparative study.

Nonoperative Treatment of Type IIA Supracondylar Humerus Fractures: Comparing 2 Modalities.

BACKGROUND: Although the recommended treatment for Gartland types I and III supracondylar humeral fractures is well-established, the optimal treatment for type II fractures without rotational malalignment remains controversial, involving circumferential casting or closed reduction and pinning. Our institution uses pronated flexion-taping for Gartland type IIA fractures. This theoretically removes external pressure secondary to circumferential casting, potentially decreasing risks of compartment syndrome and mitigating loss of reduction with extension while maintaining optimal flexion position for reduction. To our knowledge, these modalities have not yet been compared. METHODS: A retrospective chart review was performed to compare flexion-taping with cuff-and-collar immobilization versus traditional above-elbow casting at 90 to 100 degrees. It was hypothesized that closed reduction and flexion-taping of type IIA supracondylar fractures under sedation in the emergency department would result in comparable, if not superior, maintenance of reduction measured radiographically using Baumann angle and the lateral humeral capitellar angle (LHCA). Charts from 2010 to 2015 were reviewed for all patients between 2 and 8 years of age with type IIA fractures treated with cast or taping. RESULTS: A total of 39 patients were included with 16 in the cast group and 23 in the tape group. Mean age was 4.08±1.72 years across both groups. No significant change in either measure was seen at termination of immobilization (3 to 4 wk postreduction). Final lateral humeral capitellar angle in the taping group was 32.14±5.90 degrees compared with 28.23±7.27 degrees in the casting group (P=0.81). Final Baumann angle was 73.41±4.03 degrees in the taping group compared with 73.75±6.46 degrees (P=0.96). The only complication was a self-limiting rash experienced by 1 patient in the taping group. CONCLUSIONS: Both techniques were able to achieve and maintain adequate reduction in all cases with no significant difference in outcome measures. There were no major complications or conversions to surgical treatment. In this cohort, taping resulted in adequate reduction and safe immobilization for type IIA fractures comparable to cast immobilization. Further research will investigate clinical/radiographic outcomes on these patients to assess remodeling and function. LEVEL OF EVIDENCE: Level III-retrospective comparative study.

Open Re-rupture of the Achilles Tendon Following Minimally Invasive Repair: A Case Report.

In this report, we describe a rare complication of an open re-rupture of the Achilles tendon following a minimally invasive Achilles tendon repair on a healthy 29-year-old active male. The reinjury happened 19 weeks following the primary surgical repair of a spontaneous rupture, performed by minimally invasive technique with the help of a jig using partially absorbable sutures and four locking stitches. The wound of the open re-rupture was transverse, in a perpendicular orientation relative to the longitudinal approach used in the index procedure. Increased scar tissue formation, the absence of an adequate layer of paratenon overlying the primary tendon repair, and foreign-body reaction to the suture may have been involved in the occurrence of this unusual complication in the surgical treatment of Achilles tendon rupture.

Short- and long-term readmission rates after infrainguinal bypass in a safety net hospital are higher than expected.

OBJECTIVE: Readmission rates are expected to have an increasing effect on both the hospital bottom line and physician reimbursements. Safety net hospitals may be most vulnerable. We examined readmissions at 30 days, 90 days, and 1 year in a large safety net hospital to determine the magnitude and effect of short- and long-term readmission rates after lower extremity infrainguinal bypass in this setting. METHODS: All nonemergent extremity infrainguinal bypass performed at a large safety net hospital between 2008 and 2016 were identified. Patient demographic, social, clinical, and procedural details were extracted from the electronic medical record. An analysis of patients readmitted at 30 days, 90 days, and 1 year was completed to determine the details of the readmission. RESULTS: A total of 350 patients undergoing extremity infrainguinal bypass were identified. The most frequent indication was tissue loss (57%), followed by claudication (25.6%), and rest pain (17.4%). Patient insurance carriers included Medicare (61.7%), Medicaid (25.4%), and private (13%). The distal target was the popliteal and tibial artery in 52.6% and 47.4% cases, respectively. The majority of bypasses used autologous vein (73.1%). In-hospital complications included pulmonary complications (4.3%), urinary tract infection (3.1%), acute renal failure (2%), graft occlusion (2%), myocardial infarction (1.7%), bleeding (1.4%), surgical wound complications (1.1%), and stroke (0.9%). The 30-day readmission rate was 30% with the most common reasons for readmission being surgical wound complications, nonsurgical foot/leg wounds, nonextremity infectious causes, cardiac ischemia, and congestive heart failure. The 90-day readmission rate was 49.4% and the most common reasons for readmission from 31 to 90 days were nonsurgical foot/leg wounds, graft complications, surgical wound complications, cardiac ischemia, and contralateral leg morbidity. The readmission rate within 1 year was 72.2%. Readmission causes from 91 days to 1 year included graft complications, contralateral leg morbidity, nonextremity infectious, nonsurgical foot/leg wounds, cardiac ischemia, and congestive heart failure. A tibial bypass target was associated with 30-day (odds ratio [OR], 1.69; 95% confidence interval [CI], 1.06-2.69; P = .029) and 90-day (OR, 1.77; 95% CI, 1.14-2.74, P = .011) readmission. Nonprivate insurance (OR, 2.31; 95% CI, 1.17-4.57, P = .016), and critical limb ischemia (OR, 1.77; 95% CI, 1.14-2.74; P = .035) were associated with 1-year readmission. CONCLUSIONS: Short- and long-term readmission rates in a safety net setting are high. The 30-day rates in this study are higher than historically reported. This data sets baseline rates for 90-day and 1-year readmission for future analyses. Although the majority of short-term readmissions are related to the index procedure, long-term readmission rates are more frequently related to systemic comorbidities. Targeted patient interventions aimed at preventing the most common reasons for readmission may improve readmission rates, particularly among patients with nonprivate insurance. However, other risk factors, such as tibial target, may not be modifiable and a higher readmission rate may need to be accepted in this population.

Microbial signatures and continuum in endometrial cancer and benign patients.

BACKGROUND: Endometrial cancer is a multifactorial disease with inflammatory, metabolic and potentially microbial cues involved in disease pathogenesis. The endometrial cancer microbiome has been poorly characterised so far and studies have often overestimated bacterial biomass due to lack of integration of appropriate contamination controls. There is also a scarcity of evidence on the functionality of microbial microenvironments in endometrial cancer. This work addresses that knowledge gap by interrogating the genuine, contamination-free microbial signatures in the female genital tract and rectum of women with endometrial cancer and the mechanistic role of microbiome on carcinogenic processes. RESULTS: Here we sampled different regions of the reproductive tract (vagina, cervix, endometrium, fallopian tubes and ovaries) and rectum of 61 patients (37 endometrial cancer; 24 benign controls). We performed 16S rRNA gene sequencing of the V1-V2 hypervariable regions and qPCR of the 16S rRNA gene to qualitatively and quantitatively assess microbial communities and used 3D benign and endometrial cancer organoids to evaluate the effect of microbial products of L. crispatus, which was found depleted in endometrial cancer patients following primary analysis, on endometrial cell proliferation and inflammation. We found that the upper genital tract of a subset of women with and without endometrial cancer harbour microbiota quantitatively and compositionally distinguishable from background contaminants. Endometrial cancer was associated with reduced cervicovaginal and rectal bacterial load together with depletion of Lactobacillus species relative abundance, including L. crispatus, increased bacterial diversity and enrichment of Porphyromonas, Prevotella, Peptoniphilus and Anaerococcus in the lower genital tract and endometrium. Treatment of benign and malignant endometrial organoids with L. crispatus conditioned media exerted an anti-proliferative effect at high concentrations but had minimal impact on cytokine and chemokine profiles. CONCLUSIONS: Our findings provide evidence that the upper female reproductive tract of some women contains detectable levels of bacteria, the composition of which is associated with endometrial cancer. Whether this is a cause or consequence of cancer pathophysiology and what is the functional significance of this finding remain to be elucidated to guide future screening tools and microbiome-based therapeutics. Video Abstract.

Colonisation of hospital surfaces from low- and middle-income countries by extended spectrum ß-lactamase- and carbapenemase-producing bacteria.

Hospital surfaces can harbour bacterial pathogens, which may disseminate and cause nosocomial infections, contributing towards mortality in low- and middle-income countries (LMICs). During the BARNARDS study, hospital surfaces from neonatal wards were sampled to assess the degree of environmental surface and patient care equipment colonisation by Gram-negative bacteria (GNB) carrying antibiotic resistance genes (ARGs). Here, we perform PCR screening for extended-spectrum ß-lactamases (blaCTX-M-15) and carbapenemases (blaNDM, blaOXA-48-like and blaKPC), MALDI-TOF MS identification of GNB carrying ARGs, and further analysis by whole genome sequencing of bacterial isolates. We determine presence of consistently dominant clones and their relatedness to strains causing neonatal sepsis. Higher prevalence of carbapenemases is observed in Pakistan, Bangladesh, and Ethiopia, compared to other countries, and are mostly found in surfaces near the sink drain. Klebsiella pneumoniae, Enterobacter hormaechei, Acinetobacter baumannii, Serratia marcescens and Leclercia adecarboxylata are dominant; ST15 K. pneumoniae is identified from the same ward on multiple occasions suggesting clonal persistence within the same environment, and is found to be identical to isolates causing neonatal sepsis in Pakistan over similar time periods. Our data suggests persistence of dominant clones across multiple time points, highlighting the need for assessment of Infection Prevention and Control guidelines.

P10-A128†Trending of contamination rates across NHSBT eye banks.

INTRODUCTION: NHS Blood and Transplant Tissue and Eye Services (TES) is a human multi-tissue, tissue bank supplying tissue for transplant to surgeons throughout the UK. NHSBT has two Eye Banks.NHSBT investigated all our corneas discard due to contamination with the aim to review for any patterns. NHSBT Eye Banks performs initial Microbiology sampling on all Corneas in Corneas in Organ Culture Media at 7 Days. Corneas undergo a 2nd Microbiology sampling the day after the cornea is transferred into dextran median. MATERIALS AND METHODS: Any Microbiology positive media Identified pre-transplant are sent to NHSBT's Microbiology Reference Laboratory (MSL) for Identification. Any organisms which are identified post-dispatch are sent to a Referral Laboratory for rapid Identification and Sensitivity/Specificity Testing. FILTON EYE BANK: Contaminated Corneas in Organ Media: 2018- 28 (0.91%) 2019 -45 (1.10%), 2020- 27 (1.03%), 2021- 39 (1.41%), 2022- 43 (2.1%) (until 15/08/22)Most common Identified Organisms: C.Ablicans C. glabrata C.paraphilotisContaminated In Dextran Pre-Transplant: 2018- 4 (0.17%) 2019 -6 (0.18%), 2020- 9 (0.46%), 2021- 0 (0%), 2022- 3 (0.3%) (until 15/08/22). Most common Identified Organisms: Bacillus speciesContaminated in Dextran Post Transplant: 2018- 0 (0%) 2019 -8 (0.23%), 2020- 2(0.10%), 2021- 2 (0.08%), 2022- 1 (0.11%) (until 15/08/22). Most common Identified Organisms: Bacillus speciesDavid Lucas Eye Bank: Contaminated Corneas in Organ Media: 2020- 20(1.8%), 2021- 37(1.96%), 2022- 21(1.4%) (until 15/08/22). Most common Identified Organisms: C.Ablicans C. glabrata C.KefyrContaminated In Dextran Pre-Transplant: 2020- 6(0.8%), 2021- 2(0.14%), 2022- 1(0.08%) (until 15/08/22). Most common Identified Organisms: Bacillus speciesContaminated in Dextran Post Transplant: 2020- 2 (0.26%), 2021- 1 (0.07%), 2022- 2 (0.16%) (until 15/08/22). Most common Identified Organisms: Bacillus species DISCUSSION: Processes and facilities are of same standard between the two NHSBT Eye Banks and contamination rates are comparable. contamination is only identified in Approx1% of corneas processed. Corneas where growth is identified in Dextran is less than 1% of corneas Issued. Of the positive Microbiology samples identified post-Transplant, were mostly identified as Environmental Bacteria and had no patient impact on patient and assumed to have been contaminated by the operator.

Utility of head computed tomography for older adults with suspected delirium in the emergency department: A retrospective observational study.

BACKGROUND: Delirium in older people is associated with significant morbidity and mortality and has life-threatening etiologies making prompt recognition essential. Computed tomography of the head (CT-head) may have a role in determining the cause of delirium; however, inpatient studies suggest it is overused. There is a paucity of emergency department (ED)-based research surrounding the use of CT-head in delirium. This study aims to describe the utility of CT-head in older patients presenting to the ED with symptoms of delirium. METHODS: We conducted a retrospective chart review of patients 65 years and older with symptoms of delirium who visited local EDs over a 3.5-year period (2016-2020). We compared patients who did and did not receive CT-head. Our primary objective was to determine the proportion of acute findings in patients who received CT-head. Our secondary objectives were to describe the proportions of patients who did and did not receive CT-head in terms of their demographics, presenting symptoms, disposition, and indications for and results of CT-head scans. Chi-square tests were utilized for comparisons. RESULTS: A total of 630 encounters were identified through database searching; 526 met inclusion criteria. Thirty-four were excluded for presenting directly to consultants, leaving 492 included encounters. Of those who received a CT-head (n = 279), 13 (4.7%) had acute findings. Of the encounters with acute findings, four (30.77%) had focal neurological deficits (FND), and two (15.38%) had Glasgow Coma Scale (GCS) score < 14. Patients without CT-head (n = 213) were more likely to be discharged (p < 0.01) and less likely to have a FND (p < 0.01). CONCLUSIONS: CT-head is ordered for over half of older ED patients with symptoms of delirium despite infrequent acute findings. Acute findings typically occur in the context of symptoms suggestive of intracranial abnormalities such as FND or GCS < 14. This suggests physicians should be more selective when ordering CT-heads in patients with symptoms of delirium.

Identification of a Sub-Clinical Salmonella spp. Infection in a Dairy Cow Using a Commercially Available Stool Storage Kit.

Stool sampling is a useful tool for diagnosing gastrointestinal disease in veterinary medicine. The sub-clinical disease burden of Salmonella spp. in cattle can become significant for farmers. However, current methods of faecal sampling in a rural setting for diagnosis are not consistently sufficient for the preservation of Salmonella spp. in faeces. This study evaluated the use of a commercial stool storage kit for bacterial preservation in cow faecal samples compared to unpreserved stools placed into refrigeration at different time-points. A stool sample was collected per-rectum from one apparently healthy Holstein-Freisen cow. The sample was weighed and aliquoted into two sterile Falcon tubes and into two commercial kit tubes. The aliquots were then placed into refrigeration at 4 °C at 0, 24, and 96 h after processing. One commercial kit tube was not aliquoted and remained at ambient temperature. After 2 weeks, DNA was extracted from the samples and analysed using endpoint PCR, revealing a sub-clinical infection with Salmonella spp. The bacterium was best preserved when the stool was stored in the commercial kit at ambient temperature and re-homogenised immediately prior to DNA extraction. The unpreserved stool did not maintain obvious levels of Salmonella spp. after 24 h at ambient temperature. This commercial kit should be considered for use in the diagnosis of salmonellosis in cattle.