Diabetes mellitus does not alter mortality or hospitalisation risk in patients with newly diagnosed heart failure with preserved ejection fraction: Time to rethink pathophysiological models of disease progression.

INTRODUCTION: Type 2 diabetes is a common and adverse prognostic co-morbidity for patients with heart failure with reduced ejection fraction (HFrEF). The effect of diabetes on long-term outcomes for heart failure with preserved ejection fraction (HFpEF) is less established. METHODS: Prospective cohort study of patients referred to a regional HF clinic with newly diagnosed with HFrEF and HFpEF according to the 2016 European Society of Cardiology guidelines. The association between diabetes, all-cause mortality and hospitalisation was quantified using Kaplan-Meier or Cox regression analysis. RESULTS: Between 1st May 2012 and 1st May 2013, of 960 unselected consecutive patients referred with suspected HF, 464 and 314 patients met the criteria for HFpEF and HFrEF respectively. Within HFpEF and HFrEF groups, patients with diabetes were more frequently male and in both groups patients with diabetes were more likely to be treated with ß-adrenoceptor antagonists and angiotensin converting enzyme inhibitors. After adjustment for age, sex, medical therapy and co-morbidities, diabetes was associated with increased mortality in individuals with HFrEF (HR 1.46 95% CI: 1.05-2.02; p = .023), but not in those with HFpEF (HR 1.26 95% CI 0.92-1.72; p = .146). CONCLUSION: In unselected patients with newly diagnosed HF, diabetes is not an adverse prognostic marker in patients with HFpEF, but is in HFrEF.

Mediastinal Nontuberculous Mycobacterial Infection in Children: A Multidisciplinary Approach.

BACKGROUND: Mediastinal infections due to nontuberculous mycobacteria remain an exceedingly rare entity. Most cases in the published literature do not include pediatric patients. Due to their clinical infrequency, poor response to antimicrobial therapy and often precarious anatomical location, the optimal management of these lesions can be challenging. METHODS: Retrospective medical record review of 4 pediatric cases of mediastinal nontuberculous mycobacteria infection was undertaken. Each child presented with nonspecific respiratory symptoms, including significant acute airway obstruction and required a range of investigations to confirm the diagnosis. Nonresponsiveness to conservative measures and antimycobacterial therapy ultimately resulted in surgical intervention to obtain clinical improvement. RESULTS: All 4 children had extensive evaluation and multidisciplinary involvement in otolaryngology, respiratory medicine, pediatric surgery, infectious diseases and cardiothoracic surgery. They all eventually had their disease debulked via thoracotomy in addition to prolonged antimycobacterial therapy, with successful clinical outcomes. CONCLUSIONS: Mediastinal nontuberculous mycobacteria infections in the pediatric population are rare and diagnostically challenging. A high clinical suspicion should be maintained, and multidisciplinary input sought. Targeted surgery with adjuvant medical therapy can reduce disease burden with minimal long-term morbidity.

Is Transcatheter Aortic Valve Implantation (TAVI) Activity in Australia Consistent With International Guidelines?

BACKGROUND: Transcatheter aortic valve implantation (TAVI) did not receive regulatory approval in Australia until 2013, several years after Europe (2007) and America (2011). Consequently, the uptake of TAVI in Australia initially lagged behind international best practices. This study was undertaken to provide an update on the status of TAVI activity in Australia. METHOD: A descriptive population-level epidemiological study was performed. Annual activity data for both surgical aortic valve replacement (SAVR) and TAVI were obtained from the Australian Institute of Health and Welfare (AIHW) for the period from 1 July 2012 to 30 June 2022. Dynamic contemporaneous population data were obtained from the Australian Bureau of Statistics (ABS). Trends in absolute activity, population-adjusted activity and age cohort-adjusted activity were examined. RESULTS: Despite the impact of the COVID-19 pandemic on the Australian healthcare system, TAVI activity has continued to increase. Annual TAVI activity now exceeds annual SAVR activity (3,967 vs 3,870), albeit driven by TAVI in patients aged 85+ years. Population-adjusted TAVI activity now exceeds the reported European average (15.3 vs 14.1 per 100,000 persons). The point of equipoise for the choice between SAVR and TAVI is the 75-79 age cohort (50% vs 50%). CONCLUSIONS: Australian TAVI activity is now consistent with international best practice.

Quantifying the Impact of Motions on Human Aiming Performance: Evidence from Eye Tracking and Bio-Signals.

Working on a moving platform can significantly impede human performance. Previous studies on moving vehicles have often focused on the overall impact on general task performance, whereas our study's emphasis is on precise hand movements, exploring the interaction between body motion and the escalation of task difficulty. We recruited 28 participants to engage in reciprocal aiming tasks, following Paul Fitts's setting, under both in-motion and stationary conditions. The task index of difficulty (ID) was manipulated by varying the width of the targets and the distance between the targets. We measured participants' movement time (MT), performance errors, and monitored their eye movements using an eye-tracking device, heart rate (HR), and respiration rate (RR) during the tasks. The measured parameters were compared across two experimental conditions and three ID levels. Compared to the stationary conditions, the in-motion conditions degraded human aiming performance, resulting in significantly prolonged MT, increased errors, and longer durations of eye fixations and saccades. Furthermore, HR and RR increased under the in-motion conditions. Linear relationships between MT and ID exhibited steeper slopes under the in-motion conditions compared to the stationary conditions. This study builds a foundation for us to explore the control mechanisms of individuals working in dynamic and demanding environments, such as pilots in airplanes and paramedics in ambulances.

Revision of Thraulus Eaton 1881 (Ephemeroptera: Leptophlebiidae: Choroterpinae).

The genus Thraulus is widespread throughout much of the Eastern Hemisphere. Since Eaton established Thraulus in 1881, 62 species have, at one time or another, been placed in this genus. Thirty-eight of those species were eventually moved to other genera. Any comprehensive study of the remaining species, based on the published literature, is difficult as they were described by many authors, using different criteria, over a period of 142 years. The purpose of this study was to redescribe this genus, based on previously described species and nine new species, and to provide a format for future taxonomic and morphological studies of Thraulus. Redescriptions of most species were based on direct examination of external morphological characters. Descriptions or diagnoses of species, whose types were unavailable for study, were made using the original published description and additional information provided by authors of several of those species. The following species were studied: Thraulus amravati Vasanth, Subramanian & Selvakumar, 2022; T. bellus Eaton, 1881; T. bishopi Peters & Tsui, 1972; T. cuspidatus Vasanth, Subramanian & Selvakumar, 2022; T. demoulini Peters & Tsui, 1973; T. fasciatus (Kimmins, 1956); T. fatuus Kang & Yang, 1994; T. femoratus Li, Liu & Zhou, 2006; T. gopalani Grant & Sivaramakrishnan, 1985; T. jacobusi Isack, Srinivasan, Sivaruban & Barathy, 2022; T. macilentus Kang & Yang, 1994; T. malabarensis Vasanth, Subramanian & Selvakumar, 2022; T. mudumalaiensis Soman, 1991; T. plumeus Selvakumar, Vasanth & Subramanian, 2022; T. semicastaneus (Gillies, 1951); T. thiagarajani Balasubramanian & Muthukatturaja, 2019; T. thraker Jacob, 1988; T. torrentis (Gillies, 1964); T. turbinatus (Ulmer, 1909); T. umbrosus Kang & Yang, 1994; and T. vellimalaiensis Vasanth, Subramanian & Selvakumar, 2022. Nine new species of Thraulus are described: T. connubialis sp. nov., Malaysia; T. cursus sp. nov., Japan; T. eatoni sp. nov., Indonesia; T. ishiwatai sp. nov., Japan; T. madagasikarensis sp. nov., Madagascar; T. nihonensis sp. nov., Japan; T. opifer sp. nov., Australia; T. parentalis sp. nov., Malaysia; and T. petersorum sp. nov., Malaysia. Thraulus can be distinguished from all other genera of Leptophlebiidae by the following combination of characters: In the imagos, 1) upper portion of eyes oval-suboval, major axes diverge anteriorly; 2) vein MA fork of fore wings symmetrical; 3) vein MP fork of fore wings asymmetricala cross vein connects base of MP2 to MP1, MP fork closer to base of wing than Rs fork; 4) strongly oblique cross vein extends between veins R4+5 and MA1 just apical to fork of vein MA; 5) 2 cubital intercalary veins in fore wings; 6) costal projection on hind wings well-developed, bluntly rounded to acutely pointed; 7) claws dissimilarone blunt and pad-like, the other apically hooked; 8) penes long, relatively straight, narrow, parallel, usually contiguous mesally but not fused, apex may have lateral projections; 9) sternum 7 of female with posterior margin straight or shallowly concave or convex mesally; and 10) sternum 9 of females rounded apically. In addition, penile spines occur on most species. In the nymphs, 1) lateral margins of clypeus parallel; 2) width of labrum subequal to width of clypeus; 3) 2 dorsal rows of setae on labrum; 4) venter of labrum with 1 row of short stout setae on either side of midline near anterior margin, rows curve mesally; 5) hypopharynx with small, rounded, posterolateral projections on arms of superlingua; 6) large spine on posterolateral corners of terga 69, 79 or 89; 7) gills 17 dissimilar: gill 1 composed of 1 or 2 subulate lamellae or a dorsal subulate lamella and a ventral fimbriate oval lamella, and gills 27 composed of dorsal and ventral oval lamellae with fimbriate margins. Two species continue to be nomen dubiumT. siewertii (Weyenbergh, 1883) and T. vogleri (Weyenbergh, 1883). Thraulus grandis Gose, 1980 is considered nomen nudum. A review of published phylogenetic studies involving Thraulus is provided. With the species discussed in this paper, along with reports of additional new species to be described, Thraulus has the potential to be included among the more specious genera of Ephemeroptera.

Assessment of a goal-directed perfusion strategy through an oxygen delivery audit.

INTRODUCTION: Evidence supports the role of oxygen delivery (DO2) in ameliorating acute kidney injury (AKI). While instrumentation for continuous DO2 measurement exists, a simplified method has been reported for targeting a specific DO2 index (DO2i), commonly referred to as a goal-directed perfusion (GDP) strategy, by using a reference table and available data such as body surface area and continuous haematocrit values. This simplified approach can also be used for quality auditing via archived data. METHODS: This retrospective sequential audit was conducted to assess the impact of employing a GDP strategy within our institution by examining perfusion practices, DO2 levels and renal outcomes before and after implementation. A total of 246 patients undergoing elective primary coronary revascularisation were included: 125 patients in the pre-change group and 121 patients in the post-change group. A DO2i threshold above 280 mL/min/m2 was targeted in the post-GDP group. RESULTS: While both groups maintained a mean DO2 above the threshold, the post-GDP group exhibited a higher average DO2i (311 vs 291 mL/min/m2). The GDP strategy led to higher nadir DO2i (255 vs 225, p < .001) and was coupled with a reduction in the time below the 280 mL/min/m2 threshold (30 min vs 50 min, p < .001). The average cardiac index in the post-GDP group was higher (1.87 vs 1.65, p < .001) while also demonstrating a smaller creatinine rise of 6.8% compared to 13.5% in the control group (p = .035). There was no difference in AKI or mortality rates between the groups. CONCLUSION: The implementation of the GDP strategy demonstrated an enhancement in oxygen delivery during cardiopulmonary bypass, primarily attributable to elevated pump flow rates. A statistically significant decrease in serum creatinine levels was observed. The published reference table emerged as a simple yet effective tool in optimising our GDP strategy.

Community-wide genome sequencing reveals 30 years of Darwin's finch evolution.

A fundamental goal in evolutionary biology is to understand the genetic architecture of adaptive traits. Using whole-genome data of 3955 of Darwin's finches on the Galápagos Island of Daphne Major, we identified six loci of large effect that explain 45% of the variation in the highly heritable beak size of Geospiza fortis, a key ecological trait. The major locus is a supergene comprising four genes. Abrupt changes in allele frequencies at the loci accompanied a strong change in beak size caused by natural selection during a drought. A gradual change in Geospiza scandens occurred across 30 years as a result of introgressive hybridization with G. fortis. This study shows how a few loci with large effect on a fitness-related trait contribute to the genetic potential for rapid adaptive radiation.

Association of Protein Intake with Recurrence and Survival Following Primary Treatment of Ovarian Cancer.

BACKGROUND: Malnutrition is common during treatment of ovarian cancer, and 1 in 3 patients report multiple symptoms affecting food intake after primary treatment. Little is known about diet posttreatment in relation to ovarian cancer survival; however, general recommendations for cancer survivors are to maintain a higher level of protein intake to support recovery and minimize nutritional deficits. OBJECTIVES: To investigate whether intake of protein and protein food sources following primary treatment of ovarian cancer is associated with recurrence and survival. METHODS: Intake levels of protein and protein food groups were calculated from dietary data collected ∼12 mo postdiagnosis using a validated FFQ in an Australian cohort of women with invasive epithelial ovarian cancer. Disease recurrence and survival status were abstracted from medical records (median 4.9 y follow-up). Cox proportional hazards regression was used to calculate adjusted HRs and 95% CIs for protein intake and progression-free and overall survival. RESULTS: Among 591 women who were progression-free at 12 mo follow-up, 329 (56%) subsequently experienced cancer recurrence and 231 (39%) died. A higher level of protein intake was associated with better progression-free survival (>1-1.5 compared with ≤1 g/kg body weight, HRadjusted: 0.69, 95% CI: 0.48, 1.00; >1.5 compared with ≤1 g/kg, HRadjusted: 0.61, 95% CI: 0.41, 0.90; >20% compared with ≤20% total EI from protein, HRadjusted: 0.77, 95% CI: 0.61, 0.96). There was no evidence for better progression-free survival with any particular protein food sources. There was a suggestion of better overall survival among those with higher total intakes of animal-based protein foods, particularly dairy products (HR: 0.71; 95% CI: 0.51, 0.99 for highest compared with lowest tertiles of total dairy intake). CONCLUSIONS: After primary treatment of ovarian cancer, a higher level of protein intake may benefit progression-free survival. Ovarian cancer survivors should avoid dietary practices that limit intake of protein-rich foods.

Phenotypic divergence of traits that mediate antagonistic and mutualistic interactions between island and continental populations of the tropical plant, Tribulus cistoides (Zygophyllaceae).

Island systems have long served as a model for evolutionary processes due to their unique species interactions. Many studies of the evolution of species interactions on islands have focused on endemic taxa. Fewer studies have focused on how antagonistic and mutualistic interactions shape the phenotypic divergence of widespread nonendemic species living on islands. We used the widespread plant Tribulus cistoides (Zygophyllaceae) to study phenotypic divergence in traits that mediate antagonistic interactions with vertebrate granivores (birds) and mutualistic interactions with pollinators, including how this is explained by bioclimatic variables. We used both herbarium specimens and field-collected samples to compare phenotypic divergence between continental and island populations. Fruits from island populations were larger than on continents, but the presence of lower spines on mericarps was less frequent on islands. The presence of spines was largely explained by environmental variation among islands. Petal length was on average 9% smaller on island than continental populations, an effect that was especially accentuated on the Galápagos Islands. Our results show that Tribulus cistoides exhibits phenotypic divergence between island and continental habitats for antagonistic traits (seed defense) and mutualistic traits (floral traits). Furthermore, the evolution of phenotypic traits that mediate antagonistic and mutualistic interactions partially depended on the abiotic characteristics of specific islands. This study shows the potential of using a combination of herbarium and field samples for comparative studies on a globally distributed species to study phenotypic divergence on island habitats.

Common analgesics and ovarian cancer survival: the Ovarian cancer Prognosis And Lifestyle (OPAL) Study.

BACKGROUND: Most women with ovarian cancer (OC) are diagnosed with advanced disease. They often experience recurrence after primary treatment, and their subsequent prognosis is poor. Our goal was to evaluate the association between use of nonsteroidal antiinflammatory drugs (NSAIDs), including regular and low-dose aspirin, and 5-year cancer-specific survival after an OC diagnosis. METHODS: The Ovarian cancer Prognosis And Lifestyle study is a prospective population-based cohort of 958 Australian women with OC. Information was gathered through self-completed questionnaires. We classified NSAID use during the year prediagnosis and postdiagnosis as none or occasional (<1 d/wk), infrequent (1-3 d/wk), and frequent (≥4 d/wk) use. We measured survival from the start of primary treatment: surgery or neoadjuvant chemotherapy for analyses of prediagnosis use, or 12 months after starting treatment (postdiagnosis use) until the earliest of date of death from OC (other deaths were censored) or last follow-up to 5 years. We used Cox proportional hazards regression to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) and applied inverse-probability of treatment weighting to minimize confounding. We also calculated restricted mean survival times. RESULTS: Compared with nonusers and infrequent users, we observed better survival associated with frequent NSAID use prediagnosis (HR = 0.73, 95% CI = 0.55 to 0.97) or postdiagnosis (HR = 0.65, 95% CI = 0.45 to 0.94). Estimates were similar for aspirin and nonaspirin NSAIDs, new and continuous users and in weighted models. These differences would translate to a 2.5-month increase in mean survival by 5 years postdiagnosis. There was no association with acetaminophen. CONCLUSIONS: Our findings confirm a previous study suggesting NSAID use might improve OC survival.

Evaluation of out-of-pocket pay genetic testing in a publicly funded healthcare system.

When genetic tests are not funded publicly, out-of-pocket (OOP) pay options may be discussed with patients. We evaluated trends in genetic testing and OOP pay for two publicly funded British Columbia clinical programs serving >12 000 patients/year (The Hereditary Cancer Program [HCP] and Provincial Medical Genetics Program [PMGP]) between 2015-2019. Linear and regression models were used to explore the association of OOP pay with patient demographic variables at HCP. An interrupted time series and linear and logistic regression models were used on PMGP data to examine the effect of a change in the funding body. The total number of tests completed through PMGP, and HCP increased by 260% and 320%, respectively. OOP pay increased at HCP by 730%. The mean annual income of patients who paid OOP at HCP was ≥$3500 higher than in the group with funded testing (p < 0.0001). The likelihood of OOP pay increased at PMGP before the funding body change (OR per month: 1.07; 95% CI: 1.04, 1.10); while this likelihood had an immediate 87% drop when the change occurred (OR: 0.13; 95% CI: 0.06, 0.32). Patients with higher incomes are more likely to pay OOP. Financial barriers can create disparities in clinical outcomes. Funding decisions have a significant impact on rate of OOP pay.

Spatiotemporal variations in retrovirus-host interactions among Darwin's finches.

Endogenous retroviruses (ERVs) are inherited remnants of retroviruses that colonized host germline over millions of years, providing a sampling of retroviral diversity across time. Here, we utilize the strength of Darwin's finches, a system synonymous with evolutionary studies, for investigating ERV history, revealing recent retrovirus-host interactions in natural populations. By mapping ERV variation across all species of Darwin's finches and comparing with outgroup species, we highlight geographical and historical patterns of retrovirus-host occurrence, utilizing the system for evaluating the extent and timing of retroviral activity in hosts undergoing adaptive radiation and colonization of new environments. We find shared ERVs among all samples indicating retrovirus-host associations pre-dating host speciation, as well as considerable ERV variation across populations of the entire Darwin's finches' radiation. Unexpected ERV variation in finch species on different islands suggests historical changes in gene flow and selection. Non-random distribution of ERVs along and between chromosomes, and across finch species, suggests association between ERV accumulation and the rapid speciation of Darwin's finches.

Impact of light therapy on rotating night shift workers: the EuRhythDia study.

AIMS: Disturbances in circadian rhythms may promote cardiometabolic disorders in rotating night shift workers (r-NSWs). We hypothesized that timed light therapy might reverse disrupted circadian rhythms and glucose intolerance observed among r-NSWs). METHODS: R-NSWs were randomly assigned to a protocol that included 12 weeks on followed by 12 weeks off light therapy (n = 13; 6 men; mean age, 39.5 ± 7.3 years) or a no-treatment control group (n = 9; 3 men; mean age 41.7 ± 6.3 years). Experimental and control participants underwent identical metabolic evaluations that included anthropometric, metabolic (including oral glucose tolerance tests), lipid, and inflammation-associated parameters together with an assessment of sleep quality and expression of circadian transcription factors REV-ERBα and BMAL1 in peripheral blood mononuclear cells (PBMCs) at baseline, 12 weeks, and 24 weeks of the protocol. RESULTS: Twelve weeks of warm white-light exposure (10,000 lx at 35 cm for 30 min per day) had no impact on sleep, metabolic, or inflammation-associated parameters among r-NSWs in the experimental group. However, our findings revealed significant decreases in REV-ERBα gene expression (p = 0.048) and increases in the REV-ERBα/BMAL1 ratio (p = 0.040) compared to baseline in PBMCs isolated from this cohort. Diminished expression of REV-ERBα persisted, although the REV-ERBα/BMAL1 ratio returned to baseline levels after the subsequent 12-day wash-out period. CONCLUSIONS: Our results revealed that intermittent light therapy had no impact on inflammatory parameters or glucose tolerance in a defined cohort of r-NSWs. However, significant changes in the expression of circadian clock genes were detected in PBMCs of these subjects undergoing light therapy.

Atrial fibrillation and risk of progressive heart failure in patients with preserved ejection fraction heart failure.

AIMS: Understanding of the pathophysiology of progressive heart failure (HF) in patients with heart failure with preserved ejection fraction (HFpEF) is incomplete. We sought to identify factors differentially associated with risk of progressive HF death and hospitalization in patients with HFpEF compared with patients with HF and reduced ejection fraction (HFrEF). METHODS AND RESULTS: Prospective cohort study of patients newly referred to secondary care with suspicion of HF, based on symptoms and signs of HF and elevated natriuretic peptides (NP), followed up for a minimum of 6 years. HFpEF and HFrEF were diagnosed according to the 2016 European Society of Cardiology guidelines. Of 960 patients referred, 467 had HFpEF (49%), 311 had HFrEF (32%), and 182 (19%) had neither. Atrial fibrillation (AF) was found in 37% of patients with HFpEF and 34% with HFrEF. During 6 years follow-up, 19% of HFrEF and 14% of HFpEF patients were hospitalized or died due to progressive HF, hazard ratio (HR) 0.67 (95% CI: 0.47-0.96; P = 0.028). AF was the only marker that was differentially associated with progressive HF death or hospitalization in patients with HFpEF HR 2.58 (95% CI: 1.59-4.21; P < 0.001) versus HFrEF HR 1.11 (95% CI: 0.65-1.89; P = 0.7). CONCLUSIONS: De novo patients diagnosed with HFrEF have greater risk of death or hospitalization due to progressive HF than patients with HFpEF. AF is associated with increased risk of progressive HF death or hospitalization in HFpEF but not HFrEF, raising the intriguing possibility that this may be a novel therapeutic target in this growing population.

Rapid adaptive radiation of Darwin's finches depends on ancestral genetic modules.

Recent adaptive radiations are models for investigating mechanisms contributing to the evolution of biodiversity. An unresolved question is the relative importance of new mutations, ancestral variants, and introgressive hybridization for phenotypic evolution and speciation. Here, we address this issue using Darwin's finches and investigate the genomic architecture underlying their phenotypic diversity. Admixture mapping for beak and body size in the small, medium, and large ground finches revealed 28 loci showing strong genetic differentiation. These loci represent ancestral haplotype blocks with origins predating speciation events during the Darwin's finch radiation. Genes expressed in the developing beak are overrepresented in these genomic regions. Ancestral haplotypes constitute genetic modules for selection and act as key determinants of the unusual phenotypic diversity of Darwin's finches. Such ancestral haplotype blocks can be critical for how species adapt to environmental variability and change.

Instrument tables equipped with local unidirectional airflow units reduce bacterial contamination during orthopedic implant surgery in an operating room with a displacement ventilation system.

Background: Airborne bacteria present in the operating room may be a cause of surgical site infection, either contaminating the surgical wound directly, or indirectly via e.g. surgical instruments. The aim of this study was to evaluate if instrument and assistant tables equipped with local unidirectional airflow reduce bacterial contamination of the instrument area to ultra clean levels, during orthopedic implant surgery in an operating room with displacement ventilation. Methods: Local airflow units of instrument and assistant tables were either active or inactive. Colony forming units were sampled intraoperatively from the air above the instruments and from instrument dummies. A minimum of three air samples and two-three samples from instrument dummies were taken during each surgery. Samples were incubated on agar for total aerobic bacterial count. The mean air and instrument contamination during each surgery was calculated and used to analyze the difference in contamination depending on use of local airflow or not. All procedures were performed in the same OR. Results: 188 air and 124 instrument samples were collected during 48 orthopedic implant procedures. Analysis showed that local unidirectional airflow above the surgical instruments significantly reduced the bacterial count in the air above assistant table (P<0.001) and instrument table (P=0.002), as well as on the instrument dummies from the assistant table (P=0.001). Conclusions: Instrumentation tables equipped with local unidirectional airflow protect the surgical instruments from bacterial contamination during orthopedic implant surgery and may therefore reduce the risk of indirect wound contamination.

Traumatic Pediatric Tracheal Rupture After Blunt Force Sporting Injury: Case Report and Review of the Literature.

OBJECTIVE: This paper presents the case of a traumatic tracheal rupture in a pediatric patient. The body of literature of the clinical features, evaluation, and management of this uncommon presentation is discussed. CASE: A 13-year-old boy sustained an intrathoracic tracheal rupture whilst playing Australian Rules football. He developed hallmark clinical features of air extravasation and was intubated prior to transfer to a tertiary pediatric center for further management. After a short trial of conservative management, his respiratory status deteriorated and he was taken to the operating theater for open surgical repair of the defect. CONCLUSION: Traumatic rupture of the trachea is a rare injury in children. This case demonstrates the dynamic nature of this serious injury and the need for multidisciplinary care in achieving the optimal outcome.

Efficacy of dexamethasone in the management of malignant small bowel obstruction in advanced epithelial ovarian cancer.

INTRODUCTION: Malignant small bowel obstruction (MSBO) occurs in up to 50% of women with advanced epithelial ovarian cancer (EOC) causing symptom burden and distress to women and their families, particularly in the terminal stages of the disease. Corticosteroids are used to promote symptom resolution in malignant small bowel obstruction (MSBO) related to EOC, with little published data on their efficacy, optimal dosing and duration of treatment. OBJECTIVE: To evaluate the efficacy of dexamethasone in achieving symptom control in women with advanced EOC presenting with MSBO, assess dexamethasone dosing and efficacy over subsequent presentations, and examine differences in dexamethasone responsiveness between platinum-resistant and platinum-sensitive patient. METHODS: This is a retrospective cohort study of women presenting with MSBO due to advanced EOC over a 12-year period from January 2005 to December 2016 in a single tertiary hospital. RESULTS: Ninety-one women with MSBO were administered dexamethasone over 154 admissions with 89% of women initially achieving partial or complete symptom control. Dexamethasone responsiveness did not change with recurrent admissions, and platinum responsive patients were more likely to respond to dexamethasone than platinum-resistant patients (OR 3.6 [95%CI 1.1 to 12.2, p = 0.04]). A total of 15.6% of patients required additional measures to control symptoms of MSBO, and 44.8% had adequate symptom resolution to allow them to remain on or commence further treatment for EOC. CONCLUSION: Dexamethasone therapy is a useful adjunctive therapy in the management of symptoms associated with MSBO in women with EOC.

Genetic and transcriptomic analyses support a switch to lytic phase in Epstein Barr virus infection as an important driver in developing Systemic Lupus Erythematosus.

To investigate the molecular mechanisms through which Epstein-Barr virus (EBV) may contribute to Systemic Lupus Erythematosus (SLE) pathogenesis, we interrogated SLE genetic risk loci for signatures of EBV infection. We first compared the gene expression profile of SLE risk genes across 459 different cell/tissue types. EBV-infected B cells (LCLs) had the strongest representation of highly expressed SLE risk genes. By determining an SLE risk allele effect on gene expression (expression quantitative trait loci, eQTL) in LCLs and 16 other immune cell types, we identified 79 SLE risk locus:gene pairs putatively interacting with EBV infection. A total of 10 SLE risk genes from this list (CD40, LYST, JAZF1, IRF5, BLK, IKZF2, IL12RB2, FAM167A, PTPRC and SLC15A) were targeted by the EBV transcription factor, EBNA2, differentially expressed between LCLs and B cells, and the majority were also associated with EBV DNA copy number, and expression level of EBV encoded genes. Our final gene network model based on these genes is suggestive of a nexus involving SLE risk loci and EBV latency III and B cell proliferation signalling pathways. Collectively, our findings provide further evidence to support the interaction between SLE risk loci and EBV infection that is in part mediated by EBNA2. This interplay may increase the tendency towards EBV lytic switching dependent on the presence of SLE risk alleles. These results support further investigation into targeting EBV as a therapeutic strategy for SLE.

Evaluating patient-reported symptoms and late adverse effects following completion of first-line chemotherapy for ovarian cancer using the MOST (Measure of Ovarian Symptoms and Treatment concerns).

OBJECTIVES: Knowledge on the course of symptoms patients with ovarian cancer experience is limited. We documented the prevalence and trajectories of symptoms after first-line chemotherapy using the Measure of Ovarian Symptoms and Treatment concerns (MOST). METHODS: A total of 726 patients who received platinum-based chemotherapy for ovarian cancer were asked to complete the MOST every 3 months, beginning 6 months post-diagnosis and continuing for up to 4 years. We used descriptive statistics to examine temporal changes in MOST-S26 index scores for disease or treatment-related (MOST-DorT), neurotoxicity (MOST-NTx), abdominal (MOST-Abdo), and psychological (MOST-Psych) symptoms, and wellbeing (MOST-Wellbeing) and selected individual symptoms. We used group-based trajectory models to identify groups with persistently poor symptoms. RESULTS: The median MOST-Abdo, MOST-DorT and MOST-Wellbeing score were worst at chemotherapy-end but improved and stabilised by 1, 3 and 12 months after treatment, respectively. The median MOST-NTx score peaked at 1 month after treatment before improving, while the median MOST-Psych score did not change substantially over time. Long-term moderate-to-severe fatigue (32%), trouble sleeping (31%), sore hands and feet (21%), pins and needles (20%) and anxiety (18%) were common. Trajectory models revealed groups of patients with persistent symptoms had MOST-DorT scores above 30 and MOST-NTx scores above 40 at treatment-end. CONCLUSIONS: Although many patients report improvements in symptoms by 3 months after first-line chemotherapy for ovarian cancer, patients who score > 30/100 on MOST-S26-DorT or > 40/100 on MOST-S26-NTx at the end of chemotherapy are likely to have persistent symptoms. The MOST could triage this at-risk subset for early intervention.