Unsupervised machine learning highlights the challenges of subtyping disorders of gut-brain interaction.

BACKGROUND: Unsupervised machine learning describes a collection of powerful techniques that seek to identify hidden patterns in unlabeled data. These techniques can be broadly categorized into dimension reduction, which transforms and combines the original set of measurements to simplify data, and cluster analysis, which seeks to group subjects based on some measure of similarity. Unsupervised machine learning can be used to explore alternative subtyping of disorders of gut-brain interaction (DGBI) compared to the existing gastrointestinal symptom-based definitions of Rome IV. PURPOSE: This present review aims to familiarize the reader with fundamental concepts of unsupervised machine learning using accessible definitions and provide a critical summary of their application to the evaluation of DGBI subtyping. By considering the overlap between Rome IV clinical definitions and identified clusters, along with clinical and physiological insights, this paper speculates on the possible implications for DGBI. Also considered are algorithmic developments in the unsupervised machine learning community that may help leverage increasingly available omics data to explore biologically informed definitions. Unsupervised machine learning challenges the modern subtyping of DGBI and, with the necessary clinical validation, has the potential to enhance future iterations of the Rome criteria to identify more homogeneous, diagnosable, and treatable patient populations.

Plasma soluble fms-like tyrosine kinase-1, placental growth factor, and vascular endothelial growth factor system gene variants as predictors of survival in heart failure.

AIMS: Soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF), components of the vascular endothelial growth factor (VEGF) system, play key roles in angiogenesis. Reports of elevated plasma levels of sFlt-1 and PlGF in coronary heart disease and heart failure (HF) led us to investigate their utility, and VEGF system gene single nucleotide polymorphisms (SNPs), as prognostic biomarkers in HF. METHODS AND RESULTS: ELISA assays for sFlt-1, PlGF and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were performed on baseline plasma samples from the PEOPLE cohort (n = 890), a study of outcomes among patients after an episode of acute decompensated HF. Eight SNPs potentially associated with sFlt-1 or PlGF levels were genotyped. sFlt-1 and PlGF were assayed in 201 subjects from the Canterbury Healthy Volunteers Study (CHVS) matched to PEOPLE participants. All-cause death was the major endpoint for clinical outcome considered. In PEOPLE participants, mean plasma levels for both sFlt-1 (125 ± 2.01 pg/ml) and PlGF (17.5 ± 0.21 pg/ml) were higher (both p < 0.044) than in the CHVS cohort (81.2 ± 1.31 pg/ml and 15.5 ± 0.32 pg/ml, respectively). sFlt-1 was higher in HF with reduced ejection fraction compared to HF with preserved ejection fraction (p = 0.005). The PGF gene SNP rs2268616 was univariately associated with death (p = 0.016), and was also associated with PlGF levels, as was rs2268614 genotype. Cox proportional hazards modelling (n = 695, 246 deaths) showed plasma sFlt-1, but not PlGF, predicted survival (hazard ratio 6.44, 95% confidence interval 2.57-16.1; p < 0.001) in PEOPLE, independent of age, NT-proBNP, ischaemic aetiology, diabetic status and beta-blocker therapy. CONCLUSIONS: Plasma sFlt-1 concentrations have potential as an independent predictor of survival and may be complementary to established prognostic biomarkers in HF.

Clinical and functional outcomes of TKA after HTO or UKA: a New Zealand Joint Registry Study.

INTRODUCTION: Surgical options for patients with unicompartmental knee osteoarthritis include high tibial osteotomy (HTO) or unicompartmental knee arthroplasty (UKA). When managing younger patients with a higher chance of further surgery, the outcome of any subsequent conversion to total knee arthroplasty (TKA) also needs to be considered. The aim of this study was to compare implant survivorship and patient-reported outcomes for patients undergoing TKA after previous HTO or UKA, with comparisons for age, gender and comorbidities. METHODS: Revision risk and 6-month Oxford Knee Scores (OKS) from the New Zealand Joint Registry were compared for patients who underwent TKA after HTO (HTO-TKA; n = 1556) or UKA (UKA-TKA; n = 965) between 1999 and 2019, with a comparison group of primary TKA (n = 110,948). Mean follow-up was 8.2 years. RESULTS: Adjusted revision risk was similar for HTO-TKA and UKA-TKA groups (hazard ratio (HR) 1.04, p = 0.84); and risk for both groups were higher than primary TKA (HTO-TKA HR 1.45, p = 0.002; UKA-TKA HR 1.51, p = 0.01). Overall adjusted mean OKS at 6 months for HTO-TKA (36.2) was similar to primary TKA (36.8, p = 0.23); and both were higher than UKA-TKA (34.2, p < 0.001). For the youngest patient group (< 55 years), revision rates of UKA-TKA were two-fold higher than HTO-TKA (2.8 vs. 1.3 per 100 component yrs, p < 0.03). HTO-TKA had better OKS (37.5 vs. 34.1, p < 0.0001) for males. Mean OKS for UKA-TKA was lower than HTO-TKA for patients with ASA 1-2 (35.6 vs. 37.5, p < 0.01). CONCLUSION: The findings from this study suggest that revision rate following TKA after HTO and UKA are similar. However, TKA after HTO have superior functional outcomes compared with TKA after UKA and are comparable to functional outcomes post primary TKA. The results support the use of HTO for young, male and less co-morbid patients.

Convalescent Growth Differentiation Factor-15 and Long-Term Outcomes after an Acute Coronary Syndrome.

BACKGROUND: Growth differentiation factor-15 (GDF-15) has been shown to be associated with adverse clinical outcomes in patients after an acute coronary syndrome when measured soon after an event. Although dynamic in the acute phase after myocardial injury, GDF-15 has been shown to remain stable during convalescence. In this study, we aimed to assess the value of GDF-15 as a long-term prognostic marker for clinical outcomes when measured in the convalescent phase following an acute coronary syndrome. METHODS: GDF-15 concentrations were measured in 1945 patients who were recruited between 2002 and 2009 to the Coronary Disease Cohort Study. For this analysis, follow-up was curtailed at 10 years and association of GDF-15 with all-cause death, cardiovascular death, recurrent myocardial infarction, and heart failure hospitalizations were assessed with multivariate Cox proportional hazard regression analysis. RESULTS: After 10 years of follow-up, there were 648 deaths (348 from cardiovascular causes), 500 admissions for myocardial infarction, and 436 for heart failure. Four-month convalescent GDF-15 demonstrated a robust independent association with all endpoints, which remained after adjustment for Global Registry of Acute Coronary Events score and other convalescent biomarkers. When compared to the lowest quartile of GDF-15 concentrations, those in the highest quartile had a 3-fold increased risk of all-cause death. CONCLUSIONS: Convalescent plasma GDF-15 is a strong and independent predictor of 10-year all-cause death, cardiovascular death, recurrent myocardial infarction, and heart failure admission following an acute coronary syndrome. AUSTRALIAN NEW ZEALAND CLINICAL TRIALS REGISTRY TRIAL ID: ACTRN12605000431628.

Reverse total shoulder arthroplasty for acute proximal humeral fracture has comparable 10-year outcomes to elective indications: results from the New Zealand Joint Registry.

HYPOTHESIS AND BACKGROUND: Recently, the indication of reverse total shoulder arthroplasty (RTSA) has expanded beyond rotator cuff arthropathy to include treatment of complex acute proximal humeral fracture (PHF). Limited previous studies have compared the long-term clinical and functional outcomes of patients undergoing RTSA for PHF vs. elective indications for degenerative conditions. The purpose of this study was to compare implant survivorship, reasons for revision and functional outcomes in patients undergoing RTSA for acute PHF with those undergoing elective RTSA in a population-based cohort study. METHODS: Prospectively collected data from the New Zealand Joint Registry from 1999 to 2021 and identified 6862 patients who underwent RTSA. Patients were categorized by preoperative indication, including PHF (10.8%), rotator cuff arthropathy (RCA) (44.5%), osteoarthritis (OA) (34.1%), rheumatoid arthritis (RA) (5.5%), and old traumatic sequelae (5.1%). Revision-free implant survival and functional outcomes (Oxford Shoulder Scores [OSSs] at the 6-month, 5-year, and 10-year follow-ups) were adjusted by age, sex, American Society of Anesthesiologists class, and surgeon experience and compared. RESULTS: Revision-free implant survival at 10 years for RTSA for PHF was 97.3%, compared with 96.1%, 93.7%, 92.8%, and 91.3% for OA, RCA, RA and traumatic sequelae, respectively. When compared with RTSA for PHF, the adjusted risk of revision was significantly higher for traumatic sequelae (hazard ratio = 2.3, P = .023) but not for other elective indications. The most common reason for revision in the PHF group was dislocation or instability (42.9%), which was similar to the OA (47.6%) and traumatic sequelae (33.3%) groups. At 6 months post-surgery, OSSs were significantly lower for the PHF group compared with the RCA, OA, and RA groups (31.1 vs. 35.6, 37.7, and 36.5, respectively, P < .001), and similar to traumatic sequelae (31.7, P = .431). At 5 years, OSSs were only significantly lower for PHF compared with OA (37.4 vs. 41.0, P < .001) and there was no difference between the PHF and other groups. At 10 years, there were no significant differences between groups. CONCLUSIONS: RTSA for PHF demonstrated reliable long-term survivorship and functional outcomes compared with elective indications. Despite lower functional outcomes in the early postoperative period for the PHF group, implant survivorship was similar in patients undergoing RTSA for the primary indication of acute PHF compared with RCA, OA, and RA and superior compared to the primary indication of traumatic sequelae.

Cardiac effects of myoregulin in ischemia-reperfusion.

Myoregulin is a recently discovered micropeptide that controls calcium levels by inhibiting the intracellular calcium pump sarco-endoplasmic reticulum Ca2+-ATPase (SERCA). Keeping calcium levels balanced in the heart is essential for normal heart functioning, thus myoregulin has the potential to be a crucial regulator of cardiac muscle performance by reducing the rate of intracellular Ca2+ uptake. We provide the first report of myoregulin mRNA expression in human heart tissue, absence of expression in human plasma, and the effects of myoregulin on cardiac hemodynamics in an ex vivo Langendorff isolated rat heart model of ischemia/reperfusion. In this preliminary study, myoregulin provided a cardio-protective effect, as assessed by preservation of left ventricular contractility and relaxation, during ischemia/reperfusion. This study provides the foundation for future research in this area.

The Epidemiology of Inflammatory Bowel Disease in Oceania: A Systematic Review and Meta-Analysis of Incidence and Prevalence.

BACKGROUND: Past studies have shown high rates of inflammatory bowel disease (IBD) in Australia and New Zealand (NZ). We aimed to describe the epidemiology of IBD in Australia, NZ, and the surrounding region (collectively termed Oceania) by conducting a systematic review and meta-analysis. METHODS: Electronic databases were searched from inception to April 2023 for studies reporting incidence or prevalence rates of IBD, Crohn's disease (CD), or ulcerative colitis (UC) in Oceania. All study designs were included. A meta-analysis calculated pooled estimates of incidence and prevalence, and a sensitivity analysis compared the pooled population-based studies with the non-population-based studies and the Australian and NZ studies separately. RESULTS: Nineteen incidence and 11 prevalence studies were included; 2 studies were from the Pacific Islands, with the rest coming from Australia and NZ. Pooled estimates showed high incidence rates of 19.8 (95% confidence interval [CI], 15.8-23.7) for IBD, 8.3 (95% CI, 6.9-9.8) for CD, and 7.4 (95% CI, 5.7-9.1) for CD per 100 000 person-years. CD was more common than UC in most studies. The pooled estimates for the prevalence studies were 303.3 (95% CI, 128.1-478.4) for IBD, 149.8 (95% CI, 71.0-228.5) for CD, and 142.2 (95% CI, 63.1-221.4) for UC per 100 000 persons. Studies using population-based data collection methods showed higher pooled rates for both incidence and prevalence. CONCLUSIONS: The incidence and prevalence of IBD in Oceania is high. The studies were heterogeneous and there were several geographic areas with no information, highlighting the need for more epidemiological studies of IBD.

This systematic review and meta-analysis of inflammatory bowel disease in Oceania found high incidence rates (19.8 [95% confidence interval, 15.8-23.7] per 100 000 person-years) and prevalence rates (303.3 [95% confidence interval, 128.1-478.4] per 100 000 persons). Most studies were from Australasia, with only 2 from the Pacific Islands.

The Disease Severity Index for Inflammatory Bowel Disease Is a Valid Instrument that Predicts Complicated Disease.

BACKGROUND: The disease severity index (DSI) for inflammatory bowel disease (IBD) combines measures of disease phenotype, inflammatory activity, and patient-reported outcomes. We aimed to validate the DSI and assess its utility in predicting a complicated IBD course. METHODS: A multicenter cohort of adults with IBD was recruited. Intraclass correlation coefficients (ICCs) and weighted Kappa assessed inter-rater reliability. Cronbach's alpha measured internal consistency of DSI items. Spearman's rank correlations compared the DSI with endoscopic indices, symptom indices, quality of life, and disability. A subgroup was followed for 24 months to assess for a complicated IBD course. Area under the receiver operating characteristics curve (AUROC) and multivariable logistic regression assessed the utility of the DSI in predicting disease progression. RESULTS: Three hundred and sixty-nine participants were included (Crohn's disease [CD], n = 230; female, n = 194; mean age, 46 years [SD, 15]; median disease duration, 11 years [interquartile range, 5-21]), of which 171 (CD, n = 99; ulcerative colitis [UC], n = 72) were followed prospectively. The DSI showed inter-rater reliability for CD (ICC 0.93, n = 65) and UC (ICC 0.97, n = 33). The DSI items demonstrated inter-rater agreement (Kappa > 0.4) and internal consistency (CD, α > 0.59; UC, α > 0.75). The DSI was significantly associated with endoscopic activity (CDn=141, r = 0.65, P < .001; UCn=105, r = 0.80, P < .001), symptoms (CDn=159, r = 0.69, P < .001; UCn=132, r = 0.58, P < .001), quality of life (CDn=198, r = -0.59, P < .001; UCn=128, r = -0.68, P < .001), and disability (CDn=83, r = -0.67, P < .001; UCn=52, r = -0.74, P < .001). A DSI of 23 best predicted a complicated IBD course (AUROC = 0.82, P < .001) and was associated with this end point on multivariable analyses (aOR, 9.20; 95% confidence interval, 3.32-25.49). CONCLUSIONS: The DSI reliably encapsulates factors contributing to disease severity and accurately prognosticates the longitudinal IBD course.

This study shows that the disease severity index (DSI) for inflammatory bowel disease (IBD) is a valid and reliable instrument encapsulating the disease phenotype, disease activity, and impact of the disease on the patient; and it accurately predicts for incident disease complications.

Is MRI screening for bone marrow oedema useful in predicting lumbar bone stress injuries in adult male professional cricketers? A New Zealand pilot study.

OBJECTIVES: The aims were to (1) prospectively observe the incidence of bone marrow oedema in asymptomatic adult male domestic professional cricketers during a season and evaluate its relationship to the development of lumbar bone stress injury and (2) further understand the practicalities of implementing a Magnetic Resonance Imaging-based screening program to prevent lumbar bone stress injury in New Zealand cricket. DESIGN: Prospective observational cohort. METHODS: Adult male pace bowlers received 6-weekly pre-planned Magnetic Resonance Imaging scans over a single season to determine the presence and intensity of bone marrow oedema in the posterior vertebral arches of the lumbar spine. The participants bowling volume and back pain levels were monitored prospectively. RESULTS: 22 participants (mean age 25.3 years (range 20-32 years)) completed all 4 scans. Ten participants had a prior history of lumbar bone stress injury. Ten participants (45 %, 95 % confidence interval 24-68 %) had bone marrow oedema evident on at least one scan, with 9 (41 %) participants recording a bone marrow oedema intensity ≥ 2 and 5 (23 %) participants demonstrated an intensity ≥ 3. During the study one participant was diagnosed with a lumbar bone stress reaction. No participants developed a lumbar bone stress fracture. CONCLUSIONS: Due to the lower incidence of lumbar bone stress injuries in adult bowlers coupled with uncertainty over appropriate threshold values for bone marrow oedema intensity, implementation of a resource intense screening program aimed at identifying adult domestic cricketers at risk of developing a lumbar bone stress injury is not currently supported.

Descriptive Epidemiology of Pediatric Inflammatory Bowel Disease in Oceania: A Systematic Review and Meta-Analysis.

OBJECTIVES: Pediatric inflammatory bowel diseases (IBDs) are chronic, idiopathic illnesses of the digestive tract, which can impact adversely on children's quality of life and burden health systems. International studies have shown these diseases are increasing. The aim was to describe pediatric IBD epidemiology across Oceania by conducting a systematic review and meta-analysis of incidence and prevalence. METHODS: Medline, EMBASE and Web of Science databases were searched in October 2022 for studies reporting rates of IBD, Crohn disease (CD), or ulcerative colitis (UC) in children (≤19 years). Several data collection methodologies were included and pooled estimates of incidence and prevalence were calculated using a random effects model with I2 measures of heterogeneity. RESULTS: Nineteen articles provided 15 incidence and 7 prevalence studies. Fourteen studies were from Australia, 8 studies from New Zealand, and no studies were found from the Pacific Islands. Study dates ranged from 1950 to 2020 with 11 studies using population-based designs. Pooled estimates for annual incidence were IBD 4.1 (3.4-4.8, I2 = 98.7), CD 2.3 (1.9-2.7, I2 = 98.6), and UC 0.9 (0.6-1.1, I2 = 96.8) per 100,000 person-years. Prevalence rates were IBD 36.0 (23.5-48.5, I2 = 98.4), CD 23.2 (6.6-39.8, I2 = 97.8), and UC 7.6 (2.7-12.5, I2 = 99.6) per 100,000 persons. CONCLUSIONS: Pediatric IBD is prevalent in Oceania with high incidence rates, particularly for CD. Low rates of IBD were observed in indigenous Australian, Maori, and New Zealand Pacific children and there were no studies from the Pacific Islands highlighting this as an area in need of further research.

The Strongest Oxford Knee Score Predictors of Subsequent Revision are "Overall Pain," "Limping When Walking," and "Knee Giving Way".

BACKGROUND: The Oxford Knee Score (OKS) is used to measure knee arthroplasty outcomes; however, it is unclear which questions are more relevant. Our aims were to (1) identify which OKS question(s) were the strongest predictors of subsequent revision and (2) compare the predictive ability of the "pain" and "function" domains. METHODS: All primary total knee arthroplasties (TKAs) and unicompartmental knee arthroplasties (UKAs) in the New Zealand Joint Registry between 1999 and 2019 with an OKS at 6 months (TKA n = 27,708; UKA n = 8,415), 5 years (TKA n = 11,519; UKA n = 3,365) or 10 years (TKA n = 6,311; UKA n = 1,744) were included. Prediction models were assessed using logistic regressions and receiver operating characteristic analyses. RESULTS: A reduced model with 3 questions ("overall pain," "limping when walking," "knee giving way") showed better diagnostic ability than full OKS for predicting UKA revision at 6 months (area under the curve [AUC]: 0.80 versus 0.78; P < .01) and 5 years (0.81 versus 0.77; P = .02), and comparable diagnostic ability for predicting TKA revision at all time points (6 months, 0.77 versus 0.76; 5 years, 0.78 versus 0.75; 10 years, 0.76 versus 0.73; all not significant), and UKA revision at 10 years (0.80 versus 0.77; not significant). The pain domain had better diagnostic ability for predicting subsequent revision for both procedures at 5 and 10 years. CONCLUSION: Questions on "overall pain", "limping when walking", and "knee giving way" were the strongest predictors of subsequent revision. Attention to low scores from these questions during follow-up may allow for prompt identification of patients most at risk of revision.

Short-term outcomes following 159 stemmed pyrolytic carbon shoulder hemiarthroplasties and how they compare with conventional hemiarthroplasties and total shoulder arthroplasties in patients younger than 60 years with osteoarthritis: results from the New Zealand National Joint Registry.

BACKGROUND: Despite the increasing use of pyrolytic carbon (pyrocarbon) hemiarthroplasty (PyCHA), clinical data reporting on its outcomes remain scarce. To date, no studies have compared the outcomes of stemmed PyCHA vs. conventional hemiarthroplasty (HA) and anatomic total shoulder arthroplasty (aTSA) in young patients. The primary aim of this study was to report on the outcomes of the first 159 stemmed PyCHAs performed in New Zealand. The secondary aim was to compare the outcomes of stemmed PyCHA vs. HA and aTSA in patients aged <60 years with osteoarthritis. We hypothesized that stemmed PyCHA would be associated with a low revision rate. We further hypothesized that in young patients, PyCHA would be associated with a lower revision rate and superior functional outcomes compared with HA and aTSA. METHODS: Data from the New Zealand National Joint Registry were used to identify patients who underwent PyCHA, HA, and aTSA between January 2000 and July 2022. The total number of revisions in the PyCHA group was determined, and the indications for surgery, reasons for revision, and types of revision were recorded. In patients aged <60 years, a matched-cohort analysis was performed comparing functional outcomes using the Oxford Shoulder Score (OSS). The revision rate of PyCHA was compared with that of HA and aTSA, calculated as revisions per 100 component-years. RESULTS: In total, 159 cases of stemmed PyCHA were performed and 5 cases underwent revision, resulting in an implant retention rate of 97%. Among patients aged <60 years with shoulder osteoarthritis, 48 underwent PyCHA compared with 150 who underwent HA and 550 who underwent aTSA. Patients treated with aTSA had a superior OSS compared with PyCHA and HA patients. The difference in the OSS between the aTSA and PyCHA groups exceeded the minimal clinically important difference of 4.3. There was no difference in revision rates between the groups. CONCLUSIONS: This study represents the largest cohort of patients treated with PyCHA and is the first to compare stemmed PyCHA with HA and aTSA in young patients. In the short term, PyCHA appear to be a promising implant with an excellent implant retention rate. In patients aged <60 years, the revision rate is comparable between PyCHA and aTSA. However, aTSA remains the implant of choice to optimize early postoperative function. Further studies are required to elucidate the long-term outcomes of PyCHA, particularly how they compare with those of HA and aTSA in young patients.

Associations of the Oxford Knee Score and knee arthroplasty revision at long-term follow-up.

BACKGROUND: Self-reported outcome measures are increasingly being collected for healthcare evaluation therefore it is prudent to understand their associations with patient outcomes. Our aims were to investigate: (1) if Oxford Knee Score (OKS) is associated with impending revision at long-term (5 and 10 years) follow-up, and (2) if decreased OKS at subsequent follow-ups is associated with higher risk of revision. PATIENTS AND METHODS: All total knee (TKAs) and unicompartmental knee arthroplasties (UKAs) between 1999 and 2019 in the New Zealand Joint Registry with an OKS at 6 months (TKA n = 27 708, UKA n = 8415), 5 years (TKA n = 11 519, UKA n = 3365) or 10 years (TKA n = 6311, UKA n = 1744) were included. Logistic regression determined associations of the OKS with revision within 2 years of each score. Change in OKS between timepoints were compared with revision risk. RESULTS: For every one-unit increase in OKS, the odds of TKA and UKA revision decreased by 10% and 11% at 6 months, 10% and 12% at 5 years and 9% and 5% at 10 years. For both procedures a decrease of seven or more OKS points from previous follow-up was associated with higher risk of revision (5 years: TKA 4.7% versus 0.5%, UKA 8.7% versus 0.9%; 10 years: TKA 4.4% versus 0.7%, UKA 11.3% versus 1.5%; all P < 0.01). CONCLUSION: The OKS had a strong negative association with risk of impending TKA and UKA revision from early to long-term (10+ years) follow-up. A decrease of seven or more points when compared with the previous follow-up was also associated with higher revision risk.

Comparative Study of ACL Reconstruction With Hamstring Versus Patellar Tendon Graft in Young Women: A Cohort Study From the New Zealand ACL Registry.

BACKGROUND: Young female athletes are a specific population that is at high risk of primary anterior cruciate ligament (ACL) rupture and subsequent graft failure. Despite large numbers of ACL reconstructions being carried out in young women, there is limited analysis of outcomes in this group, leading to low levels of evidence for graft choice. PURPOSE: To assess the effect of graft choice on ACL reconstruction failure rates among young women in New Zealand. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Prospective data captured by the New Zealand ACL Registry between April 2014 and March 2022 were reviewed. Young women aged 15 to 20 years were included. The primary outcome measure was ACL graft failure during the study period, with the key independent variable being graft type, either patellar or hamstring tendon autograft. This is presented as the rate per 100 patient-years and is compared between the 2 groups using the hazard ratio generated from a Cox proportional hazards regression. Secondary outcome measures were Marx activity scores and the Knee injury and Osteoarthritis and Outcome Score patient-reported outcome measure. RESULTS: A total of 1261 primary ACL reconstructions in young women aged 15 to 20 years were reviewed. Hamstring tendon grafts were used in 797 (63%) reconstructions and patellar tendon graft in 464 (37%) reconstructions. Patients with a hamstring tendon graft had a graft failure rate of 7.7% compared with 1.1% in patients with a patellar tendon graft (hazard ratio, 6.1; 95% CI, 2.4-15.1; P < .001). The number of failures per 100 person-years was significantly higher in the hamstring group (2.05) compared with the patellar tendon group (0.37). No difference was noted at final follow-up between the hamstring tendon and patellar tendon groups when comparing patient-reported outcome measures during the follow-up period. CONCLUSION: In the young female population of this study, the use of a patellar tendon graft was associated with reduced risk of graft failure and was not associated with an increase in knee morbidity. This highlights the importance of informed decision-making in this high-risk population when considering ACL reconstruction graft type.

Predictors of Intensive Care Admission in Hypoxemic Bronchiolitis Infants, Secondary Analysis of a Randomized Trial.

OBJECTIVES: To evaluate in a preplanned secondary analysis of our parent randomized controlled trial predictors of intensive care unit (ICU) admission in infants with bronchiolitis and analyze if these predictors are equally robust for children receiving high-flow or standard-oxygen. STUDY DESIGN: A secondary analysis of a multicenter, randomized trial of infants aged <12 months with bronchiolitis and an oxygen requirement was performed using admission and outcome data of all 1472 enrolled infants. The primary outcome was ICU admission. The predictors evaluated were baseline characteristics including physiological data and medical history. RESULTS: Of the 1472 enrolled infants, 146 were admitted to intensive care. Multivariate predictors of ICU admission were age (weeks) (OR: 0.98 [95% CI: 0.96-0.99]), pre-enrolment heart rate >160/min (OR: 1.80 [95% CI: 1.23-2.63]), pre-enrolment SpO2 (transcutaneous oxygen saturation) (%) (OR: 0.91 [95% CI: 0.86-0.95]), previous ICU admission (OR: 2.16 [95% CI: 1.07-4.40]), and time of onset of illness to hospital presentation (OR: 0.78 [95% CI: 0.65-0.94]). The predictors were equally robust for infants on high-flow nasal cannula therapy or standard-oxygen therapy. CONCLUSION: Age <2 months, pre-enrolment heart rate >160/min, pre-enrolment SpO2 of <87%, previous ICU admission and time of onset of ≤2 days to presentation are predictive of an ICU admission during the current hospital admission of infants with bronchiolitis independent of oxygenation method used. TRIAL REGISTRATION: ACTRN12613000388718.

The Impact of Disease Activity on Sexual and Erectile Dysfunction in Patients With Inflammatory Bowel Disease.

BACKGROUND: Increased disease activity may be a risk factor for sexual dysfunction (SD) in patients with inflammatory bowel disease (IBD). This study investigated associations between objective measures of disease activity and sexual function. METHODS: Adults with IBD undergoing ileocolonoscopy were prospectively recruited. Demographic, sexual function (Female Sexual Function Index and International Index of Erectile Function), disease activity (endoscopic, biomarker, and symptoms), psychological symptoms, and quality-of-life data were collected. Rates of SD and erectile dysfunction (ED) were compared between patients with active and inactive inflammation and symptoms using the Fisher's exact test. Logistic regression examined associations between SD and ED, and disease characteristics and psychological symptoms. RESULTS: A total of 159 participants were included, 97 had Crohn's disease and 85 were women. SD was reported in 36 of 59 and 13 of 59 sexually active women and men, respectively and ED in 22 of 59 sexually active men. Rates of SD and ED were similar between individuals with active and inactive IBD based on endoscopic indices (P > .05) and biomarkers (P > .05). Women with active IBD symptoms experienced significantly higher rates of SD (P < .05), but men did not (P > .05). Multivariable logistic regression identified that symptoms of severe depression (odds ratio, 5.77; 95% confidence interval, 1.59-20.94) were associated with SD in women, and severe anxiety (odds ratio, 15.62; 95% confidence interval, 1.74-140.23) was associated with ED in men. CONCLUSIONS: Objective measures of disease activity are not associated with SD or ED in patients with IBD. Clinicians should consider concomitant psychological symptoms contributing to the sexual health of patients with IBD.

Identifying Candidate Circulating RNA Markers for Coronary Artery Disease by Deep RNA-Sequencing in Human Plasma.

Advances in RNA sequencing (RNA-Seq) have facilitated transcriptomic analysis of plasma for the discovery of new diagnostic and prognostic markers for disease. We aimed to develop a short-read RNA-Seq protocol to detect mRNAs, long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) in plasma for the discovery of novel markers for coronary artery disease (CAD) and heart failure (HF). Circulating cell-free RNA from 59 patients with stable CAD (half of whom developed HF within 3 years) and 30 controls was sequenced to a median depth of 108 paired reads per sample. We identified fragments from 3986 messenger RNAs (mRNAs), 164 long non-coding RNAs (lncRNAs), 405 putative novel lncRNAs and 227 circular RNAs in plasma. Circulating levels of 160 mRNAs, 10 lncRNAs and 2 putative novel lncRNAs were altered in patients compared with controls (absolute fold change >1.2, p < 0.01 adjusted for multiple comparisons). The most differentially abundant transcripts were enriched in mRNAs encoded by the mitochondrial genome. We did not detect any differences in the plasma RNA profile between patients who developed HF compared with those who did not. In summary, we show that mRNAs, lncRNAs and circular RNAs can be reliably detected in plasma by deep RNA-Seq. Multiple coding and non-coding transcripts were altered in association with CAD, including several mitochondrial mRNAs, which may indicate underlying myocardial ischaemia and oxidative stress. If validated, circulating levels of these transcripts could potentially be used to help identify asymptomatic individuals with established CAD prior to an acute coronary event.

Circulating cardiac biomarkers improve risk stratification for incident cardiovascular disease in community dwelling populations.

BACKGROUND: Plasma cardiac markers may assist in prediction of incident cardiovascular disease. METHODS: The incremental value of cardiac Troponins (T and I) and NT-proBNP added to risk factors in the PREDICT score for incident cardiovascular disease (CVD) in primary care, was assessed in 4102 asymptomatic participants in a randomised controlled trial of Vitamin D (ViDA). Findings were corroborated in 2528 participants in a separate community-based observational registry of CVD-free volunteers (HVOLS). FINDINGS: Hazard ratios for first cardiovascular events adjusted for PREDICT risk factors, comparing fifth to first quintiles of marker plasma concentrations, were 2.57 (95% CI 1.47-4.49); 3.01 (1.66-5.48) and 3.38 (2.04-5.60) for hs-cTnI, hs-cTnT and NT-proBNP respectively. The C statistic for discrimination of the primary endpoint increased from 0.755 to 0.771 (+0.016, p = 0.01). Cardiac marker data correctly reclassified risk upwards in 6.7% of patients and downwards in 3.3%. These findings were corroborated by results from HVOLS. INTERPRETATION: Increments in plasma cardiac biomarkers robustly and reproducibly predicted increased hazard of incident CVD, independent of established risk factors, in two community-dwelling populations. Cardiac markers may augment risk assessment for onset of CVD in primary care. FUNDING: ViDA was funded by the Health Research Council of New Zealand (grant 10/400) and the Accident Compensation Corporation. HVOLS was funded by the Health Research Council of NZ Programme Grants (grants 02/152 and 08/070) and by grants from the Heart Foundation of NZ and the Christchurch Heart Institute Trust. Roche Diagnostics provided in-kind support for NT-proBNP and hs-cTnT assays and Abbott Laboratories for hs-cTnI assays.

Faecal Myeloperoxidase as a Biomarker of Endoscopic Activity in Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Inflammatory bowel disease [IBD], consisting of Crohn's disease [CD] and ulcerative colitis [UC], is a relapsing-remitting illness. Treat-to-target IBD management strategies require monitoring of gastrointestinal inflammation. This study aimed to investigate faecal myeloperoxidase [fMPO], a neutrophil granule enzyme, as a biomarker of IBD activity. METHODS: Prospectively recruited participants with IBD, undergoing ileocolonoscopy for disease assessment, provided biological samples and completed symptom questionnaires prior to endoscopy. fMPO, C-reactive protein [CRP], and faecal calprotectin [fCal] were compared with validated endoscopic indices [simple endoscopic score for CD and UC endoscopic index of severity]. Receiver operating characteristic [ROC] curves assessed the performance of fMPO, CRP, and fCal in predicting endoscopic disease activity. Baseline biomarkers were used to predict a composite endpoint of complicated disease at 12 months [need for escalation of biologic/immunomodulator due to relapse, steroid use, IBD-related hospitalisation, and surgery]. RESULTS: A total of 172 participants were recruited [91 female, 100 with CD]. fMPO was significantly correlated with endoscopic activity in both CD [r = 0.53, p < 0.01] and UC [r = 0.63, p < 0.01], and with fCal in all patients with IBD [r = 0.82, p < 0.01]. fMPO was effective in predicting moderate-to-severely active CD [AUROC 0.86, p < 0.01] and UC [AUROC 0.92, p < 0.01]. Individuals with a baseline fMPO > 26 µg/g were significantly more likely to reach the composite outcome at 12 months (hazard ratio [HR] 3.71, 95% confidence interval [CI] 2.07-6.64, p < 0.01). CONCLUSIONS: Faecal myeloperoxidase is an accurate biomarker of endoscopic activity in IBD and predicted a more complicated IBD course during follow-up.