IOC Olympian Health Cohort: a study protocol for a 15-year, prospective, Olympian health study across Summer and Winter Olympic sports.

Prevention of sports injury and illness and protection of athlete health are key mandates of the IOC. Methodological limitations in Olympic Games surveillance and retired Olympian studies mean there are gaps in the available evidence on Olympian health and the varied challenges occurring at different stages throughout an athlete's career. This (protocol) paper describes the methods for implementation of the IOC Olympian Health Cohort. The study aims to establish a longitudinal cohort of current Olympians and follow them prospectively (around 15 years) throughout their Olympic careers and retirement. The study will use participants who have completed self-report questionnaires. Olympians will be recruited after each Summer and Winter Olympic Games, and all National Olympic Committee (NOC) athletes aged 16 years or older are eligible. The first phase included the Tokyo 2020/2021 and Beijing 2022 Olympians, with the study promoted via IOC platforms, Athlete365 and NOCs. Questionnaires include baseline demographics, sports exposure and history of injuries and illnesses impacting the athlete's ability to continue to train and/or compete for at least 2 weeks. Questions also address retirement from sports, musculoskeletal, mental and general health, and quality of life measures. This protocol describes the methods for the 15-year global IOC Olympian Health Cohort Study, from participant recruitment to the development and distribution of the study questionnaire. This protocol will be updated to report future changes in the study's conduct or questionnaire content. These data will help identify risk factors and inform risk-reduction strategies. The ultimate goal is to protect the health of all athletes during their careers and retirement.

Machine-learning-based integrative -'omics analyses reveal immunologic and metabolic dysregulation in environmental enteric dysfunction.

Environmental enteric dysfunction (EED) is a subclinical enteropathy challenging to diagnose due to an overlap of tissue features with other inflammatory enteropathies. EED subjects (n = 52) from Pakistan, controls (n = 25), and a validation EED cohort (n = 30) from Zambia were used to develop a machine-learning-based image analysis classification model. We extracted histologic feature representations from the Pakistan EED model and correlated them to transcriptomics and clinical biomarkers. In-silico metabolic network modeling was used to characterize alterations in metabolic flux between EED and controls and validated using untargeted lipidomics. Genes encoding beta-ureidopropionase, CYP4F3, and epoxide hydrolase 1 correlated to numerous tissue feature representations. Fatty acid and glycerophospholipid metabolism-related reactions showed altered flux. Increased phosphatidylcholine, lysophosphatidylcholine (LPC), and ether-linked LPCs, and decreased ester-linked LPCs were observed in the duodenal lipidome of Pakistan EED subjects, while plasma levels of glycine-conjugated bile acids were significantly increased. Together, these findings elucidate a multi-omic signature of EED.

"Aberrant" expression of skeletal muscle markers in neuroendocrine carcinomas: a significant diagnostic pitfall.

In this study, we investigate the expression of muscle markers, including the specific skeletal muscle markers myogenin and myoD1, in neuroendocrine carcinomas (NECs). The study included 23 NECs from various sites (14 small cell NECs and 9 large cell NECs). These were stained with desmin, myogenin and myoD1. Positive staining with at least one muscle marker was observed in 14 cases (61%). 8 (35%), 8 (35%) and 11 (48%) of the cases were positive with desmin, myogenin and myoD1 respectively. In most, but not all, cases positive staining was focal generally involving < 10% of tumour cells. Expression of muscle markers is not uncommon in NECs. This represents an important diagnostic pitfall of which pathologists should be aware. In reporting this phenomenon, we speculate on the pathogenesis of this "aberrant" expression of muscle markers.

What did we learn about elite student-athlete mental health systems from the COVID-19 pandemic?

Elite student-athletes (SAs) in higher education (HE) have distinct mental health (MH) risks. The COVID-19 pandemic put pressure on systems and increased elite SA vulnerability to adverse MH outcomes. The aim of this study was to explore the provision and management of MH in elite HE sports settings during the time of COVID-19 pandemic stress. The secondary aim was to identify lessons and opportunities to enhance future mental healthcare systems and services for elite SAs. A qualitative study design was used to investigate the views of three groups (athletic directors, coaches and sport healthcare providers). Ten key leaders were purposively recruited from HE institutions in Canada, the USA and the United Kingdom. They represented various universities from the National College Athletic Association, U SPORTS Canada and British Universities and Colleges Sport. Semistructured interviews were conducted, recorded, transcribed and thematically analysed. Five key themes were identified: (1) The pandemic disruption had salient impacts on motivation and how elite SAs engaged with sport (2) when student sport systems are under pressure, support staff perceive a change in duties and experience their own MH challenges, (3) the pandemic increased awareness about MH care provision and exposed systemic challenges, (4) digital transformation in MH is complex and has additional challenges for SAs and (5) there were some positive outcomes of the pandemic, lessons learnt and a resulting motivation for systems change. Participants highlighted future opportunities for MH provision in elite university sport settings. Four recommendations were generated from the results.

Nationwide survey of Helicobacter pylori seropositivity and gastric atrophy in Zambia.

BACKGROUND: Helicobacter pylori (H. pylori) is a common bacterial infection which predominately drives upper gastrointestinal pathology. We carried out a nationwide serological survey in response to the deficiency of robust African data on H. pylori prevalence, age of acquisition, socio-geographic determinants, and impact on gastric physiology. MATERIALS AND METHODS: This was a cross-sectional study of archival plasma samples collected during the Zambia Population-based HIV impact Assessment (ZAMPHIA) 2016 survey. ZAMPHIA used a two-stage door-to-door stratified cluster sample approach to collect samples from adults and children from age 0 to 59 years (n = 24,266). We randomly retrieved one fifth of these samples from each of Zambia's 10 provinces and used ELISA to test for H. pylori IgG antibodies, pepsinogen 1 and 2 and gastrin-17. A pepsinogen 1:2 ratio of <3 was used to define gastric atrophy. RESULTS: The analysis of 4050 plasma samples (30% <16 years, 53% females) revealed an overall H. pylori seroprevalence of 79%. By the age of 10 years, more than 75% of the children had H. pylori. Urban residence was associated with increased odds (OR 1.8, 95% CI 1.5-2.2, p < 0.001) and HIV infection was associated with reduced odds (OR 0.7, 95% CI 0.5-0.9, p = 0.02) of H. pylori seropositivity. Gastric atrophy was detected in 6% of H. pylori seropositive adults below 45 years of age and 9% in those between 45 and 59 years. CONCLUSIONS: We have confirmed a high prevalence of H. pylori seropositivity in Zambia, predominantly in urban settings. The prevalence of gastric atrophy is broadly consistent with other populations around the globe, but our sample did not include adults over 60 years.

Cerebral perfusion is not impaired in persons with moderate obstructive sleep apnoea when awake.

PURPOSE: It is well established that, together with a multitude of other adverse effects on health, severe obstructive sleep apnoea causes reduced cerebral perfusion and, in turn, reduced cerebral function. Less clear is the impact of moderate obstructive sleep apnoea (OSA). Our aim was to determine if cerebral blood flow is impaired in people diagnosed with moderate OSA. METHODS: Twenty-four patients diagnosed with moderate OSA (15 ≤ apnoea-hypopnea index (AHI) < 30) were recruited (aged 32-72, median 59 years, 10 female). Seven controls (aged 42-73 years, median 62 years, 4 female) with an AHI < 5 were also recruited. The OSA status of all participants was confirmed at baseline by unattended polysomnography and they had an MRI arterial-spin-labelling scan of cerebral perfusion. RESULTS: Neither global perfusion nor voxel-wise perfusion differed significantly between the moderate-OSA and control groups. We also compared the average perfusion across three regional clusters, which had been found in a previous study to have significant perfusion differences with moderate-severe OSA versus control, and found no significant difference in perfusion between the two groups. The perfusions were also very close, with means of 50.2 and 51.8 mL/100 g/min for the moderate-OSAs and controls, respectively, with a negligible effect size (Cohen's d = 0.10). CONCLUSION: We conclude that cerebral perfusion is not impaired in people with moderate OSA and that cerebral flow regulatory mechanisms can cope with the adverse effects which occur in moderate OSA. This is an important factor in clinical decisions for prescription of continuous positive airway pressure therapy (CPAP).

Is Scotland Walking in the Right Direction? A Cross-Sectional Analysis of Trends in Walking by Socioeconomic Status.

BACKGROUND: Walking is a key target behavior for promoting population health. This paper charts the 30-year history of walking policy in Scotland. We assess whether population walking levels among adults in Scotland have changed in recent years and identify the characteristics of those least likely to report any walking. METHODS: We pooled 9 years (2012-2019 and 2021) of data from adult (≥16 y) respondents of the Scottish Health Survey (n = 41,470). The outcomes of interest were the percentage reporting (1) any walking and (2) any walking with an average pace that is of at least moderate intensity. We also investigated the contribution of walking to total nonoccupational moderate to vigorous physical activity. We used linear and logistic regressions to test linear trends over time and to identify inequalities by age, sex, and the Scottish Index of Multiple Deprivation quintile. RESULTS: There was an increase in all measures of walking over the period 2012-2021; for example, the percentage reporting any walking increased by 7 percentage points (81.4%-88.4%). Inequalities still exist by age, sex, and the Scottish Index of Multiple Deprivation but have not grown over time. Inequalities by sex and age are most pronounced in the least affluent Scottish Index of Multiple Deprivation quintiles; less affluent older women are least likely to report any walking. CONCLUSIONS: Scotland appears to be walking in the right direction. Surveillance data support a positive trend after decades of policy and promotion efforts. The policies do not appear to be exacerbating existing inequalities, but narrowing them will require more concentrated efforts.

Malnutrition enteropathy in Zambian and Zimbabwean children with severe acute malnutrition: A multi-arm randomized phase II trial.

Malnutrition underlies almost half of all child deaths globally. Severe Acute Malnutrition (SAM) carries unacceptable mortality, particularly if accompanied by infection or medical complications, including enteropathy. We evaluated four interventions for malnutrition enteropathy in a multi-centre phase II multi-arm trial in Zambia and Zimbabwe and completed in 2021. The purpose of this trial was to identify therapies which could be taken forward into phase III trials. Children of either sex were eligible for inclusion if aged 6-59 months and hospitalised with SAM (using WHO definitions: WLZ <-3, and/or MUAC <11.5 cm, and/or bilateral pedal oedema), with written, informed consent from the primary caregiver. We randomised 125 children hospitalised with complicated SAM to 14 days treatment with (i) bovine colostrum (n = 25), (ii) N-acetyl glucosamine (n = 24), (iii) subcutaneous teduglutide (n = 26), (iv) budesonide (n = 25) or (v) standard care only (n = 25). The primary endpoint was a composite of faecal biomarkers (myeloperoxidase, neopterin, α1-antitrypsin). Laboratory assessments, but not treatments, were blinded. Per-protocol analysis used ANCOVA, adjusted for baseline biomarker value, sex, oedema, HIV status, diarrhoea, weight-for-length Z-score, and study site, with pre-specified significance of P < 0.10. Of 143 children screened, 125 were randomised. Teduglutide reduced the primary endpoint of biomarkers of mucosal damage (effect size -0.89 (90% CI: -1.69,-0.10) P = 0.07), while colostrum (-0.58 (-1.4, 0.23) P = 0.24), N-acetyl glucosamine (-0.20 (-1.01, 0.60) P = 0.67), and budesonide (-0.50 (-1.33, 0.33) P = 0.32) had no significant effect. All interventions proved safe. This work suggests that treatment of enteropathy may be beneficial in children with complicated malnutrition. The trial was registered at ClinicalTrials.gov with the identifier NCT03716115.

Endoscopic diagnosis of gastric and oesophageal cancer in Lusaka, Zambia: a retrospective analysis.

INTRODUCTION: There are uncertainties surrounding the spectrum of upper gastrointestinal (UGI) diseases in sub-Saharan Africa. This is mainly due to the limitations of data collection and recording. We previously reported an audit of UGI endoscopic diagnoses in Zambia spanning from 1977 to 2014. We now have extended this analysis to include subsequent years, in order to provide a more comprehensive picture of how the diagnoses have evolved over 4 decades. METHODS: We combined data collected from the endoscopy unit at the University Teaching Hospital (UTH) in Lusaka during a previous review with that collected from the beginning of 2015 to the end of 2021. Since 2015, an electronic data base of endoscopy reports at the UTH was kept. The electronic data base was composed of drop-down menus that allowed for standardised reporting of findings. Collected data were coded by two experienced endoscopists and analysed. RESULTS: In total, the analysis included 25,849 endoscopic records covering 43 years. The number of endoscopic procedures performed per year increased drastically in 2010. With the exception of the last 2 years, the proportion of normal endoscopies also increased during the time under review. In total, the number of gastric cancer (GC) cases was 658 (3%) while that of oesophageal cancer (OC) was 1168 (5%). The number of GC and OC diagnoses increased significantly over the period under review, (p < 0.001 for both). For OC the increase remained significant when analysed as a percentage of all procedures performed (p < 0.001). Gastric ulcers (GU) were diagnosed in 2095 (8%) cases, duodenal ulcers (DU) in 2276 (9%) cases and 239 (1%) had both ulcer types. DU diagnosis showed a significantly decreasing trend over each decade (p < 0.001) while GU followed an increasing trend (p < 0.001). CONCLUSIONS: UGI endoscopic findings in Lusaka, Zambia, have evolved over the past four decades with a significant increase of OC and GU diagnoses. Reasons for these observations are yet to be established.

Inflammation and cytomegalovirus viremia during pregnancy drive sex-differentiated differences in mortality and immune development in HIV-exposed infants.

Children who are HIV-exposed but uninfected have increased infectious mortality compared to HIV-unexposed children, raising the possibility of immune abnormalities following exposure to maternal viraemia, immune dysfunction, and co-infections during pregnancy. In a secondary analysis of the SHINE trial in rural Zimbabwe we explored biological pathways underlying infant mortality, and maternal factors shaping immune development in HIV-exposed uninfected infants. Maternal inflammation and cytomegalovirus viraemia were independently associated with infant deaths: mortality doubled for each log10 rise in maternal C-reactive protein (adjusted hazard ratio (aHR) 2.09; 95% CI 1.33-3.27), and increased 1.6-fold for each log10 rise in maternal cytomegalovirus viral load (aHR 1.62; 95% CI 1.11-2.36). In girls, mortality was more strongly associated with maternal C-reactive protein than cytomegalovirus; in boys, mortality was more strongly associated with cytomegalovirus than C-reactive protein. At age one month, HIV-exposed uninfected infants had a distinct immune milieu, characterised by raised soluble CD14 and an altered CD8 + T-cell compartment. Alterations in immunophenotype and systemic inflammation were generally greater in boys than girls. Collectively, these findings show how the pregnancy immune environment in women with HIV underlies mortality and immune development in their offspring in a sex-differentiated manner, and highlights potential new intervention strategies to transform outcomes of HIV-exposed children. ClinicalTrials.gov/NCT01824940.

Health Benefits of Different Sports: a Systematic Review and Meta-Analysis of Longitudinal and Intervention Studies Including 2.6 Million Adult Participants.

BACKGROUND: Several reviews have examined the health benefits of participation in specific sports, such as baseball, cricket, cross-country skiing, cycling, downhill skiing, football, golf, judo, rugby, running and swimming. However, new primary studies on the topic have recently been published, and the respective meta-analytic evidence needs to be updated. OBJECTIVES: To systematically review, summarise and appraise evidence on physical health benefits of participation in different recreational sports. METHODS: Searches for journal articles were conducted in PubMed/MEDLINE, Scopus, SpoLit, SPORTDiscus, Sports Medicine & Education Index and Web of Science. We included longitudinal and intervention studies investigating physical health outcomes associated with participation in a given sport among generally healthy adults without disability. RESULTS: A total of 136 papers from 76 studies conducted among 2.6 million participants were included in the review. Our meta-analyses of available evidence found that: (1) cycling reduces the risk of coronary heart disease by 16% (pooled hazard ratio [HR] = 0.84; 95% confidence interval [CI]: 0.80, 0.89), all-cause mortality by 21% (HR = 0.79; 95% CI: 0.73, 0.84), cancer mortality by 10% (HR = 0.90; 95% CI: 0.85, 0.96) and cardiovascular mortality by 20% (HR = 0.80; 95% CI: 0.74, 0.86); (2) football has favourable effects on body composition, blood lipids, fasting blood glucose, blood pressure, cardiovascular function at rest, cardiorespiratory fitness and bone strength (p < 0.050); (3) handball has favourable effects on body composition and cardiorespiratory fitness (p < 0.050); (4) running reduces the risk of all-cause mortality by 23% (HR = 0.77; 95% CI: 0.70, 0.85), cancer mortality by 20% (HR = 0.80; 95% CI: 0.72, 0.89) and cardiovascular mortality by 27% (HR = 0.73; 95% CI: 0.57, 0.94) and improves body composition, cardiovascular function at rest and cardiorespiratory fitness (p < 0.010); and (5) swimming reduces the risk of all-cause mortality by 24% (HR = 0.76; 95% CI: 0.63, 0.92) and improves body composition and blood lipids (p < 0.010). CONCLUSIONS: A range of physical health benefits are associated with participation in recreational cycling, football, handball, running and swimming. More studies are needed to enable meta-analyses of health benefits of participation in other sports. PROSPERO registration number CRD42021234839.

Duodenal quantitative mucosal morphometry in children with environmental enteric dysfunction: a cross-sectional multi-country analysis.

BACKGROUND: Environmental enteric dysfunction (EED), a chronic inflammatory condition of the small intestine, is an important driver of childhood malnutrition globally. Quantifying intestinal morphology in EED allows for exploration of its association with functional and disease outcomes. OBJECTIVE: We sought to define morphometric characteristics of childhood EED and determine whether morphology features were associated with disease pathophysiology. METHODS: Morphometric measurements and histology were assessed on duodenal biopsy slides for this cross-sectional study from children with EED in Bangladesh, Pakistan, and Zambia (n=69), and those with no pathologic abnormality (NPA; n=8) or celiac disease (n=18) in North America. Immunohistochemistry was also conducted on 46, 8, and 18 biopsy slides, respectively. Linear mixed-effects regression models were used to reveal morphometric differences between EED compared to NPA or celiac disease, and identify associations between morphometry and histology or immunohistochemistry amongst children with EED. RESULTS: In duodenal biopsies, median EED villus height (248 µm), crypt depth (299 µm), and villus:crypt (V:C) ratio (0.9) values ranged between those of NPA (396 µm villus height; 246 µm crypt depth; 1.6 V:C ratio) and celiac disease (208 µm villus height; 365 µm crypt depth; 0.5 V:C ratio). Among EED biopsy slides, morphometric assessments were not associated with histologic parameters or immunohistochemical markers, other than pathologist determined subjective semi-quantitative villus architecture. CONCLUSIONS: Morphometric analysis of duodenal biopsy slides across geographies identified morphologic features of EED, specifically short villi, elongated crypts, and a smaller V:C ratio relative to NPA slides; although not as severe as in celiac slides. Morphometry did not explain other EED features, suggesting that EED histopathologic processes may be operating independently of morphology. While acknowledging the challenges with obtaining relevant tissue, these data form the basis for further assessments of the role of morphometry in EED.

A direct analysis method using sheath flow probe electrospray ionisation-mass spectrometry (sfPESI-MS) to detect drug residues from fingerprint forensic gel lifts.

Latent fingerprints at crime scenes are frequently recovered using forensic gel-lifters, which can help to preserve the crime scene and to enhance visualisation of traces such as blood or paint. In addition to providing fingerprint ridge detail, additional chemical information can also be recovered from gel lifts that may prove pertinent to an investigation. However, while DNA and metal ions have been shown to be able to be detected in gel-lifted fingerprints, the determination of other types of chemical information such as the presence of drugs in gel-lifted prints has not been previously shown. This study demonstrates the application of an ambient ionisation method, sheath flow probe electrospray ionisation-mass spectrometry (sfPESI-MS), to the direct analysis of gel-lifted fingerprints. A model drug compound (zolpidem) is successfully detected from gel-lifted prints from three different surface types: glass, metal, and paper. The surface activity-based separation associated with probe electrospray approaches is shown to resolve zolpidem ions from background phthalate species, significantly enhancing the response obtained from the gel-lifter. A depletion series experiment shows that the drug residue can be detected with up to 100% efficiency after eight consecutive contacts; however, detection efficiency drops to 20% after 30 contacts. The developed approach has potential application to analysis of historical gel-lifters to obtain additional chemical information.

The Effect of Hydrostatic Pressure on Coronary Flow and Pressure-Based Indices of Coronary Stenosis Severity.

Background: To assess whether hydrostatic pressure gradients caused by coronary height differences in supine versus prone positioning during invasive physiological stenosis assessment affect resting and hyperaemic pressure-based indices or coronary flow. Methods: Twenty-three coronary stenoses were assessed in twenty-one patients with stable coronary artery disease. All patients had a stenosis of at least 50% visually defined on previous coronary angiography. Pd/Pa, iFR, FFR, and coronary flow velocity (APV) measured using a Doppler were recorded across the same stenosis, with the patient in the prone position, followed by repeat measurements in the standard supine position. Results: When comparing prone to supine measurements in the same stenosis, in the LAD, there was a significant change in mean Pd/Pa of 0.08 ± 0.04 (p = 0.0006), in the iFR of 0.06 ± 0.07 (p = 0.02), and in the FFR of 0.09 ± 0.07 (p = 0.003). In the Cx, there was a change in mean Pd/Pa of 0.05 ± 0.04 (p = 0.009), iFR of 0.07 ± 0.04 (p = 0.01), and FFR of 0.05 ± 0.03 (p = 0.006). In the RCA, there was a change in Pd/Pa of 0.05 ± 0.04 (p = 0.032), iFR of 0.04 ± 0.05 (p = 0.19), and FFR of 0.04+-0.03 (p = 0.004). Resting and hyperaemic coronary flow did not change significantly (resting delta APV = 1.6 cm/s, p = 0.31; hyperaemic delta APV = 0.9 cm/s, p = 0.85). Finally, 36% of iFR measurements and 26% of FFR measurements were re-classified across an ischaemic threshold when prone and supine measurements were compared across the same stenosis. Conclusions: Pd/Pa, iFR, and FFR were affected by hydrostatic pressure variations caused by coronary height differences in prone versus supine positioning. Coronary flow did not change signifying a purely pressure-based phenomenon.

FIVE YEARS OF PARTULA SNAIL PRE-EXPORT HEALTH SCREENING.

Between 2015 and 2019, a health screening was carried out annually on captive-bred Partula snails prior to export for reintroduction as part of an international effort to repopulate areas of French Polynesia, where the snails were extinct or critically endangered. In total, 129 separate tank populations of 12 different species were screened at ZSL London Zoo. Wet mounts and smears stained with modified Ziehl-Neelsen (MZN) of 535 fecal samples were examined, and 45% contained flagellated protozoa, and 35.5% had MZN-positive oocysts, measuring 3-5 µm in diameter. Smaller (2 µm) presumptive spores, MZN-positive bacilli, ciliated protozoa and nematodes were recorded less frequently. Fecal bacterial culture yielded mixed species, with a clear predominance of Myroides species (88.9% of samples). The MZN-positive oocysts (3-5 µm) were present in 6.5% of impression smears from the apices of 432 snails examined postmortem, plus acid-fast bacilli in a few cases, but no 2 µm spores. Mixed bacteria were cultured from coelomic swabs, with Myroides species again the most common (63.5%). Histologic examination was carried out on 292 snails. Autolysis affected almost 90% of those found dead but only 3.4% of euthanized snails. Histology commonly identified microsporidial sporocysts in the digestive gland and midgut epithelium of all but two species. Intracellular, extracytoplasmic Cryptosporidium-like organisms were also common in the midgut but were only observed when snails were fixed in 10% formalin (2017-2019), not ethanol. There were no clear pathologic changes associated with either organism. Pigmented hemocytic nodules were commonly observed, most frequently in the foot process; these were either age related or evidence of prior chronic inflammatory reaction and of low clinical significance. With no evidence of poor health and no significant organisms found, a total of 4,978 individuals representing 12 species were exported for reintroduction.

Chronic total occlusion in non-ST elevation myocardial infarction - A multi-centre observational study.

OBJECTIVES: To evaluate the characteristics and outcomes of patients with a chronic total occlusion (CTO) in a Non-ST Elevation Myocardial Infarction (NSTEMI) cohort. BACKGROUND: There is limited data on the clinical characteristics, revascularisation strategies and outcomes of patients presenting with a NSTEMI and a CTO. METHODS: Retrospective analysis of a six-centre percutaneous coronary intervention (PCI) registry in the UK between January 2015 and December 2020 was performed. Patients with a NSTEMI with and without a CTO were compared for baseline characteristics and outcomes. RESULTS: There were 17,355 NSTEMI patients in total of whom 1813 patients had a CTO (10.4 %). Patients with a CTO were more likely to be older (CTO: 67.8 (±11.5) years vs. no CTO: 67.2 (±12) years, p = 0.04), male (CTO: 81.1 % vs.71.9 %, p < 0.0001) with a greater prevalence of cardiovascular risk factors. All-cause mortality at 30 days: HR 2.63, 95 % CI 1.42-4.84, p = 0.002 and at 1 year: HR: 1.87, 95 % CI 1.25-2.81, p = 0.003 was higher in the CTO cohort. CTO patients who underwent revascularisation were younger (Revascularisation 66.4 [±11.7] years vs. no revascularisation 68.4 [±11.4] years, p = 0.001). Patients with failed CTO revascularisation had lower survival (HR 0.21, 95 % CI 0.10-0.42, p < 0.0001). The mean time to revascularisation was 13.4 days. There was variation in attempt at CTO revascularisation between the 6 centres for (16 % to 100 %) with success rates ranging from 65 to 100 %. CONCLUSIONS: In conclusion, the presence of a CTO in NSTEMI patients undergoing PCI was associated with worse in-hospital and long-term outcomes.

Transcutaneous fluorescence spectroscopy: development and characterization of a compact, portable, and fiber-optic sensor.

Significance: The integrity of the intestinal barrier is gaining recognition as a significant contributor to various pathophysiological conditions, including inflammatory bowel disease, celiac disease, environmental enteric dysfunction (EED), and malnutrition. EED, for example, manifests as complex structural and functional changes in the small intestine leading to increased intestinal permeability, inflammation, and reduced absorption of nutrients. Despite the importance of gut function, current techniques to assess intestinal permeability (such as endoscopic biopsies or dual sugar assays) are either highly invasive, unreliable, and/or difficult to perform in certain patient populations (e.g., infants). Aim: We present a portable, optical sensor based on transcutaneous fluorescence spectroscopy to assess gut function (in particular, intestinal permeability) in a fast and noninvasive manner. Approach: Participants receive an oral dose of a fluorescent contrast agent, and a wearable fiber-optic probe detects the permeation of the contrast agent from the gut into the blood stream by measuring the fluorescence intensity noninvasively at the fingertip. We characterized the performance of our compact optical sensor by comparing it against an existing benchtop spectroscopic system. In addition, we report results from a human study in healthy volunteers investigating the impact of skin tone and contrast agent dose on transcutaneous fluorescence signals. Results: The first study with eight healthy participants showed good correlation between our compact sensor and the existing benchtop spectroscopic system [correlation coefficient (r)>0.919, p<0.001]. Further experiments in 14 healthy participants revealed an approximately linear relationship between the ingested contrast agent dose and the collected signal intensity. Finally, a parallel study on the impact of different skin tones showed no significant differences in signal levels between participants with different skin tones (p>0.05). Conclusions: In this paper, we demonstrate the potential of our compact transcutaneous fluorescence sensor for noninvasive monitoring of intestinal health.

Enteroblastic cholangiocarcinoma: An uncommon, underrecognized subtype of bile duct cancer.

Enteroblastic carcinoma is clinically characterized by an elevated serum level of alpha-fetoprotein (AFP) and is histologically characterized by cancer cells with a clear cytoplasm and 'blastic' coarse chromatin. It sometimes has an element of hepatoid carcinoma; therefore, these two neoplasms are often regarded as sister entities. Although hepatoid carcinoma in the biliary tree has been reported, enteroblastic cholangiocarcinoma is extremely uncommon. In the present study, four cases of enteroblastic cholangiocarcinoma were examined. Tumors were located inside the liver (n = 2) or common bile duct (n = 2). The two intrahepatic cases had a history of primary sclerosing cholangitis, and serum AFP levels were elevated in both. One unresectable case was diagnosed by needle liver biopsy, while the remaining three underwent surgical resection. Histologically, all cases showed similar microscopic features. Cuboidal or polygonal cancer cells with the characteristic clear cytoplasm and subnuclear vacuoles were arranged in a papillary, micropapillary, tubular, or solid architecture. One case had an element of pancreatobiliary-type adenocarcinoma, while a hepatoid carcinoma element was not observed in any cases. All cases were positive for AFP, glypican 3, and SALL4, with SALL4 being the most widely expressed. Heppar-1 and arginase-1 were negative, except for one case, which was positive for Heppar-1. In conclusion, enteroblastic cholangiocarcinoma is an uncommon subtype of biliary tract malignancy. These cases may have been categorized as 'clear cell' cholangiocarcinoma. Although enteroblastic cholangiocarcinoma seems to occur more commonly in extrahepatic regions, including the gallbladder, it may also develop in the liver, particularly in patients with primary sclerosing cholangitis.

Inflammation and epithelial repair predict mortality, hospital readmission, and growth recovery in complicated severe acute malnutrition.

Severe acute malnutrition (SAM) is the most high-risk form of undernutrition, particularly when children require hospitalization for complications. Complicated SAM is a multisystem disease with high inpatient and postdischarge mortality, especially in children with comorbidities such as HIV; however, the underlying pathogenesis of complicated SAM is poorly understood. Targeted multiplex biomarker analysis in children hospitalized with SAM (n = 264) was conducted on plasma samples, and inflammatory markers were assessed on stool samples taken at recruitment, discharge, and 12 to 24 and 48 weeks after discharge from three hospitals in Zimbabwe and Zambia. Compared with adequately nourished controls (n = 173), we found that at baseline, complicated SAM was characterized by systemic, endothelial, and intestinal inflammation, which was exacerbated by HIV infection. This persisted over 48 weeks despite nutritional recovery and was associated with children's outcomes. Baseline plasma concentrations of vascular endothelial growth factor, glucagon-like peptide-2, and intestinal fatty acid-binding protein were independently associated with lower mortality or hospital readmission over the following 48 weeks. Following principal components analysis of baseline biomarkers, higher scores of a component representing growth factors was associated with greater weight-for-height z score recovery and lower mortality or hospital readmission over the 48 weeks. Conversely, components representing higher gut and systemic inflammation were associated with higher mortality or hospital readmission. These findings highlight the interplay between inflammation, which damages tissues, and growth factors, which mediate endothelial and epithelial regeneration, and support further studies investigating interventions to reduce inflammation and promote epithelial repair as an approach to reducing mortality and improving nutritional recovery.