The gut microbiome associates with phenotypic manifestations of post-acute COVID-19 syndrome.

The mechanisms underlying the many phenotypic manifestations of post-acute COVID-19 syndrome (PACS) are poorly understood. Herein, we characterized the gut microbiome in heterogeneous cohorts of subjects with PACS and developed a multi-label machine learning model for using the microbiome to predict specific symptoms. Our processed data covered 585 bacterial species and 500 microbial pathways, explaining 12.7% of the inter-individual variability in PACS. Three gut-microbiome-based enterotypes were identified in subjects with PACS and associated with different phenotypic manifestations. The trained model showed an accuracy of 0.89 in predicting individual symptoms of PACS in the test set and maintained a sensitivity of 86% and a specificity of 82% in predicting upcoming symptoms in an independent longitudinal cohort of subjects before they developed PACS. This study demonstrates that the gut microbiome is associated with phenotypic manifestations of PACS, which has potential clinical utility for the prediction and diagnosis of PACS.

A synbiotic preparation (SIM01) for post-acute COVID-19 syndrome in Hong Kong (RECOVERY): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Post-acute COVID-19 syndrome (PACS) affects over 65 million individuals worldwide but treatment options are scarce. We aimed to assess a synbiotic preparation (SIM01) for the alleviation of PACS symptoms. METHODS: In this randomised, double-blind, placebo-controlled trial at a tertiary referral centre in Hong Kong, patients with PACS according to the US Centers for Disease Control and Prevention criteria were randomly assigned (1:1) by random permuted blocks to receive SIM01 (10 billion colony-forming units in sachets twice daily) or placebo orally for 6 months. Inclusion criterion was the presence of at least one of 14 PACS symptoms for 4 weeks or more after confirmed SARS-CoV-2 infection, including fatigue, memory loss, difficulty in concentration, insomnia, mood disturbance, hair loss, shortness of breath, coughing, inability to exercise, chest pain, muscle pain, joint pain, gastrointestinal upset, or general unwellness. Individuals were excluded if they were immunocompromised, were pregnant or breastfeeding, were unable to receive oral fluids, or if they had received gastrointestinal surgery in the 30 days before randomisation. Participants, care providers, and investigators were masked to group assignment. The primary outcome was alleviation of PACS symptoms by 6 months, assessed by an interviewer-administered 14-item questionnaire in the intention-to-treat population. Forward stepwise multivariable logistical regression was performed to identify predictors of symptom alleviation. The trial is registered with ClinicalTrials.gov, NCT04950803. FINDINGS: Between June 25, 2021, and Aug 12, 2022, 463 patients were randomly assigned to receive SIM01 (n=232) or placebo (n=231). At 6 months, significantly higher proportions of the SIM01 group had alleviation of fatigue (OR 2·273, 95% CI 1·520-3·397, p=0·0001), memory loss (1·967, 1·271-3·044, p=0·0024), difficulty in concentration (2·644, 1·687-4·143, p<0·0001), gastrointestinal upset (1·995, 1·304-3·051, p=0·0014), and general unwellness (2·360, 1·428-3·900, p=0·0008) compared with the placebo group. Adverse event rates were similar between groups during treatment (SIM01 22 [10%] of 232 vs placebo 25 [11%] of 231; p=0·63). Treatment with SIM01, infection with omicron variants, vaccination before COVID-19, and mild acute COVID-19, were predictors of symptom alleviation (p<0·0036). INTERPRETATION: Treatment with SIM01 alleviates multiple symptoms of PACS. Our findings have implications on the management of PACS through gut microbiome modulation. Further studies are warranted to explore the beneficial effects of SIM01 in other chronic or post-infection conditions. FUNDING: Health and Medical Research Fund of Hong Kong, Hui Hoy and Chow Sin Lan Charity Fund, and InnoHK of the HKSAR Government. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Rise in intraocular pressure with elevator travel in post-vitrectomy patients.

To evaluate the impact of elevator travel on intraocular pressure after vitreoretinal surgery with gas tamponade. Patients undergoing pars plana vitreoretinal surgery with and without gas insertion were recruited on post-operative day 1. All intraocular pressures were measured three times by Tono-Pen AVIA (Reichert, USA) on the fourth floor and, after rapid ascent in an elevator, on the 12th floor of the hospital. All patients were observed and asked for any symptoms of pain or nausea for at least 15 min. In this study, 54 patients were recruited. Twenty-seven patients underwent vitreoretinal procedures with gas insertion, while 27 patients without gas insertion acted as controls. The mean age of patients was 60.9 years. The mean changes in intraocular pressure of the patients with gas insertion (+ 1.39 mmHg) were greater than those without gas insertion (- 0.43 mmHg) and statistically significantly different (95% CI 1.17-2.48, P < 0.0001). Patients undergoing vitreoretinal surgery with gas insertion had statistically significant intraocular pressure rise even with 8-floor ascent in the immediate post-operative period. Further studies are needed to evaluate the change in intraocular pressure with a larger range of altitudes and different gases.

Clinical Applications of Mixed Reality and 3D Printing in Congenital Heart Disease.

Understanding the anatomical features and generation of realistic three-dimensional (3D) visualization of congenital heart disease (CHD) is always challenging due to the complexity and wide spectrum of CHD. Emerging technologies, including 3D printing and mixed reality (MR), have the potential to overcome these limitations based on 2D and 3D reconstructions of the standard DICOM (Digital Imaging and Communications in Medicine) images. However, very little research has been conducted with regard to the clinical value of these two novel technologies in CHD. This study aims to investigate the usefulness and clinical value of MR and 3D printing in assisting diagnosis, medical education, pre-operative planning, and intraoperative guidance of CHD surgeries through evaluations from a group of cardiac specialists and physicians. Two cardiac computed tomography angiography scans that demonstrate CHD of different complexities (atrial septal defect and double outlet right ventricle) were selected and converted into 3D-printed heart models (3DPHM) and MR models. Thirty-four cardiac specialists and physicians were recruited. The results showed that the MR models were ranked as the best modality amongst the three, and were significantly better than DICOM images in demonstrating complex CHD lesions (mean difference (MD) = 0.76, p = 0.01), in enhancing depth perception (MD = 1.09, p = 0.00), in portraying spatial relationship between cardiac structures (MD = 1.15, p = 0.00), as a learning tool of the pathology (MD = 0.91, p = 0.00), and in facilitating pre-operative planning (MD = 0.87, p = 0.02). The 3DPHM were ranked as the best modality and significantly better than DICOM images in facilitating communication with patients (MD = 0.99, p = 0.00). In conclusion, both MR models and 3DPHM have their own strengths in different aspects, and they are superior to standard DICOM images in the visualization and management of CHD.

The role of 3D printed heart models in immediate and long-term knowledge acquisition in medical education.

BACKGROUND: The long-term effect of three-dimensional printed heart model (3DPHM) on knowledge acquisition of congenital heart disease (CHD) remains unknown. This prospective cohort study aims to investigate the role of 3DPHM in improving immediate knowledge gain and long-term knowledge retention on CHD among the medical students. METHODS: Fifty-three second and third year medical students were assigned into two groups to compare their immediate knowledge acquisition and knowledge retention after an education session on anatomy and pathophysiology of CHD. During the 1.5 hour-long education session, both the control (n = 25) and study groups (n = 28) had access to identical teaching materials: digital 3D heart models, 2D diagrams, and medical images, except for 3DPHM which were only used in the study group. The immediate knowledge gain was assessed via an online quiz, whereas the long-term knowledge retention was assessed using another quiz in 6-weeks' time post-intervention. A survey was also conducted to evaluate the participants' learning experience. RESULTS: There is no significant difference in the immediate knowledge acquisition and long-term knowledge retention between the groups (U = 272, p = 0.16 and r = -0.143, p = 0.15 respectively). Majority of the students (96% in control group and 85% in 3DPHM group) responded that the 3DPHM would have/had improved their learning experience. Despite that, there is no significant difference in the self-perceived knowledge improvement between the groups. CONCLUSIONS: This study concludes that the 3DPHM do not significantly improve both immediate knowledge acquisition and knowledge retention among the medical students. However, further research with larger sample size, as well as categorizing the type of questions in the quiz, is needed to better assess the role of 3DPHM in different educational components.

Natural language word embeddings as a glimpse into healthcare language and associated mortality surrounding end of life.

OBJECTIVES: To clarify real-world linguistic nuances around dying in hospital as well as inaccuracy in individual-level prognostication to support advance care planning and personalised discussions on limitation of life sustaining treatment (LST). DESIGN: Retrospective cross-sectional study of real-world clinical data. SETTING: Secondary care, urban and suburban teaching hospitals. PARTICIPANTS: All inpatients in 12-month period from 1 October 2018 to 30 September 2019. METHODS: Using unsupervised natural language processing, word embedding in latent space was used to generate phrase clusters with most similar semantic embeddings to 'Ceiling of Treatment' and their prognostication value. RESULTS: Word embeddings with most similarity to 'Ceiling of Treatment' clustered around phrases describing end-of-life care, ceiling of care and LST discussions. The phrases have differing prognostic profile with the highest 7-day mortality in the phrases most explicitly referring to end of life-'Withdrawal of care' (56.7%), 'terminal care/end of life care' (57.5%) and 'un-survivable' (57.6%). CONCLUSION: Vocabulary used at end-of-life discussions are diverse and has a range of associations to 7-day mortality. This highlights the importance of correct application of terminology during LST and end-of-life discussions.

Clinical Value of Virtual Reality versus 3D Printing in Congenital Heart Disease.

Both three-dimensional (3D) printing and virtual reality (VR) are reported as being superior to the current visualization techniques in conveying more comprehensive visualization of congenital heart disease (CHD). However, little is known in terms of their clinical value in diagnostic assessment, medical education, and preoperative planning of CHD. This cross-sectional study aims to address these by involving 35 medical practitioners to subjectively evaluate VR visualization of four selected CHD cases in comparison with the corresponding 3D printed heart models (3DPHM). Six questionnaires were excluded due to incomplete sections, hence a total of 29 records were included for the analysis. The results showed both VR and 3D printed heart models were comparable in terms of the degree of realism. VR was perceived as more useful in medical education and preoperative planning compared to 3D printed heart models, although there was no significant difference in the ratings (p = 0.54 and 0.35, respectively). Twenty-one participants (72%) indicated both the VR and 3DPHM provided additional benefits compared to the conventional medical imaging visualizations. This study concludes the similar clinical value of both VR and 3DPHM in CHD, although further research is needed to involve more cardiac specialists for their views on the usefulness of these tools.

Dimensional Accuracy and Clinical Value of 3D Printed Models in Congenital Heart Disease: A Systematic Review and Meta-Analysis.

The aim of this paper is to summarize and evaluate results from existing studies on accuracy and clinical value of three-dimensional printed heart models (3DPHM) for determining whether 3D printing can significantly improve on how the congenital heart disease (CHD) is managed in current clinical practice. Proquest, Google Scholar, Scopus, PubMed, and Medline were searched for relevant studies until April 2019. Two independent reviewers performed manual data extraction and assessed the risk of bias of the studies using the tools published on National Institutes of Health (NIH) website. The following data were extracted from the studies: author, year of publication, study design, imaging modality, segmentation software, utility of 3DPHM, CHD types, and dimensional accuracy. R software was used for the meta-analysis. Twenty-four articles met the inclusion criteria and were included in the systematic review. However, only 7 studies met the statistical requirements and were eligible for meta-analysis. Cochran's Q test demonstrated significant variation among the studies for both of the meta-analyses of accuracy of 3DPHM and the utility of 3DPHM in medical education. Analysis of all included studies reported the mean deviation between the 3DPHM and the medical images is not significant, implying that 3DPHM are highly accurate. As for the utility of the 3DPHM, it is reported in all relevant studies that the 3DPHM improve the learning experience and satisfaction among the users, and play a critical role in facilitating surgical planning of complex CHD cases. 3DPHM have the potential to enhance communication in medical practice, however their clinical value remains debatable. More studies are required to yield a more meaningful meta-analysis.

Personalized Three-Dimensional Printed Models in Congenital Heart Disease.

Patient-specific three-dimensional (3D) printed models have been increasingly used in cardiology and cardiac surgery, in particular, showing great value in the domain of congenital heart disease (CHD). CHD is characterized by complex cardiac anomalies with disease variations between individuals; thus, it is difficult to obtain comprehensive spatial conceptualization of the cardiac structures based on the current imaging visualizations. 3D printed models derived from patient's cardiac imaging data overcome this limitation by creating personalized 3D heart models, which not only improve spatial visualization, but also assist preoperative planning and simulation of cardiac procedures, serve as a useful tool in medical education and training, and improve doctor-patient communication. This review article provides an overall view of the clinical applications and usefulness of 3D printed models in CHD. Current limitations and future research directions of 3D printed heart models are highlighted.

Quantitative and qualitative comparison of low- and high-cost 3D-printed heart models.

Current visualization techniques of complex congenital heart disease (CHD) are unable to provide comprehensive visualization of the anomalous cardiac anatomy as the medical datasets can essentially only be viewed from a flat, two-dimensional (2D) screen. Three-dimensional (3D) printing has therefore been used to replicate patient-specific hearts in 3D views based on medical imaging datasets. This technique has been shown to have a positive impact on the preoperative planning of corrective surgery, patient-doctor communication, and the learning experience of medical students. However, 3D printing is often costly, and this impedes the routine application of this technology in clinical practice. This technical note aims to investigate whether reducing 3D printing costs can have any impact on the clinical value of the 3D-printed heart models. Low-cost and a high-cost 3D-printed models based on a selected case of CHD were generated with materials of differing cost. Quantitative assessment of dimensional accuracy of the cardiac anatomy and pathology was compared between the 3D-printed models and the original cardiac computed tomography (CT) images with excellent correlation (r=0.99). Qualitative evaluation of model usefulness showed no difference between the two models in medical applications.

Clinical value of patient-specific three-dimensional printing of congenital heart disease: Quantitative and qualitative assessments.

OBJECTIVE: Current diagnostic assessment tools remain suboptimal in demonstrating complex morphology of congenital heart disease (CHD). This limitation has posed several challenges in preoperative planning, communication in medical practice, and medical education. This study aims to investigate the dimensional accuracy and the clinical value of 3D printed model of CHD in the above three areas. METHODS: Using cardiac computed tomography angiography (CCTA) data, a patient-specific 3D model of a 20-month-old boy with double outlet right ventricle was printed in Tango Plus material. Pearson correlation coefficient was used to evaluate correlation of the quantitative measurements taken at analogous anatomical locations between the CCTA images pre- and post-3D printing. Qualitative analysis was conducted by distributing surveys to six health professionals (two radiologists, two cardiologists and two cardiac surgeons) and three medical academics to assess the clinical value of the 3D printed model in these three areas. RESULTS: Excellent correlation (r = 0.99) was noted in the measurements between CCTA and 3D printed model, with a mean difference of 0.23 mm. Four out of six health professionals found the model to be useful in facilitating preoperative planning, while all of them thought that the model would be invaluable in enhancing patient-doctor communication. All three medical academics found the model to be helpful in teaching, and thought that the students will be able to learn the pathology quicker with better understanding. CONCLUSION: The complex cardiac anatomy can be accurately replicated in flexible material using 3D printing technology. 3D printed heart models could serve as an excellent tool in facilitating preoperative planning, communication in medical practice, and medical education, although further studies with inclusion of more clinical cases are needed.

Three-dimensional printing in congenital heart disease: A systematic review.

Three-dimensional (3D) printing has shown great promise in medicine with increasing reports in congenital heart disease (CHD). This systematic review aims to analyse the main clinical applications and accuracy of 3D printing in CHD, as well as to provide an overview of the software tools, time and costs associated with the generation of 3D printed heart models. A search of different databases was conducted to identify studies investigating the application of 3D printing in CHD. Studies based on patient's medical imaging datasets were included for analysis, while reports on in vitro phantom or review articles were excluded from the analysis. A total of 28 studies met selection criteria for inclusion in the review. More than half of the studies were based on isolated case reports with inclusion of 1-12 cases (61%), while 10 studies (36%) focused on the survey of opinion on the usefulness of 3D printing by healthcare professionals, patients, parents of patients and medical students, and the remaining one involved a multicentre study about the clinical value of 3D printed models in surgical planning of CHD. The analysis shows that patient-specific 3D printed models accurately replicate complex cardiac anatomy, improve understanding and knowledge about congenital heart diseases and demonstrate value in preoperative planning and simulation of cardiac or interventional procedures, assist surgical decision-making and intra-operative orientation, and improve patient-doctor communication and medical education. The cost of 3D printing ranges from USD 55 to USD 810. This systematic review shows the usefulness of 3D printed models in congenital heart disease with applications ranging from accurate replication of complex cardiac anatomy and pathology to medical education, preoperative planning and simulation. The additional cost and time required to manufacture the 3D printed models represent the limitations which need to be addressed in future studies.

Microcalcifications in stone-obstructed human submandibular gland are associated with apoptosis and cell proliferation.

OBJECTIVE: Human submandibular gland (SMG) stones are associated with inflammation, fibrosis and microcalcifications in the surrounding tissues. However, there is little information about the accompanying cell injury-repair process, apoptosis, and cell proliferation. The purpose of this study was to investigate such an association and its clinical significance. DESIGN OF STUDY: Mid-gland paraffin sections of human SMGs ("stone glands") and normal SMGs ("non-stone glands") were subjected to stains for general histology (hematoxylin and eosin), fibrosis (Masson's trichrome), and calcification (alizarin red) and to immunohistochemistry for proliferative activity (Ki-67), and apoptosis (Caspase-3). Tissues were assessed for areas of inflammation, calcium deposition, and fibrosis, and for cycling and apoptotic cells. RESULTS: Acini were atrophic and proportionately fewer in lobules with fibrosis in stone glands. Additionally, stone glands had intraluminal calcifications (microliths) in scattered excretory and striated ducts and blood vessel walls. Areas of inflammation and fibrosis were small and uncommon, and calcifications were not seen in non-stone glands. Proliferating and apoptotic cells were common in the main duct of stone glands where ciliated and mucous cell hyperplasia and stratified squamous metaplasia had occurred, uncommon in the main duct of non-stone glands, and uncommon in all other parenchymal elements of both stone and non-stone glands. CONCLUSION: Stone obstruction in the main excretory ducts of SMG resulted in progressive depletion of acini from proximal to distal lobules via calcification, inflammation, fibrosis, and parenchymal cell atrophy, apoptosis and proliferation. Interlobular duct microliths contributed to this depletion by further provoking intralobular inflammation, fibrosis, and acinar atrophy.

Avoiding the Hughes flap in lower eyelid reconstruction.

PURPOSE OF REVIEW: To review current surgical practices of lower eyelid reconstruction with a focus on recent studies. RECENT FINDINGS: Combination techniques and new flap techniques offer efficacy comparable with existing reconstructive approaches, with the advantage of less local trauma. Inappropriate handling of posterior lamellar grafts, such as kerfing, may predispose to graft failures. Modified Hughes procedure is a favorable choice for large lower eyelid reconstruction; however, it requires temporary eye closure. Other surgical options have been developed to achieve a 1-stage procedure without the need of eye closure. These include the Smith-modified Kuhnt-Szymanowski procedure and the use of flaps. For posterior lamellar grafts, both nasal septal and ear cartilage donor tissue produce esthetically and functionally satisfactory outcomes and comparable efficacy. However, the ear cartilage carries a lower risk of donor site complications. SUMMARY: Lower eyelid reconstruction remains a challenge, especially for large or near total defects. Recent studies have explored modifications and alternatives to the conventional Hughes flap. New surgical procedures give surgeons more options. Taking into account the growing spectrum of reconstructive techniques, an individualized approach may facilitate better functional and esthetic outcomes.

Photo-assisted fenton oxidation of refractory organics in UASB-pretreated leachate.

Nearly 91% of organic pollutants in Hong Kong leachate could be effectively removed by the UASB (upflow anaerobic sludge blanket) process followed by the fenton coagulation. The COD (chemical oxygen demand) of leachate was lowered from an average of 5620 mg/L to 1910 mg/L after the UASB treatment at 37 degrees C, and was further lowered to 513 mg/L after fenton coagulation. The remaining refractory residues could be further removed by photochemical oxidation with the addition of H2O2. The BOD/COD ratio was greatly increased from 0.062 to 0.142, indicating the biodegradability of organic residues was improved. The photochemical oxidation for the fenton-coagulation supernatant was most effective at pH 3-4, with the addition of 800 mg/L of H2O2, and UV radiation time of 30 minutes. The final effluent contained only 148 mg/L of COD, 21 mg/L of BOD (biochemical oxygen demand) and 56 mg/L of TOC (total organic carbon).