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The curia, an international job market and melting pot of ideas, was indisputably a driving force in the renewed appreciation for the Roman heritage. [...]I decided to approach my research as the reconstruction of a network of individuals and families with antiquarian interests. During the final weeks of my Fellowship, I sought to complement this material evidence with a study of the literary descriptions of Rome produced in Cencio's circle.
Balsdon Fellowship: Roman relics and Renaissance collectors 1350C1550
Introduction: To demonstrate public interest in reconstructive urology during the COVID-19 pandemic by using Google Trends (GT). Methods: The study was conducted between August 1 and August 11, 2021. A total of 18 terms related to reconstructive urology were determined. Public interest in all terms were evaluated with the GT application using the filters worldwide, all categories, and web search. To determine public interest in reconstructive urology during the COVID-19 pandemic, three 12-week periods following the declaration of COVID-19 (March 11 to June 4, 2020, June 5 to August 29, 2020, and August 30 to November 23, 2020) were compared with the same periods in the past four years (2016-2019). Results: Comparisons of March 11 to June 4, 2020, and the same days in the previous four years revealed that total public attention to reconstructive urology significantly declined (?16.2%, p=0.035). In the comparison of the second 12-week duration (June 5 to August 29, 2020, vsJune 5 to August 29, 2016-2019), only the bladder augmentation term had significantly lower search frequency during COVID-19 (?46.3%, p=0.043), but buried penis (50.3%, p=0.001), urinary incontinence (15.3%, p=0.001), and stress urinary incontinence (21.7%, p=0.001) keywords had significantly higher inquiries. The comparison of the third 12-week period searches for only urinary incontinence significantly increased (p=0.001). Conclusion: Present study showed that public interest in reconstructive urology significantly reduced in the first 12 weeks after COVID-19 was declared a pandemic. However, public attention to reconstructive urology reached similar levels after 12 weeks from the beginning of COVID-19. Additionally, the term urinary incontinence was searched statistically more frequently during the COVID-19.
The Assessment of Reconstructive Urology-Associated Google Search Trends During COVID-19
BACKGROUND: COVID-19, the disease caused by the highly infectious and transmissible coronavirus SARS-CoV-2, has quickly become a morbid global pandemic. Although the impact of SARS-CoV-2 infection in children is less clinically apparent, collecting high-quality biospecimens from infants, children, and adolescents in a standardized manner during the COVID-19 pandemic is essential to establish a biologic understanding of the disease in the pediatric population. This biorepository enables pediatric centers world-wide to collect samples uniformly to drive forward our understanding of COVID-19 by addressing specific pediatric and neonatal COVID-19-related questions. METHODS: A COVID-19 biospecimen collection study was implemented with strategic enrollment guidelines to include patients seen in urgent care clinics and hospital settings, neonates born to SARS-CoV-2 infected mothers, and asymptomatic children. The methodology described here, details the importance of establishing collaborations between the clinical and research teams to harmonize protocols for patient recruitment and sample collection, processing and storage. It also details modifications required for biobanking during a surge of the COVID-19 pandemic. RESULTS: Considerations and challenges facing enrollment of neonatal and pediatric cohorts are described. A roadmap is laid out for successful collection, processing, storage and database management of multiple pediatric samples such as blood, nasopharyngeal and oropharyngeal swabs, sputum, saliva, tracheal aspirates, stool, and urine. Using this methodology, we enrolled 327 participants, who provided a total of 972 biospecimens. CONCLUSIONS: Pediatric biospecimens will be key in answering questions relating to viral transmission by children, differences between pediatric and adult viral susceptibility and immune responses, the impact of maternal SARS-CoV-2 infection on fetal development, and factors driving the Multisystem Inflammatory Syndrome in Children. The specimens in this biorepository will allow necessary comparative studies between children and adults, help determine the accuracy of current pediatric viral testing techniques, in addition to, understanding neonatal exposure to SARS-CoV-2 infection and disease abnormalities. The successful establishment of a pediatric biorepository is critical to provide insight into disease pathogenesis, and subsequently, develop future treatment and vaccination strategies.
Establishment of a pediatric COVID-19 biorepository: unique considerations and opportunities for studying the impact of the COVID-19 pandemic on children
During 2020, a total of 64 wild boar carcasses were tested for Enterobacteriaceae count (EBC), Salmonella and Yersinia enterocolitica in the abdominal region (i) within 5 h after hunting in the game collection point and (ii) before dressing and processing in the game-handling establishment (GHE) (49 carcassesaverage time interval between (i) and (ii): 4.3 days). Because of COVID-19 restrictions, 15 carcasses were transported to a near slaughterhouse (average time interval between (i) and (ii): 2.3 days). Mesenteric lymph nodes (MLNs) were collected and tested for Salmonella and Y. enterocolitica. Results are shown in relation to sampling A (49 carcassesGHE) and sampling B (15 carcassesslaughterhouse). Sampling A: EBC median values were (i) 2.51 log(10) CFU/cm(2) and (ii) 2.79 log(10) CFU/cm(2). EBC increase between (i) and (ii) was statistically significant (p = 0.001). Salmonella prevalence on carcasses varied from (i) 2.0 to (ii) 6.1%. Sampling B: EBC median values were (i) 3.1 log(10) CFU/cm(2) and (ii) 3.32 log(10) CFU/cm(2). EBC increase between (i) and (ii) was not statistically significant (p = 0.191). Salmonella prevalence on carcasses varied from (i) 6.7 to (ii) 0.0%. The prevalence (sampling A + B) of lymphatic Salmonella carriers was 7.8% (5/64). From carcasses and/or MNLs, the serovars Enteritidis, Typhimurium, Agama, Zaiman and Diarizonae O:50 (z) were detected. Y. enterocolitica was never isolated. Long chilling periods prior to wild game processing should be avoided, and carcasses should be tested at GHE rather than after shooting to proper reflect the microbial load of wild boar meat entering the food chain.
Enterobacteriaceae and Salmonella contamination of wild boar (Sus scrofa) carcasses: comparison between different sampling strategies
This study investigates the impact of aerosol liquid water content (ALWC) and related factors, i.e., relative humidity (RH), aerosol mass concentration (PM2.5), and aerosol hygroscopicity, on aerosol optical properties, based on field measurements made in the Pearl River Delta (PRD) region of China at the surface (1 November 2019 to 21 January 2020) and in the upper boundary layer (the 532-m Guangzhou tower from 1 February to 21 March 2020). In general, temporal variations in the ambient aerosol backscattering coefficient (p) and ALWC followed each other. However, the surface p and 532-m p had generally opposite diurnal variation patterns, caused by dramatic differences in PM2.5 and ambient RH between the surface and the upper boundary layer. The ambient 532-m RH was systematically higher than the surface RH, with the latter having a much pronounced diurnal cycle than the former. The surface PM2.5 concentration was systematically higher than the PM2.5 concentration at 532 m, and their diurnal cycle patterns were overall opposite. These dramatic differences reveal that the atmospheric variables, i.e., ambient RH and the PM2.5 concentration in the upper boundary layer, cannot be directly represented by the same variables at the surface. Vertical variability should be considered. Clear differences in the sensitivities of aerosol light scattering to ambient RH, PM2.5, and aerosol hygroscopicity between the two levels were found and examined. Aerosol chemical composition played a minor role in causing the differences between the two levels. In particular, p was more sensitive to PM2.5 at the surface level but more to the ambient RH in the upper boundary layer. The larger contribution of aerosol loading to the variability in p at the surface implies that local emission controls can decrease p and further improve atmospheric visibility effectively at the surface during winter in the PRD region.
The different sensitivities of aerosol optical properties to particle concentration, humidity, and hygroscopicity between the surface level and the upper boundary layer in Guangzhou, China.
Introduction: In January 2020, World Health Organization declared the outbreak of novel coronavirus a pandemic (global health emergency). The aim of this study was to assess the knowledge about novel coronavirus and its determinant factors among health science students at Arbaminch Health Sciences College, Southwest Ethiopia.Method A cross-sectional study design was employed to assess the level knowledge about novel coronavirus among 304 graduating class students in Arbaminch Health Science College. The study participants were selected using a simple random sampling technique. The data collection tool consisted of 33 items (10 items about demographic and education related and 23 items about knowledge on novel coronavirus). Multivariable logistic regression was performed using SPSS.Results The vast majority of students 228(75%) scored below 50% and were considered to have poor knowledge on COVID-19. Only 7.6% of participants knew that muscle pain is a symptom of 2019-nCoV infection. One hundred forty three (47%) of the participants did not know any symptoms of COVID-19. Only 24.3% of the respondents answered correctly that rubbing hands with alcohol based sanitizers can help in prevention of disease transmission. Sex, residence and social media use were significantly associated with adequate knowledge on novel coronavirus (p < 0.05).Conclusion Health science students had poor knowledge on COVID-19. The health science college and health authorities should re-examine their capability to manage the deadly virus
Knowledge regarding 2019 novel coronavirus (2019-nCoV) infection among final year health science students at Arbaminch College of Health Sciences, Southern Ethiopia: a cross-sectional study
OBJECTIVE: To assess the impact of carbapenem resistance and delayed appropriate antibiotic therapy (DAAT) on clinical and economic outcomes among patients with Enterobacterales infection. METHODS: This retrospective cohort study was conducted in a tertiary-care medical center in Thailand. Hospitalized patients with Enterobacterales infection were included. Infections were classified as carbapenem-resistant Enterobacterales (CRE) or carbapenem-susceptible Enterobacterales (CSE). Multivariate Cox proportional hazard modeling was used to examine the association between CRE with DAAT and 30-day mortality. Generalized linear models were used to examine length of stay (LOS) and in-hospital costs. RESULTS: In total, 4,509 patients with Enterobacterales infection (age, mean 65.2 18.7 years; 43.3% male) were included; 627 patients (13.9%) had CRE infection. Among these CRE patients, 88.2% received DAAT. CRE was associated with additional medication costs of $177 (95% confidence interval [CI], 114-239; P < .001) and additional in-hospital costs of $725 (95% CI, 448-1,002; P < .001). Patients with CRE infections had significantly longer LOS and higher mortality rates than patients with CSE infections: attributable LOS, 7.3 days (95% CI, 5.4-9.1; P < .001) and adjusted hazard ratios (aHR), 1.55 (95% CI, 1.26-1.89; P < .001). CRE with DAAT were associated with significantly longer LOS, higher mortality rates, and in-hospital costs. CONCLUSION: CRE and DAAT are associated with worse clinical outcomes and higher in-hospital costs among hospitalized patients in a tertiary-care hospital in Thailand.
Clinical and economic outcomes attributable to carbapenem-resistant Enterobacterales and delayed appropriate antibiotic therapy in hospitalized patients
Neutrophils have been suggested mediators of organ dysfunction in COVID-19. The current study investigated if systemic neutrophil activity, estimated by human neutrophil lipocalin (HNL) concentration in peripheral blood, is associated with acute kidney injury (AKI) development. A total of 103 adult patients admitted to intensive care, with PCR-confirmed SARS-CoV-2 infection, were prospectively included (Clinical Trials ID: NCT04316884). HNL was analyzed in plasma (P-HNL Dimer) and in whole blood (B-HNL). The latter after ex vivo activation with N-formyl-methionine-leucine-phenylalanine. All patients developed respiratory dysfunction and 62 (60%) were treated with invasive ventilation. Sixty-seven patients (65%) developed AKI, 18 (17%) progressed to AKI stage 3, and 14 (14%) were treated with continuous renal replacement therapy (CRRT). P-HNL Dimer was higher in patients with invasive ventilation, vasopressors, AKI, AKI stage 3, dialysis, and 30-day mortality (p < 0.001C0.046). B-HNL performed similarly with the exception of mild AKI and mortality (p < 0.001C0.004). The cohort was dichotomized by ROC estimated cutoff concentrations of 13.2 g/L and 190 g/L for P-HNL Dimer and B-HNL respectively. Increased cumulative risks for AKI, AKI stage 3, and death were observed if above the P-HNL cutoff and for AKI stage 3 if above the B-HNL cutoff. The relative risk of developing AKI stage 3 was nine and 39 times greater if above the cutoffs in plasma and whole blood, respectively, for CRRT eight times greater for both. In conclusion, systemically elevated neutrophil lipocalin, interpreted as increased neutrophil activity, was shown to be associated with an increased risk of severe AKI, renal replacement therapy, and mortality in COVID-19 patients with respiratory failure.
Systemic Human Neutrophil Lipocalin Associates with Severe Acute Kidney Injury in SARS-CoV-2 Pneumonia
Ndt80-like transcription factor Ron1 is best known for its essential role in the regulation of N-acetylglucosamine (GlcNAc) catabolism. Ron1 was again found to be essential for sensing GlcNAc in Beauveria bassiana. Importantly, our study revealed that Ron1 is involved in the metabolic processes of chitin and asexual development. To further investigate the novel functions of Ron1 in B. bassiana, extracellular chitinase activity in the Ron1 mutant was found to decrease by 84.73% compared with wild type. The deletion of Ron1 made it difficult for the fungus to accumulate intracellular GlcNAc. Furthermore, transcriptomic analysis revealed that Ron1 exerted a significant effect on global transcription and positively regulated genes encoding chitin metabolism in respond to chitin nutrition. Yeast one-hybrid assay confirmed that Ron1 could bind to specific cis-acting elements in the promoters of chitinase and hexokinase. In addition, Ron1 displayed an impaired chitin component of the cell wall, with a chitin synthetase (ChsVII) predicted to function downstream of Ron1. Finally, the virulence of Ron1 mutant was significantly reduced in the Galleria mellonella insect model through cuticle infection or cuticle bypassing infection. These data functionally characterize Ron1 in B. bassiana and expand our understanding of how the transcription factor Ron1 works in pathogens.
The transcription factor Ron1 is required for chitin metabolism, asexual development and pathogenicity in Beauveria bassiana, an entomopathogenic fungus
BACKGROUND: Most non-clinic based HIV pre-exposure prophylaxis (PrEP) programs require fingersticks to self-collect blood specimens for laboratory monitoring, a technique that often results in inadequate blood volume for quantitative syphilis and HIV serological testing. We evaluated the acceptability and feasibility of using the Tasso OnDemand? device as a self-sampling method for PrEP monitoring tests and compared results from samples obtained using the Tasso device to clinician-collected blood samples. METHODS: We enrolled study subjects online and in a sexual health clinic and HIV clinic in Seattle, WA, USA to assess the acceptability of blood self-sampling and preferences for home-based PrEP monitoring. We compared HIV antigen/antibody, quantitative rapid plasma reagin and creatinine results in paired self-collected and clinical specimens collected from a subset of participants. RESULTS: Of 141 participants, 124 (88%) were interested in collecting samples for PrEP monitoring at home. Among 48 who completed blood collections, 94% found the Tasso device easy to use and 95% felt they could perform self-sampling at home. Of 27 participants who used two devices, 100% collected sufficient blood to perform up to two tests while 33% collected sufficient serum for three tests. Agreement in test results between paired samples was high. CONCLUSIONS: These pilot data suggest that using the Tasso self-collection device is acceptable and could feasibly be used to obtain serum specimens sufficient for guideline-recommended PrEP monitoring, though use of a larger volume device may be preferable. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-022-07432-0.
Feasibility of a novel self-collection method for blood samples and its acceptability for future home-based PrEP monitoring
SARS-CoV-2 infection is characterized by a highly variable clinical course with patients experiencing asymptomatic infection all the way to requiring critical care support. This variation in clinical course has led physicians and scientists to study factors that may predispose certain individuals to more severe clinical presentations in hopes of either identifying these individuals early in their illness or improving their medical management. We sought to understand immunogenomic differences that may result in varied clinical outcomes through analysis of T-cell receptor sequencing (TCR-Seq) data in the open access ImmuneCODE database. We identified two cohorts within the database that had clinical outcomes data reflecting severity of illness and utilized DeepTCR, a multiple-instance deep learning repertoire classifier, to predict patients with severe SARS-CoV-2 infection from their repertoire sequencing. We demonstrate that patients with severe infection have repertoires with higher T-cell responses associated with SARS-CoV-2 epitopes and identify the epitopes that result in these responses. Our results provide evidence that the highly variable clinical course seen in SARS-CoV-2 infection is associated to certain antigen-specific responses.
Deep learning identifies antigenic determinants of severe SARS-CoV-2 infection within T-cell repertoires
Neuromyelitis optica spectrum disorder is an inflammatory autoimmune condition, predominantly affecting the optic nerves and spinal cord. It has been stated that viral infections play a role in the development of neuromyelitis optica. Several murine coronaviruses can cause inflammatory demyelinating diseases, including optic neuritis. Here we report, to the best of our knowledge, the first human case linking a presumed SARS-CoV-2 infection to the development of NMOSD.
Neuromyelitis optica spectrum disorder after presumed coronavirus (COVID-19) infection: A case report
The occurrence of COVID-19 pandemic has changed peoples life in every aspect, such as applying social distancing, the transition from offline to online activity are applied in order to decrease and stop the spread of the virus. This sudden change causes a fairly high level of anxiety and stress in society, especially for children because of activity restrictions. Various innovations, especially technology have been carried out to overcome the problems in distance restrictions that have arisen due to the COVID-19 pandemic. Virtual reality believes becoming one of the innovations that can be used to reduced anxiety levels and boredom during activity rectrictions, because it creates an artificial environment for humans to socialize. In this research, combine the Unity3D and blender software to build a virtual reality simulation with the help of virtual glassed to give a real impression of the virtual room that has been created. This VR application consists of three environments that children can use it to explore the virtual room without need being in crowded atmosphere. Based on the result of pretest and posttest questionnaire in 30 participants with the range age from seven to ten, it concludes that this VR applications can decrease the level of stress and anxiety in children by one to two levels. Besides that, this application located in acceptable area based on SUS score system.
Virtual Reality Simulation to Help Decrease Stress and Anxiety Feeling for Children during COVID-19 Pandemic
Abstract A competition ELISA utilizing a mAb directed towards a peplomer protein epitope common to TGEV, PRCV and related feline and canine coronaviruses is described.
An ELISA for the detection of serum antibodies to both transmissible gastroenteritis virus and porcine respiratory coronavirus
Patients with cancer are more at risk of quickly developing lethal forms of covid-19. Hospitals have therefore had to organise themselves to continue to receive patients while respecting the health measures. It was necessary to think about the best way of maintaining visits, as well as a means of adapting a specific space for palliative care and team thinking for patients cared for in identified palliative care beds.
[Identified palliative care beds in the time of COVID-19].
BACKGROUND: The clinical effectiveness of coronavirus disease 2019 (COVID-19) vaccination in kidney transplant (KT) recipients is lower than in the general population. METHODS: From April to October 2021, 481 KT recipients with COVID-19, included in the Spanish Society of Nephrology COVID-19 Registry, were analyzed. Data regarding vaccination status and vaccine type were collected, and outcomes of unvaccinated or partially vaccinated patients (n = 130) were compared with fully vaccinated patients (n = 351). RESULTS: Clinical picture was similar and survival analysis showed no differences between groups: 21.7% of fully vaccinated patients and 20.8% of unvaccinated or partially vaccinated died (P = 0.776). In multivariable analysis, age and pneumonia were independent risk factors for death, whereas vaccination status was not related to mortality. These results remained similar when we excluded patients with partial vaccination, as well as when we analyzed exclusively hospitalized patients. Patients vaccinated with mRNA-1273 (n = 213) showed a significantly lower mortality than those who received the BNT162b2 vaccine (n = 121) (hazard ratio: 0.52; 95% confidence interval, 0.31-0.85; P = 0.010). CONCLUSIONS: COVID-19 severity in KT patients has remained high and has not improved despite receiving 2 doses of the mRNA vaccine. The mRNA-1273 vaccine shows higher clinical effectiveness than BNT162b2 in KT recipients with breakthrough infections. Confirmation of these data will require further research taking into account the new variants and the administration of successive vaccine doses.
Breakthrough Infections Following mRNA SARS-CoV-2 Vaccination in Kidney Transplant Recipients
OBJECTIVE To report a single-center experience with laparoscopic simultaneous bilateral adrenalectomy (LSBA) and to evaluate its safety, surgical outcomes, and potential indications of the procedure. METHODS A total of 21 patients underwent LSBA between 2000 and 2010 at our institution. Four patients had bilateral Cushing's syndrome (CS), two had bilateral pheochromocytoma, and one had a bilateral metastatic tumor. Eleven patients had unilateral or bilateral aldosterone-producing adenoma (APA), associated with CS or subclinical CS. Three patients had unilateral APA with contralateral non-functioning adenoma. Partial adrenalectomy was performed first by using with four ports. After the excision of one gland, the contralateral gland was removed after repositioning of the patient. RESULTS LSBA was completed in all 21 patients without major complications. Mean operative time was 329.7 min and the estimated blood loss was 94.1 mL. Mean tumor size was 21.8 mm. Of the 16 patients receiving an adrenal-sparing procedure, nine of 11 discontinued glucocorticoid replacement after 2 years. The remaining five patients receiving bilateral total adrenalectomy required 0.5-0.75 mg of dexamethasone permanently. No open conversions, no deaths or no adrenal insufficiencies were encountered. CONCLUSIONS LSBA represents a safe and viable treatment option for selected patients with bilateral adrenal disease.
Laparoscopic simultaneous bilateral adrenalectomy: assessment of feasibility and potential indications.
Coronavirus disease 2019 (COVID-19) poses an occupational health risk to healthcare workers. Several thousand healthcare workers have already been infected, mainly in China. Preventing intra-hospital transmission of the communicable disease is therefore a priority. Based on the Systems Engineering Initiative for Patient Safety model, the strategies and measures to protect healthcare workers in an acute tertiary hospital are described along the domains of work task, technologies and tools, work environmental factors, and organizational conditions. The principle of zero occupational infection remains an achievable goal that all healthcare systems need to strive for in the face of a potential pandemic.
Preventing intra-hospital infection and transmission of COVID-19 in healthcare workers
BACKGROUND: Crohn's disease (CD) is an inflammatory bowel disease that causes inflammation and stricture, of any part of the mucosa and the gut wall. It forms skip lesions, sparing the areas in between the affected parts of the gastrointestinal tract. Crohn's disease could have one of three complications; fistula, intestinal obstruction due to stricture, or gastrointestinal inflammation presenting as severe diarrhoea. Stem cell therapy (SCT) is an innovative treatment that has been recently used in CD. The exact role of SCT in CD is still unclear. Stem cells modify the immunity of the patients or act as a "reset tool" for the immune system as in the case of systemically-injected stem cells, or regenerate the affected area of necrotic and inflammatory tissue as in the case of local injection into the lesion. Stem cells are a wide variety of cells including pluripotent stem cells or differentiated stem cells. The hazards range from rejection to symptomatic manifestations as fever or increase infection. OBJECTIVES: The objective of this Cochrane systematic review is to assess the effects of stem cell transplantation compared to standard of care alone or with placebo on efficacy and safety outcomes in patients with refractory CD. SEARCH METHODS: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and clinical trial registries (Clinicaltrials.gov, World Health Organization-International Clinical Trials Registry Platform WHO ICTRP) from inception to 19 March 2021, without any language, publication year, or publication status restrictions. In addition, we searched references of included studies and review articles for further references. An update of the published studies was done during the writing of the review. SELECTION CRITERIA: We included only randomised controlled trials (RCTs) that assessed the effectiveness and safety of SCT in refractory CD versus standard care alone (control) or with placebo. DATA COLLECTION AND ANALYSIS: Two review authors (SEN and SFA) independently screened the studies retrieved from the search results for inclusion, extracted data and assessed the risk of bias. Any disagreement was resolved through a consensus between the authors. We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We conducted our search on 19 March 2021 and identified 639 records. We added two records by a manual search of the published reviews on the topic to a total of 641 records. The Covidence program removed 125 duplicates making a total of 516 reports. Two review authors (SEN and SFA) screened titles and abstracts and excluded 451 records with the remaining 65 for full-text records screened independently by the two authors; only 18 studies were considered for inclusion. We included seven RCTs with a total of 442 participants for the meta-analysis. The intervention group included 234 patients, and the control group included 208 patients. Nine trials are ongoing and, two abstracts are awaiting classification. All patients in the control and intervention groups received the standard therapy for CD. Only three studies used blinding methods for the control group in the form of a placebo, with one study of the three stated that the blinding method was inefficient. The patients and personnel were aware of the intervention in the rest of the four studies as they were open-label trials. However, the effect of unblinding was balanced by the low risk of detection bias in five of the included studies. The evidence is uncertain about the effect of SCT on achieving clinical remission as compared to control/placebo (risk ratio (RR) 1.88, 95% Confidence Interval (CI) 0.80 to 4.41; 3 studies; low-certainty evidence). The evidence is very uncertain about the effect of SCT on achieving Crohn's Disease Activity Index (CDAI) <150 at 24 weeks compared to control (RR1.02 95% CI 0.67 to 1.56; 4 studies; very-low certainty evidence). SCT is likely to achieve fistula closure as compared to the control/placebo both in the short term (RR 1.48, 95% CI 1.12 to 1.96); low-certainty evidence) and in the long term (RR 1.42, 95% CI 1.09 to 1.87; 4 studies; low-certainty evidence) follow-up. The evidence is very uncertain about the effect of SCT to cause no difference in the number of total adverse events as compared to the control/placebo (RR 0.99, 95% CI [0.88 to 1.13); 4 studies; very-low-certainty evidence). However, SCT is likely to increase the number of serious adverse events as compared to the control/placebo (RR 1.22, 95% CI 0.88 to 1.67; 7 studies; low-certainty evidence). The evidence is very uncertain about the effect of SCT to decrease the withdrawal due to adverse events as compared to the control/placebo (RR 0.78, 95% CI 0.32 to 1.89; 3 studies; very-low certainty evidence). Funding by pharmaceutical companies was found in three studies, with one including more than 50% of our studied population. AUTHORS' CONCLUSIONS: SCT shows an uncertain effect on clinical remission with low certainty of evidence. SCT shows an uncertain effect on CDAI score to reach <150 after 24 weeks of treatment, with very low certainty evidence. SCT shows beneficial effects on fistula-closure during short and long-term follow-up with low-certainty evidence in both outcomes. There was no change in the total number of adverse events with SCT as compared to control, with very low certainty evidence. While there was a moderate effect on increasing the number of serious adverse events in the SCT group, as compared to the control with low-certainty evidence. Withdrawal due to adverse events was slightly higher in the control group with very low certainty evidence. All the participants were refractory to standard medical treatment, but the number of participants was small, this may limit the generalizability of the results. Further research is needed for validation. More objective outcomes are needed in the assessment of stem cell effectiveness in the treatment of Crohn's disease, especially the intestinal CD subtype; with standardization of the dose, methods of stem cell preparation, route of administration, and inclusion criteria to the studies to achieve clear results.
Stem cell transplantation for induction of remission in medically refractory Crohn's disease
BACKGROUND: Trimethylamine N-oxide (TMAO) is a microbiota-derived metabolite, which is linked to vascular inflammation and atherosclerosis in cardiovascular (CV) diseases. But its effect in infectious diseases remains unclear. We conducted a single-center prospective study to investigate association of TMAO with in-hospital mortality in septic patients admitted to an intensive care unit (ICU). METHODS: Totally 95 septic, mechanically ventilated patients were enrolled. Blood samples were obtained within 24 h after ICU admission, and plasma TMAO concentrations were determined. Septic patients were grouped into tertiles according to TMAO concentration. The primary outcome was in-hospital death, which further classified as CV and non-CV death. Besides, we also compared the TMAO concentrations of septic patients with 129 non-septic patients who were admitted for elective coronary angiography (CAG). RESULTS: Septic patients had significantly lower plasma TMAO levels than did subjects admitted for CAG (1.0 vs. 3.0 mol/L, p < 0.001). Septic patients in the lowest TMAO tertile (< 0.4 mol/L) had poorer nutrition status and were given longer antibiotic courses before ICU admission. Circulating TMAO levels correlated positively with daily energy intake, the albumin and prealbumin concentration. Compared with those in the highest TMAO tertile, septic patients in the lowest TMAO tertile were at greater risk of non-CV death (hazard ratio 2.51, 95% confidence interval 1.21C5.24, p = 0.014). However, TMAO concentration was no longer an independent predictor for non-CV death after adjustment for disease severity and nutritional status. CONCLUSION: Plasma TMAO concentration was inversely associated with non-CV death among extremely ill septic patients, which could be characterized as TMAO paradox. For septic patients, the impact of malnutrition reflected by circulating TMAO levels was greater than its pro-inflammatory nature. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40560-021-00581-5.
Paradox of trimethylamine-N-oxide, the impact of malnutrition on microbiota-derived metabolites and septic patients