Anxiety among hospitalized COVID-19 patients: a case-control study from a tertiary teaching hospital in Malaysia.

Introduction: Anxiety has been increasingly recognized as part of the psychosocial health issues in COVID-19 patients. However, the impact of this topic may be underestimated in low- and middle-income countries. This study aimed to estimate the prevalence of and risk factors of anxiety in COVID-19 patients compared to controls in a local tertiary teaching hospital in Malaysia. Methods: In this case-control study, we analyzed data on adult patients aged 18 years and above hospitalized for COVID-19 infection with matched hospitalized controls. The demographic, clinical data and anxiety measures using the Generalized Anxiety Disorder-7 questionnaire were analyzed using univariate and multivariate analysis. Results: 86.6% in the COVID-19 group had anxiety, significantly higher than 13.4% in the control group (p = 0.001). The COVID-19 group was significantly associated with the GAD-7 severity (p = 0.001). The number of COVID-19 patients in the mild, moderate, and severe anxiety groups was 48 (84.2%), 37 (86%), and 18 (94.7%), respectively. Multiple logistic regression showed significant predictors for anxiety, including COVID-19 diagnosis and neurological symptoms. Anxiety was found 36.92 times higher in the patients with COVID-19 compared to those without COVID-19 (OR 36.92;95% CI 17.09, 79.78, p = 0.001). Patients with neurological symptoms were at risk of having anxiety (OR 2.94; 95% CI 1.03, 8.41, p = 0.044). Discussion: COVID-19 patients experience a significant disruption in psychosocial functioning due to hospitalization. The burden of anxiety is notably high, compounded by a diagnosis of COVID-19 itself and neurological symptomatology. Early psychiatric referrals are warranted for patients at risk of developing anxiety symptoms.

Potential influence of COVID-19 and dexamethasone on the reproductive system: what we know and can expect.

Dexamethasone is the first and an important therapy that significantly reduces the risk of death in patients with severe COVID-19 disease. Nevertheless, a lot of studies have revealed that it has adverse impacts on multiple systems of the body especially the reproductive system, and dexamethasone exposure during the human foetal period may be associated with various diseases. In this paper, we reviewed the literature regarding the adverse effects of COVID-19 and dexamethasone administration on the reproductive system as well as related disease pathogenesis, in an attempt to clarify the potential harms of dexamethasone treatment in COVID-19 patients. Overall, we strongly support the application of dexamethasone as a pharmaceutical therapy in critical COVID-19 patients before a better therapy is developed, but the adverse side effects that may arise cannot be ignored. Our review will help medical professionals in the prognosis and follow-up of patients treated with dexamethasone. In addition, given that a considerable amount of uncertainty, confusion and even controversy that still remains, further studies and more clinical trials are urgently needed to improve the understanding of the parameters and the effects of dexamethasone on reproductive function of patients with severe acute respiratory syndrome coronavirus 2 infection.

The extent of the shock to economic growth by the epidemic and the recovery effect: evidence from China since 2020

The Covid-19 pandemic has exerted significant downward pressure on economic activity. In this paper, we examine the extent of the epidemic shock and recovery effects on economic growth by province in China since 2020. We find that the extent of the epidemic shock on economic growth in China has been gradually weakening. Still, the economy has not yet fully recovered from the shock. Also, there is some heterogeneity across provinces in the extent to the economic growth shocked by epidemic and the recovery effects.

Effects of COVID-19 and mRNA vaccines on human fertility.

The coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has precipitated a global health crisis of unprecedented proportions. Because of its severe impact, multiple COVID-19 vaccines are being rapidly developed, approved and manufactured. Among them, mRNA vaccines are considered as ideal candidates with special advantages to meet this challenge. However, some serious adverse events have been reported after their application, significantly increasing concerns about the safety and efficacy of the vaccines and doubts about the necessity of vaccination. Although several fertility societies have announced that COVID-19 mRNA vaccines are unlikely to affect fertility, there is no denying that the current evidence is very limited, which is one of the reasons for vaccine hesitancy in the population, especially in pregnant women. Herein, we provide an in-depth discussion on the involvement of the male and female reproductive systems during SARS-CoV-2 infection or after vaccination. On one hand, despite the low risk of infection in the male reproductive system or fetus, COVID-19 could pose an enormous threat to human reproductive health. On the other hand, our review indicates that both men and women, especially pregnant women, have no fertility problems or increased adverse pregnancy outcomes after vaccination, and, in particular, the benefits of maternal antibodies transferred through the placenta outweigh any known or potential risks. Thus, in the case of the rapid spread of COVID-19, although further research is still required, especially a larger population-based longitudinal study, it is obviously a wise option to be vaccinated instead of suffering from serious adverse symptoms of virus infection.

Effect of COVID-19 on sperm parameters: pathologic alterations and underlying mechanisms.

The rapid outbreak of the coronavirus disease 2019 (COVID-19) pandemic has brought challenges to different medical fields, especially reproductive health. To date, most studies on the effects of COVID-19 on male reproduction have some limitations. In addition, there is little research on the mechanisms underlying by which severe acute respiratory syndrome coronavirus 2 infection affects semen quality. Here, we revealed the possible impact of COVID-19 on sperm parameters and the potential mechanisms. At present, it is still controversial whether COVID-19-induced fever adversely affects sperm parameters. Severe acute respiratory syndrome coronavirus 2 can induce up-regulation of pro-inflammatory cytokine, which leads to the destruction of blood-testis barrier and impairment of spermatogenesis. Moreover, severe viral infection of the respiratory system could induce systemic oxidative stress. Sperm are highly vulnerable to it due to their limited levels of antioxidant defense, unsophisticated DNA damage detection and repair mechanisms. Our review prompt medical staff and patients to consciously check the reproductive function of COVID-19 male patients. Moreover, opening our prospective beyond the direct infection could be the key to better understand the COVID-19 short and long-term effects and provide a new idea for future treatment of patients with reproductive function injury.

IL-10 Promotes CXCL13 Expression in Macrophages Following Foot-and-Mouth Disease Virus Infection.

Foot-and-mouth disease (FMD) is one of the most contagious livestock diseases in the world, posing a constant global threat to the animal trade and national economies. The chemokine C-X-C motif chemokine ligand 13 (CXCL13), a biomarker for predicting disease progression in some diseases, was recently found to be increased in sera from mice infected with FMD virus (FMDV) and to be associated with the progression and severity of the disease. However, it has not yet been determined which cells are involved in producing CXCL13 and the signaling pathways controlling CXCL13 expression in these cells. In this study, the expression of CXCL13 was found in macrophages and T cells from mice infected with FMDV, and CXCL13 was produced in bone-marrow-derived macrophages (BMDMs) by activating the nuclear factor-kappaB (NF-κB) and JAK/STAT pathways following FMDV infection. Interestingly, CXCL13 concentration was decreased in sera from interleukin-10 knock out (IL-10-/-) mice or mice blocked IL-10/IL-10R signaling in vivo after FMDV infection. Furthermore, CXCL13 was also decreased in IL-10-/- BMDMs and BMDMs treated with anti-IL-10R antibody following FMDV infection in vitro. Lastly, it was demonstrated that IL-10 regulated CXCL13 expression via JAK/STAT rather than the NF-κB pathway. In conclusion, the study demonstrated for the first time that macrophages and T cells were the cellular sources of CXCL13 in mice infected with FMDV; CXCL13 was produced in BMDMs via NF-κB and JAK/STAT pathways; and IL-10 promoted CXCL13 expression in BMDMs via the JAK/STAT pathway.

Female reproductive health during the COVID-19 pandemic: latest evidence and understanding.

PURPOSE: The ongoing coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has imposed a heavy burden on medical systems. In addition to the respiratory system, the virus also causes injuries to other organs and systems such as the gastroenteric system, kidneys, and reproductive system. Female reproductive health requires more attention in this context. METHODS: We have performed a thorough review of the relevant literature that addresses the impacts of SARS-CoV-2 infection and COVID-19 vaccination on the female reproductive system. RESULTS: Most evidence shows that SARS-CoV-2 does not infect the female reproductive system. However, the virus may indirectly influence sex hormone concentrations through inflammation associated with cytokine storms and nervous system damage. Menstrual disorders in women infected with SARS-CoV-2 may be caused by down-regulation of angiotensin-converting enzyme 2, abnormal hormone levels, medications, and stress. There is no significant difference in ovarian follicle quality and in vitro fertilization parameters between the pre- and post-COVID-19 vaccination groups. In addition, most symptoms due to side effects of vaccination could recover within a short period of time. CONCLUSION: SARS-CoV-2 infection affects female reproductive system function through multiple mechanisms. It is recommended that women of childbearing age be vaccinated with COVID-19 vaccine.

Vaccine inequity-induced COVID-19 dilemma: Time to sober up.

UNSTRUCTURED: The ongoing coronavirus disease 2019 pandemic has not only posed a serious threat to public health but has also imposed a heavy burden on medical systems and global economies. To combat this challenge, unprecedented efforts have been made by governments and the scientific community in the development and production of vaccines. As a result, less than a year elapsed between identification of a novel pathogen sequence and large-scale vaccine rollout. However, much of the focus and debate has increasingly shifted to the looming risk of global vaccine inequity and whether we could do more to modify this risk. In this paper, we first outline the scope of inequitable vaccine distribution and identify its truly catastrophic consequences. Then, from the perspectives of political will, free markets and profit-driven enterprises based on patent and intellectual property protection, we analyze in-depth the root causes why this phenomenon is so difficult to combat. Apart from these, some specific and crucial solutions that should be undertaken in the long term were also put forward, in order to provide a useful reference for the authorities, stakeholders and researchers involved in addressing this global crisis and the next one.

A Multi-Site Survey Study on the Association Between the COVID-19 Pandemic and United States Anesthesiology Residents' Mental Health.

BACKGROUND:  At the onset of the coronavirus disease 2019 (COVID-19) pandemic, anesthesiology residency programs were impacted differently due to various factors such as the local severity of COVID-19, exposure to patient suffering, and inability to complete rotations. We sought to investigate the impact of local-level pandemic severity on the well-being of anesthesiology residents. METHODS:  This multi-site study surveyed postgraduate year two residents from 15 United States (US) anesthesiology programs using the Perceived Stress Scale, Mini-Z, Patient Health Questionnaire-9,WHO-5 Well-Being Index,and the Multidimensional Scale of Perceived Social Support before the pandemic (baseline survey) and during the first COVID-19 surge (post survey). RESULTS:  A total of 144 (65%) residents responded to the initial baseline survey; 73 (33%) responded to the post survey, and 49 (22%) completed both surveys. There was not a statistically significant difference in any well-being outcomes of participants between the surveys, nor was there a significant difference based on the severity of COVID-19 impact at the program's hospital. Male participants had higher perceived stress scores (ß = 4.05, 95%CI: 0.42, 7.67, P = 0.03) and lower social support from family (ß = -6.57, 95%CI: -11.64, -1.51, P = 0.01) at the post survey compared to female participants after controlling for baseline scores. Additionally, married participants or those with domestic partners reported higher perceived social support in the post survey (ß = 5.79, 95%CI: -0.65, 12.23, P = 0.03). CONCLUSION:  The local COVID-19 severity at a residency program did not disproportionately impact well-being scores among anesthesiology residents. Those most vulnerable to diminished well-being appeared to be male and single participants. As a result, targeted well-being interventions, including those aiming to increase social support, to higher-risk resident groups may be indicated. Future work is needed to assess the longstanding COVID-19 pandemic impacts on resident well-being.

Therapeutic Polypeptides and Peptidomimetics: Powerful Tools for COVID-19 Treatment.

The coronavirus disease 2019 (COVID-19) pandemic has swept the whole world and brought about a public health crisis of unprecedented proportions. To combat the rapid transmission and possible deaths due to the disease, researchers and companies around the world are developing all possible strategies. Due to the advantages of safety, specificity, and fewer adverse effects, polypeptide and peptidomimetic drugs are considered promising strategies. This review comprehensively summarizes and discusses the progress in development of peptide drugs for use in the treatment of COVID-19. Based on the latest results in this field, we divided them into clinically approved drugs, clinical trial drugs, and clinically ineffective drugs, and outlined the molecular targets and mechanisms of action one by one to reveal their feasibility as promising therapeutic agents for COVID-19. Notably, monoclonal antibodies have shown beneficial effects in the early stages of infection, while Paxlovid can significantly reduce hospitalization and mortality among non-vaccinated patients. Among clinical experimental drugs, both the interleukin-1 receptor antagonist anakinra and the bradykinin B2 receptor antagonist icatibant are well tolerated and effective in patients with COVID-19, but long-term trials are needed to confirm the durability of efficacy.

Vaccination options for pregnant women during the Omicron period.

Omicron exhibits reduced pathogenicity in general population than the previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. However, the severity of disease and pregnancy outcomes of Omicron infection among pregnant women have not yet been definitively established. Meanwhile, substantial proportions of this population have doubts about the necessity of vaccination given the reports of declining efficacy of coronavirus disease 2019 (COVID-19) vaccines. Herein, we comprehensively discuss the clinical outcomes of infected pregnant women during the Omicron period and summarize the available data on the safety and efficacy profile of COVID-19 vaccination. The results found that the incidence of moderate and severe disease, maternal mortality, pregnancy loss, preterm delivery, stillbirth, preeclampsia/eclampsia, and gestational hypertension during the Omicron period are similar to those during the Pre-Delta period. In view of the effects of mass vaccination and previous natural infection on disease severity, the virulence of Omicron in pregnant women may be comparable to or even higher than that of the Pre-Delta variant. Moreover, the currently approved COVID-19 vaccines are safe and effective for pregnant women. Particularly, those who received a second or third dose had significantly less severe disease with little progression to critical illness or death compared with those who were unvaccinated or received only one dose. Therefore, in the case of the rapid spread of Omicron, pregnant women should still strictly follow preventive measures to avoid infection and receive the COVID-19 vaccine in a timely manner.

Effects of inactivated SARS-CoV-2 vaccination on male fertility: a retrospective cohort study.

BACKGROUND: Numerous studies have revealed severe damage to male fertility from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, raising concerns about the potential adverse impact on reproductive function of the coronavirus disease 2019 (COVID-19) vaccine developed based on the virus. Interestingly, there are several researchers who have studied the impact of the COVID-19 mRNA vaccine since then but have come up with conflicting results. As a near-ideal candidate for mass immunization programs, inactivated SARS-CoV-2 vaccine has been widely used in many countries, particularly in less wealthy nations. However, little is known about its effect on male fertility. METHODS: Here, we conducted a retrospective cohort study at a single large center for reproductive medicine in China between December 2021 and August 2022. 519 fertile men with no history of laboratory-confirmed COVID-19 were included and categorized into four groups based on their vaccination status: unvaccinated group (n=168), one-dose vaccinated group (n=8), fully vaccinated group (n=183), and booster group (n=160). All of them underwent a semen analysis and most had serum sex hormone levels tested. RESULTS: There were no significant differences in all semen parameters and sex hormone levels between the unvaccinated group and either vaccinated group. To account for possible vaccination-to-test interval-specific changes, sub-analyses were performed for two interval groups: ≤90 and >90 days. As expected, most of the semen parameters and sex hormone levels remained unchanged between the control and vaccinated groups. However, participants in vaccinated group (≤90 days) have decreased total sperm motility and increased FSH level compared with the ones in unvaccinated group. Moreover, some trends similar to those found during COVID-19 infection and recovery were observed in our study. Fortunately, all values are within the normal range. In addition, vaccinated participants reported few adverse reactions. No special medical intervention was required, and no serious adverse reactions happened. CONCLUSION: Our study suggests that inactivated SARS-CoV-2 vaccination does not impair male fertility, possibly due to the low frequency of adverse effects. This information reassures young male population who got this vaccine worldwide, and helps guide future vaccination efforts. This article is protected by copyright. All rights reserved.

Neurological manifestations in SARS-CoV-2 infection: A single-center cross-sectional study in Malaysia.

Background: Neurological involvement associated with SARS-CoV-2 infection has been reported from different regions of the world. However, data from South East Asia are scarce. We described the neurological manifestations and their associated factors among the hospitalized COVID-19 patients from an academic tertiary hospital in Malaysia. Methods: A cross-sectional observational study of hospitalized COVID-19 patients was conducted. The neurological manifestations were divided into the self-reported central nervous system (CNS) symptoms, stroke associated symptoms, symptoms of encephalitis or encephalopathy and specific neurological complications. Multiple logistic regression was performed using demographic and clinical variables to determine the factors associated with outcome. Results: Of 156 hospitalized COVID-19 patients with mean age of 55.88 ± 6.11 (SD) years, 23.7% developed neurological complications, which included stroke, encephalitis and encephalopathy. Patients with neurological complications were more likely to have diabetes mellitus (p = 0.033), symptoms of stroke [limb weakness (p < 0.001), slurred speech (p < 0.001)]; and encephalitis or encephalopathy [confusion (p < 0.001), forgetfulness (p = 0.006) and seizure (p = 0.019)]. Unvaccinated patients had a 4.25-fold increased risk of having neurological complications (adjusted OR = 4.25; 95% CI: 1.02, 17.71, p = 0.047). Anosmia and dysgeusia were less associated with neurological complications (adjusted OR = 0.22; 95% CI: 0.05, 0.96, p = 0.044). The odds of neurological complications were increased by 18% in patients with leukocytosis (adjusted OR = 1.18, 95% CI: 1.003, p = 0.0460). Conclusions: Stroke, encephalitis and encephalopathy were the common neurological complications from our study. Diabetes mellitus, presence of symptoms of stroke, symptoms of encephalitis or encephalopathy, leukocytosis, and being unvaccinated against COVID-19 were the associated risk factors of developing neurological complications.

Serum Proteomic Analysis for New Types of Long-Term Persistent COVID-19 Patients in Wuhan.

The emergence of a new type of COVID-19 patients, who were retested positive after hospital discharge with long-term persistent SARS-CoV-2 infection but without COVID-19 clinical symptoms (hereinafter, LTPPs), poses novel challenges to COVID-19 treatment and prevention. Why was there such a contradictory phenomenon in LTPPs? To explore the mechanism underlying this phenomenon, we performed quantitative proteomic analyses using the sera of 12 LTPPs (Wuhan Pulmonary Hospital), with the longest carrying history of 132 days, and mainly focused on 7 LTPPs without hypertension (LTPPs-NH). The results showed differential serum protein profiles between LTPPs/LTPPs-NH and health controls. Further analysis identified 174 differentially-expressed-proteins (DEPs) for LTPPs, and 165 DEPs for LTPPs-NH, most of which were shared. GO and KEGG analyses for these DEPs revealed significant enrichment of "coagulation" and "immune response" in both LTPPs and LTPPs-NH. A unity of contradictory genotypes in the 2 aspects were then observed: some DEPs showed the same dysregulated expressed trend as that previously reported for patients in the acute phase of COVID-19, which might be caused by long-term stimulation of persistent SARS-CoV-2 infection in LTPPs, further preventing them from complete elimination; in contrast, some DEPs showed the opposite expression trend in expression, so as to retain control of COVID-19 clinical symptoms in LTPPs. Overall, the contrary effects of these DEPs worked together to maintain the balance of LTPPs, further endowing their contradictory steady-state with long-term persistent SARS-CoV-2 infection but without symptoms. Additionally, our study revealed some potential therapeutic targets of COVID-19. Further studies on these are warranted. IMPORTANCE This study reported a new type of COVID-19 patients and explored the underlying molecular mechanism by quantitative proteomic analyses. DEPs were significantly enriched in "coagulation" and "immune response". Importantly, we identified 7 "coagulation system"- and 9 "immune response"-related DEPs, the expression levels of which were consistent with those previously reported for patients in the acute phase of COVID-19, which appeared to play a role in avoiding the complete elimination of SARS-CoV-2 in LTPPs. On the contrary, 6 "coagulation system"- and 5 "immune response"-related DEPs showed the opposite trend in expression. The 11 inconsistent serum proteins seem to play a key role in the fight against long-term persistent SARS-CoV-2 infection, further retaining control of COVID-19 clinical symptom of LTPPs. The 26 proteins can serve as potential therapeutic targets and are thus valuable for the treatment of LTPPs; further studies on them are warranted.

The importance of booster vaccination in the context of Omicron wave.

Omicron (B.1.1.529) was first detected in a sample collected in Botswana on November 11, 2021, and has rapidly replaced Delta as the dominant global variant given the robust transmissibility. Moreover, it displays a lower virulence than other variants. However, the pathogenicity of Omicron appears to be underestimated in view of the increasing levels of herd immunity through natural infection or vaccination. Additionally, the volume of hospitalizations and deaths increase in proportion to the number of cases due to the high transmissibility of Omicron. Therefore, vaccination remains an important public health priority. Notably, a series of important mutations in the Omicron spike protein, especially in the receptor-binding domain and N-terminal domain, appears to be associated with immune escape capacity, reducing the willingness of people to receive vaccines. Herein, we provide an in-depth discussion to assess the effectiveness of the second and third vaccination against Omicron variant. On the one hand, the two-dose vaccination program adopted by many countries is insufficient to prevent Omicron infection given the mutations correlated with immune escape and the decline in vaccine efficacy over time. On the other hand, booster dose significantly increases the protective efficacy against Omicron infection. Most importantly, heterologous third dose vaccination induces a more robust immune response than homologous booster dose. Therefore, under the special background of this pandemic, there is an urgent need to accelerate the third dose of vaccination, especially providing better booster vaccination strategies, to combat emerging Omicron variant.

Clinical analysis on clinical value of initial chest CT findings in patients with COVID-19

Objective: To assess the clinical value of initial chest CT findings in patients with COVID-19.

Semen parameters and sex hormones as affected by SARS-CoV-2 infection: A systematic review Paramètres du sperme et hormones sexuelles affectés par l’infection par le SRAS-CoV-2: une revue systématique

Background Impaired semen quality and reproductive hormone levels were observed in patients during and after recovery from coronavirus disease 2019 (COVID-19), which raised concerns about negative effects on male fertility. Therefore, this study systematically reviews available data on semen parameters and sex hormones in patients with COVID-19. Methods Systematic search was performed on PubMed and Google Scholar until July 18, 2022. We identified relevant articles that discussed the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on male fertility. Results A total number of 1684 articles were identified by using a suitable keyword search strategy. After screening, 26 articles were considered eligible for inclusion in this study. These articles included a total of 1960 controls and 2106 patients. When all studies were considered, the results showed that the semen parameters and sex hormone levels of patients infected with SARS-CoV-2 exhibited some significant differences compared with controls. Fortunately, these differences gradually disappear as patients recover from COVID-19. Conclusion While present data show the negative effects of SARS-CoV-2 infection on male fertility, this does not appear to be long-term. Semen quality and hormone levels will gradually increase to normal as patients recover.

Combining metabolome and clinical indicators with machine learning provides some promising diagnostic markers to precisely detect smear-positive/negative pulmonary tuberculosis.

BACKGROUND: Tuberculosis (TB) had been the leading lethal infectious disease worldwide for a long time (2014-2019) until the COVID-19 global pandemic, and it is still one of the top 10 death causes worldwide. One important reason why there are so many TB patients and death cases in the world is because of the difficulties in precise diagnosis of TB using common detection methods, especially for some smear-negative pulmonary tuberculosis (SNPT) cases. The rapid development of metabolome and machine learning offers a great opportunity for precision diagnosis of TB. However, the metabolite biomarkers for the precision diagnosis of smear-positive and smear-negative pulmonary tuberculosis (SPPT/SNPT) remain to be uncovered. In this study, we combined metabolomics and clinical indicators with machine learning to screen out newly diagnostic biomarkers for the precise identification of SPPT and SNPT patients. METHODS: Untargeted plasma metabolomic profiling was performed for 27 SPPT patients, 37 SNPT patients and controls. The orthogonal partial least squares-discriminant analysis (OPLS-DA) was then conducted to screen differential metabolites among the three groups. Metabolite enriched pathways, random forest (RF), support vector machines (SVM) and multilayer perceptron neural network (MLP) were performed using Metaboanalyst 5.0, "caret" R package, "e1071" R package and "Tensorflow" Python package, respectively. RESULTS: Metabolomic analysis revealed significant enrichment of fatty acid and amino acid metabolites in the plasma of SPPT and SNPT patients, where SPPT samples showed a more serious dysfunction in fatty acid and amino acid metabolisms. Further RF analysis revealed four optimized diagnostic biomarker combinations including ten features (two lipid/lipid-like molecules and seven organic acids/derivatives, and one clinical indicator) for the identification of SPPT, SNPT patients and controls with high accuracy (83-93%), which were further verified by SVM and MLP. Among them, MLP displayed the best classification performance on simultaneously precise identification of the three groups (94.74%), suggesting the advantage of MLP over RF/SVM to some extent. CONCLUSIONS: Our findings reveal plasma metabolomic characteristics of SPPT and SNPT patients, provide some novel promising diagnostic markers for precision diagnosis of various types of TB, and show the potential of machine learning in screening out biomarkers from big data.

Probiotics for the prevention of Hirschsprung-associated enterocolitis.

BACKGROUND: Hirschsprung-associated enterocolitis (HAEC) is a leading cause of serious morbidity and potential mortality in children with Hirschsprung's disease (HD). People with HAEC suffer from intestinal inflammation, and present with diarrhoea, explosive stools, and abdominal distension. Probiotics are live microorganisms with beneficial health effects, which can optimise gastrointestinal function and gut flora. However, the efficacy and safety of probiotic supplementation in the prevention of HAEC remains unclear. OBJECTIVES: To assess the effects of probiotic supplements used either alone or in combination with pharmacological interventions on the prevention of Hirschsprung-associated enterocolitis. SEARCH METHODS: We searched CENTRAL, PubMed, Embase, the China BioMedical Literature database (CBM), the World Health Organization International Clinical Trials Registry, ClinicalTrials.gov, the Chinese Clinical Trials Registry, Australian New Zealand Clinical Trials Registry, and Clinical Trials Registry-India, from database inception to 27 February 2022. We also searched the reference lists of relevant articles and reviews for any additional trails. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing probiotics and placebo, or any other non-probiotic intervention, for the prevention of HAEC were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the risk of bias of the included studies; disagreements were resolved by discussion with a third review author. We assessed the certainty of evidence using the GRADE approach. We calculated odds ratios (ORs) with 95% confidence intervals (CIs) for dichotomous outcomes. MAIN RESULTS: We included two RCTs, with a total of 122 participants. We judged the overall risk of bias as high. We downgraded the evidence due to risk of bias (random sequence generation, allocation concealment, and blinding) and small sample size. The evidence is very uncertain about the effect of probiotics on the occurrence of HAEC (OR 0.58, 95% CI 0.10 to 3.43; I² = 74%; 2 studies, 120 participants; very low-certainty evidence). We found one included study that did not measure serious adverse events and one included study that reported no serious adverse events related to probiotics. Probiotics may result in little to no difference between probiotics and placebo in relation to the severity of children with HAEC at Grade I (OR 0.66, 95% CI 0.14 to 3.16; I² = 25%; 2 studies, 120 participants; low-certainty evidence). The effects of probiotics on the severity of HAEC at Grade II are very uncertain (OR 1.14, 95% CI 0.01 to 136.58; I² = 86%; 2 studies, 120 participants; very low-certainty evidence). Similarly, the evidence suggests that probiotics results in little to no difference in relation to the severity of HAEC at Grade III (OR 0.43, 95% CI 0.05 to 3.45; I² = 0%; 2 studies, 120 participants; low-certainty evidence). No overall mortality or withdrawals due to adverse events were reported. Probiotics may result in little to no difference in the recurrence of episodes of HAEC compared to placebo (OR 0.85, 95% CI 0.24 to 3.00; 1 study, 60 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: There is currently not enough evidence to assess the efficacy or safety of probiotics for the prevention of Hirschsprung-associated enterocolitis when compared with placebo. The presence of low- to very-low certainty evidence suggests that further well-designed and sufficiently powered RCTs are needed to clarify the true efficacy of probiotics.