Anti-Toxoplasma gondii Activity of Curcumin: A Systematic Review of Pre-clinical Studies.

OBJECTIVE: This study has focused on anti-Toxoplasma gondii activity of curcumin. METHODS: In this systematic review, anti-parasitic activity of Curcuma longa on Toxoplasma gondii was assessed. Therefore, several databases, including PubMed, Scopus, Web of Science, Embase and Google Scholar, were searched from 2010 to 2020. RESULTS: Of the 2200 papers retrieved between 2010 and 2020, six articles were reliable and were scrutinized. In 2 in vitro studies, the most used strain was the RH strain of Toxoplasma gondii, whereas among 4 in vivo studies, RH strain was found in 2 (50%) studies, Me49 strain in 1(25%) study, and RH and Me49 strain in 1 (25%) study. In four in vivo studies, the most used animal model was BALB/c, and Swiss albino was found in 1 study (25%) and Albino rats in 1 study (25%). CONCLUSION: Curcumin and nanoparticles formulated with curcumin are new and useful agents for the treatment of parasitic diseases and reduction of drug resistance. The success of this therapeutic approach stems from the specific action of Curcuma longa against parasites and pathogens.

In Vivo and In Vitro Anti-schistosomiasis Effect of Garlic: A Systematic Review.

BACKGROUND: Garlic (Allium sativum) is used as a natural supplement for the treatment of various diseases and disorders because it has antibacterial, antiviral, antifungal, antiparasitic, antioxidant, and anti-inflammatory properties. This systematic review aimed to evaluate in vitro and in vivo effects of garlic against Schistosoma spp. METHODS: The current study was carried out according to the PRISMA guidelines and registered in the CAMARADES-NC3Rs Preclinical Systematic Review and Meta-analysis Facility [SyRF] database. The literature search was conducted using five databases, including Scopus, PubMed, Web of Science, Embase, and Google Scholar, from January 2008 to January 2021. The search was restricted to articles published in the English language. Syntax was performed based on each database tag. RESULTS: Out of 2,600 studies, 10 met the eligibility criteria for review. The examined parasite in all studies was Schistosoma mansoni. Ten studies (90%) were performed in vivo and one study in vitro. Studies have shown that garlic compounds can activate immune system factors, thereby damaging the parasite structure or its eggs. CONCLUSION: Given the increase in using plants in the treatment of many diseases and the fact that plants can be a good alternative to chemical drugs in many cases, more comprehensive research is needed to introduce effective medicinal plants to treat diseases such as schistosomiasis.

A Systematic Review on Curcumin and Anti-Plasmodium berghei Effects.

BACKGROUND: Turmeric (Curcuma longa L.) is a popular spice containing curcumin that is responsible for its therapeutic effects. Curcumin with anti-inflammatory, antioxidant, anti-cancer, and antimicrobial activities has led to a lot of research focusing on it over the years. This systematic review aimed to evaluate research on the anti-Plasmodium berghei activity of curcumin and its derivatives. METHODS: Our study was performed according to PRISMA guidelines and was recorded in the database of a systematic review and preclinical meta-analysis of CAMARADESNC3Rs (SyRF). The search was performed in five databases, namely Scopus, PubMed, Web of Science, EMBASE, and Google Scholar, from 2010 to 2020. The following keywords were searched: "Plasmodium berghei", "Medicinal Plants", "Curcumin", "Concentration", Animals kind", "Treatment Durations", "Routes of Administration" and "in vivo". RESULTS: Of the 3,500 papers initially obtained, 14 articles were reliable and were thus scrutinized. Animal models were included in all studies. The most commonly used animal strain was Albino (43%), followed by C57BL/6 (22%). The other studies used various murine strains, including BALB/c (14%) and ICR (7%). Two (14%) studies did not mention the strain of animal model used. Curcumin alone or in combination with other compounds depending on the dose used, route of administration, and animal model showed a moderate to strong anti-Plasmodium berghei effect. CONCLUSION: According to the studies, curcumin has anti-malarial effects on Plasmodium berghei, and, however, its effect on human Plasmodium is unclear. Due to the side effects and drug resistance of current drugs in the treatment of human malaria, the use of new compounds with few or no side effects, such as curcumin, is recommended as an alternative or complementary treatment.

The use of minimal fluoroscopy for cardiac electrophysiology procedures: A meta-analysis and review of the literature.

BACKGROUND: Conventional catheter ablation involves prolonged exposure to ionizing radiation, potentially leading to detrimental health effects. Minimal fluoroscopy (MF) represents a safer alternative, which should be explored. Data on the safety and efficacy of this technique are limited. HYPOTHESIS: Our hypothesis is that MF is of equal efficacy and safety to conventional catheter ablation with the use of fluoroscopy by performing a meta-analysis of both randomized controlled trials (RCTs) and real-world registry studies. METHODS: Pubmed and Embase were searched from their inception to July 2020 for RCTs, cohort and observational studies that assessed the outcomes of catheter ablation using a MF technique versus the conventional approach. RESULTS: Fifteen studies involving 3795 patients were included in this meta-analysis. There was a significant reduction in fluoroscopy and procedural time with no difference in acute success (odds ratio [OR]:0.74, 95% CI: 0.50-1.10, p = .14), long-term success (OR:0.92, 95% CI: 0.65-1.31, p = .38), arrhythmia recurrence (OR:1.24, 95% CI: 0.75-2.06, p = .97) or rate of complications. (OR:0.83, 95% CI: 0.46-1.48, p = .65). Additionally sub-group analysis for those undergoing catheter ablation for atrial fibrillation (AF) did not demonstrate a difference in success or complication rates (OR:0.86, 95% CI: 0.30-2.42, p = .77). Multivariate meta-regression did not identify the presence of moderator variables. CONCLUSION: This updated meta-analysis demonstrated an overall reduction in procedural and fluoroscopy time for those undergoing a minimal fluoroscopic approach. There was no significant difference in either acute or chronic success rates or complications between a MF approach and conventional approach for the management of all arrhythmias including those undergoing catheter ablation for AF.

Did the COVID-19 Pandemic Spark a Public Interest in Pet Adoption?

This study aimed to determine if there has been an increase of global interest on pet adoption immediately after the WHO declaration of the pandemic and if the effect has been sustainable in 8 months on. We conducted a Google Trends search using keywords related to pet adoption. Relative search volume (RSV) was scored between 0 and 100 for the lowest and the highest, respectively. Top countries contributing to the dataset included Australia, the United States, Canada, New Zealand, the United Kingdom, Singapore, the Philippines, and Malaysia. From 2015 through 2020, the worldwide RSV for the categories of pet, dog and cat adoption peaked between April and May 2020, the early epidemic phase of the pandemic. These were significantly higher than the 5-year worldwide average RSV for all three categories (P = 0.001). Comparing to the same period in 2019, the RSV ratio (2020/2019) for both dog and cat adoption increased by up to 250%. Nonetheless, the RSV for dog adoption has been decreasing since July 2020 and returned to the 5-year average by December 2020. In contrast, the interest in cat adoption remained sustainably high, possibly reflecting the feline acclimation to indoor living. In conclusion, the global interest in pet adoptions surged in the early phase of the pandemic but not sustainable. With the launch of COVID-19 vaccines, there is a concern for separation anxiety and possible abandonment of these newly adopted pets when the owners would leave their homes for work in the future.

An Epidemiological Survey Regarding Ticks and Tick-Borne Diseases among Livestock Owners in Punjab, Pakistan: A One Health Context.

Recent global changes have led to an increase in the spread of ticks and tick-borne diseases (TBDs) affecting domestic ruminants and humans, with an annual loss of US $13.9-$18.7 billion. The current study determined the perception and practices of livestock farmers regarding tick infestation. A total of 112 livestock farms were surveyed in Punjab, Pakistan, among which animals from 42 (37.5%) farms were infested with ticks. Only 28.6% (n = 32) of the dairy farmers were consulting veterinarians for ticks control, while 86.7% (n = 97) of the respondents did not consider biosecurity measures in the control of tick transmission. Most of the respondents, 71.4% (n = 80), did not consider manual tick removal from their animals (i.e., by hand, followed by physically crushing) as a risky practice for spreading zoonotic diseases. Improper disposal of bottles of acaricides in the farm drainage was also observed, putting the environment and aquatic life at risk. These wrong practices may contribute to high disease burdens and economic losses, increasing the possibility of transmission of zoonotic TBDs and pollution of the environment. Therefore, an integrated One Health approach is required for the control of TBDs through environmentally friendly approaches.

The pests of a pest: A systematic review of ectoparasitic fauna among synanthropic rodents in the 21st century with meta-analysis.

Synanthropic rodents are important urban pests that frequently carry hematophagous ectoparasites. These blood-sucking pests are capable of transmitting epizootic and zoonotic pathogens by landing on one host after feeding on an infected animal. This study aimed to estimate the prevalence of ectoparasites carried by synanthropic rodents and discuss the pathogens that are associated with these external parasites. We searched relevant literatures using predefined criteria in the following databases: EMBASE, PUBMED, Web of Science and Scopus from January 2000 to June 2020. Quality of studies was evaluated using Newcastle-Ottawa scale (NOS). Of 35 included studies from 15 countries in Africa, America, Asia, Europe and Oceania, black rats (R. rattus), brown rats (R. norvegicus), pacific rats (R. exulans) and house mice (Mus musculus) were common synanthropic rodents. Mites (Mesostigmata, Sarcoptiformes and Trombidiformes) were the most prevalent (42.6%, 95% CI 26-59.2), followed by ticks (Ixodida) (21.5%, 95% CI 10.5-32.6), lice (Phthiraptera) (17.8%, 95% CI 7.7-27.9) and fleas (Siphonaptera) (14.1%, 95% CI 10.1-18.1). Heterogeneity (I2>96%) across studies was statistically significant. The ectoparasitic fauna was shared considerably by different urban rodent species and appeared to be more diverse in R. rattus and R. norvegicus. Nonetheless, pathogens carried by these ectoparasites were rarely investigated. In conclusion, ectoparasites are ubiquitous in urban-dwelling rodents but our understanding of the epidemiology and the associated pathogens of these parasites remains limited. Further studies are warranted to unravel the pathogen landscape found in rodent-associated ectoparasites.

Economic and Social Impacts of COVID-19 on Animal Welfare and Dairy Husbandry in Central Punjab, Pakistan.

Studies on the impact of the COVID-19 pandemic on animal welfare and dairy husbandry in low-income countries are limited. We conducted a survey between February and June 2020 to evaluate the economic impact and animal health problems upon the pandemic. Participants were lead veterinarians from 14 dairy farms with herd size between 100 and 500 in Lahore. These farms were major suppliers of milk and dairy products to central Punjab, Pakistan. During the pandemic, 10 of the 14 dairy farms relied on feed mill concentrates to provide feeds to their herds. Half of the farms reported feed shortage due to lockdowns. Six (43%) dairy farms have witnessed a 7.5% shortage of dry feed intake. In seven (50%) farms, the body condition score decreased by 0.24 point. The body score reduction was significantly associated with depleted feed intake (P = 0.005). The veterinarians of 10 (71%) farms failed to gain access to essential veterinary medications, hampering the treatment of sick animals. Due to feed shortage and drug unavailability, daily milk production reduced by two litters per cow in the herd of five (35%) farms. The reduced feed intake was significantly associated with the decrease in milk production (P = 0.003), while numerous downstream milk-processing facilities were out of service during the pandemic, significantly reducing the profit of six (43%) dairy farms. Finally, our study showed that the dairy farming industry and animal welfare were critically affected by three aspects: feed shortage, inaccessibility to essential veterinary drugs, and a reduced consumer demand for dairy products.

Parasitic Mite Fauna in Asian Poultry Farming Systems.

The ubiquitous presence of hematophagous avian mites threatens the poultry industry in Asia and worldwide, adversely affecting the quality and quantity of eggs and poultry meat produced by affected flocks. This leads to considerable economic loss and welfare-related issues. The role of these blood-feeding arthropods as disease vectors is increasingly recognized as they may carry important zoonotic and epizootic pathogens. The poultry mites, Dermanyssus gallinae (Poultry Red Mite-PRM), Ornithonysus sylviarum (Northern Fowl Mite-NFM), and Ornithonyssus bursa (Tropical Fowl Mite-TFM) are endemic species across the Asian continent. In less frequency, scaly leg mite, depluming mite, and fowl cyst mite were documented. Considering global climate change and the popularity of backyard farming, the incidence of avian mite infestation is expected to increase as Asian production expands. The TFM may start to colonize sub-tropical nations where the seasonal temperature is comparable to tropical regions. Pyrethroids, organophosphates, carbamates, and macrocyclic lactones are licensed acaricides for use in China, Japan, and India. In recent years, the development of acaricide resistance has compromised the efficacy of chemical control measures. Several botanical acaricides based on plant and fungal constituents are being investigated. Judicious integration of multiple approaches to manage poultry mite infestation is advised. In this article, we review the prevalence, geographical distribution, zoonotic potential, and control measures of avian mites in poultry farms in Asia.

Association of NPAC score with survival after acute myocardial infarction.

BACKGROUND AND AIMS: Risk stratification in acute myocardial infarction (AMI) is important for guiding clinical management. Current risk scores are mostly derived from clinical trials with stringent patient selection. We aimed to establish and evaluate a composite scoring system to improve short-term mortality classification after index episodes of AMI, independent of electrocardiography (ECG) pattern, in a large real-world cohort. METHODS: Using electronic health records, patients admitted to our regional teaching hospital (derivation cohort, n = 1747) and an independent tertiary care center (validation cohort, n = 1276), with index acute myocardial infarction between January 2013 and December 2017, as confirmed by principal diagnosis and laboratory findings, were identified retrospectively. RESULTS: Univariate logistic regression was used as the primary model to identify potential contributors to mortality. Stepwise forward likelihood ratio logistic regression revealed that neutrophil-to-lymphocyte ratio, peripheral vascular disease, age, and serum creatinine (NPAC) were significant for 90-day mortality (Hosmer- Lemeshow test, p = 0.21). Each component of the NPAC score was weighted by beta-coefficients in multivariate analysis. The C-statistic of the NPAC score was 0.75, which was higher than the conventional Charlson's score (C-statistic = 0.63). Judicious application of a deep learning model to our dataset improved the accuracy of classification with a C-statistic of 0.81. CONCLUSIONS: The NPAC score comprises four items from routine laboratory parameters to basic clinical information and can facilitate early identification of cases at risk of short-term mortality following index myocardial infarction. Deep learning model can serve as a gatekeeper to facilitate clinical decision-making.

Cathelicidin preserves intestinal barrier function in polymicrobial sepsis.

OBJECTIVES: The intestinal epithelium compartmentalizes the sterile bloodstream and the commensal bacteria in the gut. Accumulating evidence suggests that this barrier is impaired in sepsis, aggravating systemic inflammation. Previous studies reported that cathelicidin is differentially expressed in various tissues in sepsis. However, its role in sepsis-induced intestinal barrier dysfunction has not been investigated. DESIGN: To examine the role of cathelicidin in polymicrobial sepsis, cathelicidin wild-(Cnlp+/+) and knockout (Cnlp-/-) mice underwent cecal-ligation and puncture (CLP) followed by the assessment of septic mortality and morbidity as well as histological, biochemical, immunological, and transcriptomic analyses in the ileal tissues. We also evaluated the prophylactic and therapeutic efficacies of vitamin D3 (an inducer of endogenous cathelicidin) in the CLP-induced murine polymicrobial sepsis model. RESULTS: The ileal expression of cathelicidin was increased by three-fold after CLP, peaking at 4 h. Knockout of Cnlp significantly increased 7-day mortality and was associated with a higher murine sepsis score. Alcian-blue staining revealed a reduced number of mucin-positive goblet cells, accompanied by reduced mucin expression. Increased number of apoptotic cells and cleavage of caspase-3 were observed. Cnlp deletion increased intestinal permeability to 4kD fluorescein-labeled dextran and reduced the expression of tight junction proteins claudin-1 and occludin. Notably, circulating bacterial DNA load increased more than two-fold. Transcriptome analysis revealed upregulation of cytokine/inflammatory pathway. Depletion of Cnlp induced more M1 macrophages and neutrophils compared with the wild-type mice after CLP. Mice pre-treated with cholecalciferol (an inactive form of vitamin D3) or treated with 1alpha, 25-dihydroxyvitamin D3 (an active form of VD3) had decreased 7-day mortality and significantly less severe symptoms. Intriguingly, the administration of cholecalciferol after CLP led to worsened 7-day mortality and the associated symptoms. CONCLUSIONS: Endogenous cathelicidin promotes intestinal barrier integrity accompanied by modulating the infiltration of neutrophils and macrophages in polymicrobial sepsis. Our data suggested that 1alpha, 25-dihydroxyvitamin D3 but not cholecalciferol is a potential therapeutic agent for treating sepsis.

Systematic review of human gut resistome studies revealed variable definitions and approaches.

In this review, we highlight the variations of gut resistome studies, which may preclude comparisons and translational interpretations. Of 22 included studies, a range of 12 to 2000 antibiotic resistance (AR) genes were profiled. Overall, studies defined a healthy gut resistome as subjects who had not taken antibiotics in the last three to 12 months prior to sampling. In studies with de novo assembly, AR genes were identified based on variable nucleotide or amino acid sequence similarities. Different marker genes were used for defining resistance to a given antibiotic class. Validation of phenotypic resistance in the laboratory is frequently lacking. Cryptic resistance, collateral sensitivity and the interaction with repressors or promotors were not investigated. International consensus is needed for selecting marker genes to define resistance to a given antibiotic class in addition to uniformity in phenotypic validation and bioinformatics pipelines.

Regional differences in temporal incidence of Clostridium difficile infection: a systematic review and meta-analysis.

BACKGROUND: Previous decades have witnessed a change in the epidemiology of Clostridium difficile infections. This study aimed to determine temporal trends in the incidence of C difficile infection across geographic regions. METHODS: An initial search of the relevant literature was conducted from date inception to October 2018 without language restriction. We estimated the pooled incidences using logit transformation, weighted by inverse variance. The Joinpoint Regression Analysis Program was used to explore its temporal trend. RESULTS: Globally, the estimated incidence of C difficile infection increased from 6.60 per 10,000 patient-days in 1997 to 13.8 per 10,000 patient-days in 2004. Thereafter, a significant downward trend was observed, at -8.75% annually until 2015. From 2005 to 2015, the incidences in most European countries decreased at a rate between 1.97% and 4.11% per annum, except in France, where an increasing incidence was observed (ß = 0.16; P < .001). The incidences have stabilized in North America over the same period; however, in Asia, the incidence increased significantly from 2006 to 2014 (annualized percentage change = 14.4%; P < .001). The increase was greatest in Western Asian countries, including Turkey and Israel (ß > 0.10; P < .004). CONCLUSIONS: This study revealed rapid changes in the incidence of C difficile infection. This meta-analysis should inform the allocation of resources for controlling C difficile infection and future surveillance efforts in countries where epidemiologic information on C difficile infection remains sparse.

Everyday life experiences and mental health among conflict-affected forced migrants: A meta-analysis.

BACKGROUND: There are a growing number of forced migrants worldwide. Early detection of poor adjustment and interventions to facilitate positive adaptation within these communities is a critical global public health priority. A growing literature points to challenges within the post-migration context as key determents of poor mental health. AIMS: The current meta-analysis evaluated the association between daily stressors and poor mental health among these populations. METHOD: A systematic search in PsycINFO, PubMed, and Web of Science identified relevant studies from inception until the end of 2018. Effect sizes (correlation coefficients) were pooled using Fisher's Z transformation and reported with 95% confidence intervals. Moderator and mediator analyses were conducted. The protocol is available in PROSPERO [CRD42018081207]. RESULTS: Analysis of 59 eligible studies (n = 17,763) revealed that daily stressors were associated with higher psychiatric symptoms (Zr=0.126-0.199, 95% CI=0.084-0.168, 0.151-0.247, p<0.001) and general distress (Zr=0.542, 95% CI=0.332-0.752, p<0.001). Stronger effect sizes were observed for mixed daily stressors relative to subjective, interpersonal, and material daily stressors, and for general distress relative to posttraumatic stress symptoms and general well-being. Effect sizes were also stronger for children and adolescents relative to adults. Daily stressors fully mediated the associations of prior trauma with post-migration anxiety, depressive, and post-traumatic stress disorder symptoms. CONCLUSIONS: This meta-analysis provides a synthesis of existing research on the role of unfavorable everyday life experiences and their associations with poor mental health among conflict-affected forced migrants. Routine assessment and intervention to reduce daily stressors can prevent and reduce psychiatric morbidity in these populations.

Comparative cardiovascular risk in users versus non-users of xanthine oxidase inhibitors and febuxostat versus allopurinol users.

OBJECTIVES: The aim of this study is to determine major adverse cardiovascular events (MACE) and all-cause mortality comparing between xanthine oxidase inhibitors (XOIs) and non-XOI users, and between allopurinol and febuxostat. METHODS: This is a retrospective cohort study of gout patients prescribed anti-hyperuricemic medications between 2013 and 2017 using a territory-wide administrative database. XOI users were matched 1:1 to XOI non-users using propensity scores. Febuxostat users were matched 1:3 to allopurinol users. Subgroup analyses were conducted based on colchicine use. RESULTS: Of the 13 997 eligible participants, 3607 (25.8%) were XOI users and 10 390 (74.2%) were XOI non-users. After propensity score matching, compared with non-users (n = 3607), XOI users (n = 3607) showed similar incidence of MACE (hazard ratio [HR]: 0.997, 95% CI, 0.879, 1.131; P>0.05) and all-cause mortality (HR = 0.972, 95% CI 0.886, 1.065, P=0.539). Febuxostat (n = 276) users showed a similar risk of MACE compared with allopurinol users (n = 828; HR: 0.672, 95% CI, 0.416, 1.085; P=0.104) with a tendency towards a lower risk of heart failure-related hospitalizations (HR = 0.529, 95% CI 0.272, 1.029; P=0.061). Concurrent colchicine use reduced the risk for all-cause mortality amongst XOI users (HR = 0.671, 95% 0.586, 0.768; P<0.001). CONCLUSION: In gout patients, XOI users showed similar risk of MACE and all-cause mortality compared with non-users. Compared with allopurinol users, febuxostat users showed similar MACE and all-cause mortality risks but lower heart failure-related hospitalizations.

Antibiotic-Resistant Community-Acquired Bacterial Pneumonia.

Antimicrobial resistance is a global concern, and prudent use of antibiotics is essential to preserve the current armamentarium of effective drugs. Acute respiratory tract infection is the most common reason for antibiotic prescription in adults. In particular, community-acquired pneumonia poses a significant health challenge and economic burden globally, especially in the current landscape of a dense and aging population. By updating the knowledge on the common antimicrobial-resistant pathogens in community-acquired respiratory tract infections, their prevalence, and resistance may pave the way to enhancing appropriate antibiotic use in the ambulatory and health care setting.

Anaesthesia use in catheter ablation for atrial fibrillation: a systematic review and meta-analysis of observational studies.

OBJECTIVES: This meta-analysis and systematic review seeks to compare both characteristic parameters and procedural outcomes of atrial fibrillation (AF) catheter ablation in patients under general anaesthesia (GA)/deep sedation and mild/moderate sedation. BACKGROUND: Catheter ablation has become a widely applied intervention for treating symptomatic AF and arrhythmias that are refractory to medical therapy. It can be conducted through from mild sedation to GA. METHODS: PubMed and Embase were searched up to July 2018 for randomised controlled trials, cohort and observational studies that assessed the outcomes of catheter ablation under GA/deep sedation or mild/moderate sedation. Nine studies were included in this meta-analysis after screening with the inclusion and exclusion criteria. Heterogeneity between studies and publication bias was evaluated by I2 index and Egger's regression, respectively. RESULTS: Our meta-analysis found catheter AF ablation with GA/deep sedation to be associated with reduced risk of recurrence (RR: 0.79, 95% CI 0.56 to 1.13, p=0.20) and complications (RR: 0.95, 95% CI 0.64 to 1.42, p=0.82), though statistically insignificant. In terms of procedural parameters, there was no significant difference between the two groups for both procedural time (SMD: -0.13, 95% CI -0.90 to 0.63, p=0.74) and fluoroscopy time (SMD: -0.41, 95% CI -1.40 to 0.58, p=0.41). Univariate meta-regression did not reveal any covariates as a moderating factor for complication and recurrence risk. CONCLUSION: Apart from an increased likelihood of procedural success, ablation by GA/deep sedation was found to be non-significantly different from the mild/moderate sedation approach in both procedural parameters and outcome measures.

Percutaneous Coronary Intervention Versus Medical Therapy for Chronic Total Occlusion of Coronary Arteries: A Systematic Review and Meta-Analysis.

PURPOSE OF REVIEW: Chronic total occlusion (CTO) of the coronary arteries is a significant clinical problem and has traditionally been treated by medical therapy or coronary artery bypass grafting. Recent studies have examined percutaneous coronary intervention (PCI) as an alternative option. RECENT FINDINGS: This systematic review and meta-analysis compared medical therapy to PCI for treating CTOs. PubMed and Embase were searched from their inception to March 2019 for studies that compared medical therapy and PCI for clinical outcomes in patients with CTOs. Quality of the included studies was assessed by Newcastle-Ottawa scale. The results were pooled by DerSimonian and Laird random- or fixed-effect models as appropriate. Heterogeneity between studies and publication bias was evaluated by I2 index and Egger's regression, respectively. Of the 703 entries screened, 17 studies were included in the final analysis. This comprised 11,493 participants. Compared to PCI, medical therapy including randomized and observational studies was significantly associated with higher risk of all-cause mortality (risk ratio (RR) 1.99, 95% CI 1.38-2.86), cardiac mortality (RR 2.36 (1.97-2.84)), and major adverse cardiac event (RR 1.25 (1.03-1.51)). However, no difference in the rate of myocardial infarction and repeat revascularization procedures was observed between the two groups. Univariate meta-regression demonstrated multiple covariates as independent moderating factors for myocardial infarction and repeat revascularization but not cardiac death and all-cause mortality. However, when only randomized studies were included, there was no difference in overall mortality or cardiac death. In CTO, when considering randomized and observational studies, medical therapy might be associated with a higher risk of mortality and myocardial infarction compared to PCI treatment.

Preclinical evidence of sphingosine kinase 1 inhibition in alleviation of intestinal epithelial injury in polymicrobial sepsis.

BACKGROUND: Intestinal epithelial injury in septic patients predicts subsequent development of multiple organ failure, but its regulation by host factors remains unclear. Sphingosine kinase 1 is an enzyme-regulating inflammatory response. METHODS: Cecal ligation and puncture was used to induce sepsis in C57BL/6 mice with and without N,N-dimethylsphingosine, a SphK1 inhibitor. Symptom severity was monitored by murine sepsis severity score. The intestinal barrier function was determined using 4KDa fluorescein-dextran. Bacterial load in the bloodstream was determined by 16S rRNA gene amplification. RESULTS AND CONCLUSIONS: Our preliminary experimental data showed that expression of sphingosine kinase 1 in ileum was increased by sixfold in septic mice. Pharmacological blockade of sphingosine kinase 1 alleviated septic symptoms. The intestinal permeability and bacterial load in the bloodstream were also reduced in these animals. We hypothesized that inhibition of sphingosine kinase 1 may reduce pro-inflammatory cytokine production, and alleviate intestinal epithelial injury during sepsis. Further mechanistic studies and clinical specimen analyses are warranted.

Local infiltration with cocktail analgesics during 2 level lumbar spinal fusion surgery: Study protocol of a randomized controlled trial.

BACKGROUND: Despite introducing novel analgesics, pain management for spine surgery remains a challenge. Multimodal pain control has recently gained popularity in surgical spine care. We proposed a novel management approach using multimodal cocktail analgesics. Injection to skin surrounding surgical incision site will be given perioperatively. This study evaluates the safety and efficacy of cocktail analgesic injection on pain management following lumbar spinal fusion surgery. METHODS: Thirty-six patients with degenerative lumbar spinal diseases on the waiting list for lumbar spinal fusion surgery will be recruited. Patients will be randomly assigned to receive either cocktail analgesic injection or sterile saline before surgical wound closure. All patients will routinely receive postoperative intravenous patient-controlled analgesia (IV-PCA) with sufentanil on an as-needed basis without a basal dose. The primary outcome is perceived pain intensity as measured by visual analog pain score. Secondary outcomes include sufentanil consumption, time to first use of IV-PCA, rescue analgesics consumption, and the presence of adverse effects. Findings of this interventional trial will provide novel evidence supporting the superior effect of cocktail analgesic injection during surgery. TRIAL REGISTRATION NUMBER: ChiCTR-IPR-17013094.