Multidisciplinary Teams for the Management of Infective Endocarditis: A Systematic Review and Meta-analysis.

Background: The management of infective endocarditis (IE) is complex owing to a high burden of morbidity and mortality. Recent guidelines recommend dedicated multidisciplinary teams (MDTs) for the management of IE. The aim of this systematic review and meta-analysis was to evaluate and summarize the effect of MDT management on patient outcomes. Methods: A systematic review was performed and, where feasible, results were meta-analyzed; otherwise, results were summarized narratively. Data extraction and quality assessment were performed in duplicate. Restricted maximum likelihood random effects models were used to calculate unadjusted risk ratios and 95% CIs. Results: Screening of 2343 studies based on title and abstract yielded 60 full-text reviews; 18 studies were summarized narratively, of which 15 were included in a meta-analysis of short-term mortality. Meta-analysis resulted in a risk ratio of 0.61 (95% CI, .47-.78; I2 = 62%) for mortality in favor of a dedicated MDT as compared with usual care. Length of stay was variable, with 55% (10/18) of studies reporting an increased length of stay. Most studies (16/18, 88.9%) reported a decreased time to surgery and an increased rate of surgery (13/18, 73%). No studies reported on patient-reported outcomes. Conclusions: This is the first systematic review and meta-analysis to assess the impact of MDT management on IE. The sum of evidence demonstrated a significant association between MDTs and improved short-term mortality. Further research is needed to evaluate benefits of virtual MDT care, cost-effectiveness, and the impact on patient-reported outcomes and long-term mortality.

Guidelines for Diagnosis and Management of Infective Endocarditis in Adults: A WikiGuidelines Group Consensus Statement.

Importance: Practice guidelines often provide recommendations in which the strength of the recommendation is dissociated from the quality of the evidence. Objective: To create a clinical guideline for the diagnosis and management of adult bacterial infective endocarditis (IE) that addresses the gap between the evidence and recommendation strength. Evidence Review: This consensus statement and systematic review applied an approach previously established by the WikiGuidelines Group to construct collaborative clinical guidelines. In April 2022 a call to new and existing members was released electronically (social media and email) for the next WikiGuidelines topic, and subsequently, topics and questions related to the diagnosis and management of adult bacterial IE were crowdsourced and prioritized by vote. For each topic, PubMed literature searches were conducted including all years and languages. Evidence was reported according to the WikiGuidelines charter: clear recommendations were established only when reproducible, prospective, controlled studies provided hypothesis-confirming evidence. In the absence of such data, clinical reviews were crafted discussing the risks and benefits of different approaches. Findings: A total of 51 members from 10 countries reviewed 587 articles and submitted information relevant to 4 sections: establishing the diagnosis of IE (9 questions); multidisciplinary IE teams (1 question); prophylaxis (2 questions); and treatment (5 questions). Of 17 unique questions, a clear recommendation could only be provided for 1 question: 3 randomized clinical trials have established that oral transitional therapy is at least as effective as intravenous (IV)-only therapy for the treatment of IE. Clinical reviews were generated for the remaining questions. Conclusions and Relevance: In this consensus statement that applied the WikiGuideline method for clinical guideline development, oral transitional therapy was at least as effective as IV-only therapy for the treatment of IE. Several randomized clinical trials are underway to inform other areas of practice, and further research is needed.

The protective effect of L-Shikonin on LPS/D-GalN-induced acute liver injury in mice via inhibiting NF-κB inflammatory signaling pathway / 中国药理学通报

Aim To investigate the anti-inflammatory effect of L-Shikonin ( SK ) on lipopolysaccharide ( LPS)-induced RAW 264. 7 macrophages in vitro and its protective effect on LPS/D-GalN-induced acute liver injury. Methods The mouse model of acute liver in¬jury was established in vivo experiments by LPS/D- GalN. The survival rate of the mice and the changes of liver and spleen indices in each group were examined. The levels of AST, ALT and AKP in serum and NO, superoxide dismutase ( SOD ) and malondialdehyde (MDA) in liver tissue homogenate were measured, and the histopathological sections of the liver of each group were observed by H&E staining. M I T colorimet- ric assay was used for cell viability in vitro experi¬ments, Griess method for the detection of NO content, RT-PCR assay and Western blot assay for examining the effect of levulinic acid on the expression levels of mRNA and related pathway proteins of pro-inflammato¬ry factors in LPS-induced RAW264. 7 cells. Results The results of in vivo experiments showed that L-SK significantly improved the liver and spleen indices, de¬creased AST, ALT and AKP levels in serum, de¬creased NO and MDA in liver homogenate, and in¬creased SOD activity in mice with acute liver injury. The results of in vitro experiments showed that L-SK significantly inhibited the mRNA expression of INOS, COX2, I FN-(3 and pro-inflammatory factors 1L-6, TNF-a and IL-10 in LPS-induced RAW264. 7 cells, and significantly inhibited the protein expression of IN¬OS, COX2 and the NF-kB signaling pathway. Conclu¬sions L-SK has good anti-inflammatory effects in LPS-induced inflammation in RAW 264. 7 cells in vitro. Il inhibits the protein expression of phosphorylated P65 and IKKaαβ in the NF-kB signaling pathway, thereby suppressing the anti-inflammatory effects in vitro and L- Shikonin has protective effects against acute liver injury in mice.

Effects of extracts from Arnebia euchroma (Royle) Johnst on apoptosis of HepG2 and its anti-hepatocellular carcinoma in mice / 中国药理学通报

Aim To study the apoptosis of human hep-atoma cell line ( HepG2 ) induced by different polar parts of Arnebia euchroma ( Royle ) Johnst ( AE ) and to verify its anti-hepatoma effect by a mouse orthotopic liver cancer model so as to explore the anti-cancer effect of AE extract. Methods Firstly, MTT method and Annexin V-FITC/PI double staining method were used to detect the anti-proliferative and pro-apoptotic effects of each polar part of AE on HepG2 cells, and Western blot was used to detect the expression of Bcl-2 apoptosis family proteins incells. Based on the above experimental results, the effective parts with significant pro-apoptotic effect were screened out for anti-in situ liver cancer experiments in mice, and the organ indexes, liver function indexes and tissue sections of mice with orthotopic liver cancer before and after administration were evaluated. Results With the decrease of the polarity of AE extract,the anti-proliferation and pro-apoptotic effects on HepG2 cells were enhanced, and the anti-proliferation and apoptosis-inducing effects of AE petroleum ether fraction ( AEP) were the most significant. When AEP dose was 1.56 (μg • L

Determination of content of matricin extracted from Cichorium glandulosum Boiss et Huet with n-butanol and its protective effect on hepatic fibrosis in rats / 中国药理学通报

Aim To investigate the effects of Cichorium glandulosum N-butanol extraction site (C G E) on hepatic fibrosis (H F) in SD rats and to determine the content of the main effective component matricin. Methods HPLC method was used to determine the content of matricin in CGE. The SD rats were randomly divided into control group, model group, CGE low-dose groups, medium-dose and high-dose, and curcumin group. In addition to control group rats' back subcutaneous injection (s c) normal saline, rats in the other groups were treated with body weight sc 40 % CC1

Use of Novel Strategies to Develop Guidelines for Management of Pyogenic Osteomyelitis in Adults: A WikiGuidelines Group Consensus Statement.

Importance: Traditional approaches to practice guidelines frequently result in dissociation between strength of recommendation and quality of evidence. Objective: To construct a clinical guideline for pyogenic osteomyelitis management, with a new standard of evidence to resolve the gap between strength of recommendation and quality of evidence, through the use of a novel open access approach utilizing social media tools. Evidence Review: This consensus statement and systematic review study used a novel approach from the WikiGuidelines Group, an open access collaborative research project, to construct clinical guidelines for pyogenic osteomyelitis. In June 2021 and February 2022, authors recruited via social media conducted multiple PubMed literature searches, including all years and languages, regarding osteomyelitis management; criteria for article quality and inclusion were specified in the group's charter. The GRADE system for evaluating evidence was not used based on previously published concerns regarding the potential dissociation between strength of recommendation and quality of evidence. Instead, the charter required that clear recommendations be made only when reproducible, prospective, controlled studies provided hypothesis-confirming evidence. In the absence of such data, clinical reviews were drafted to discuss pros and cons of care choices. Both clear recommendations and clinical reviews were planned with the intention to be regularly updated as new data become available. Findings: Sixty-three participants with diverse expertise from 8 countries developed the group's charter and its first guideline on pyogenic osteomyelitis. These participants included both nonacademic and academic physicians and pharmacists specializing in general internal medicine or hospital medicine, infectious diseases, orthopedic surgery, pharmacology, and medical microbiology. Of the 7 questions addressed in the guideline, 2 clear recommendations were offered for the use of oral antibiotic therapy and the duration of therapy. In addition, 5 clinical reviews were authored addressing diagnosis, approaches to osteomyelitis underlying a pressure ulcer, timing for the administration of empirical therapy, specific antimicrobial options (including empirical regimens, use of antimicrobials targeting resistant pathogens, the role of bone penetration, and the use of rifampin as adjunctive therapy), and the role of biomarkers and imaging to assess responses to therapy. Conclusions and Relevance: The WikiGuidelines approach offers a novel methodology for clinical guideline development that precludes recommendations based on low-quality data or opinion. The primary limitation is the need for more rigorous clinical investigations, enabling additional clear recommendations for clinical questions currently unresolved by high-quality data.

Outcomes of COVID-19 Patients Hospitalized at Acute Care Services: Real-World Experience in the New York Metropolitan Area During the Early Pandemic Before Initiation of Clinical Trials.

As New York became the epicenter of the COVID-19 pandemic early on, clinicians were challenged to provide optimal medical and pharmaceutical care, despite the paucity of supporting literature and guidance. We sought to describe prescribing patterns and outcomes of physician response to the urgent need to treat COVID-19 patients before initiation of randomized clinical trials. METHODS: This was a retrospective cohort study of adult patients with COVID-19 initially admitted to acute care services during March 2020. Critically ill patients requiring intensive care unit level of care on admission were excluded. RESULTS: A total of 639 consecutive patients (supportive care, n = 247; treatment n = 392) were included in the analysis. Overall, the 28-day mortality rate was 12.2%. The mortality was 8.7% higher in the treatment group (15.6% vs 6.9% in the supportive care group, P < 0.001). Treatment was not protective against progression to severe disease (18.4% vs 3.6% with supportive care, P < 0.0001). Time to defervescence, duration of oxygen support, and hospital and intensive care unit (ICU) length of stay were also higher in the treatment group. In multivariate analysis, 60 years or older, presence of severe disease, and need for ICU admission were identified as independent predictors of 28-day mortality. There were 41 (10.5%) adverse event in the treatment group, with the majority being QT prolongation and gastrointestinal effects. CONCLUSIONS: In this cohort of hospitalized patients admitted to acute care services, treatment with hydroxychloroquine, lopinavir/ritonavir or both could not be shown to improve mortality, progression to severe disease, or clinical response.

Role of transient receptor potential melastatin 8 channels in migraine mechanism in rats / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the role of transient receptor potential melastatin 8 (TRPM8) channels in migraine mechanism in rats by measuring the changes in expression of TRPM8 in the trigeminal nerve of rats with migraine.</p><p><b>METHODS</b>Twenty male Sprague-Dawley rats were randomly and equally divided into a blank control group and a model group. Nitroglycerin (10 mg/kg) was injected subcutaneously in the back of the neck once a week for 5 weeks, to prepared a rat model of migraine without aura. Normal saline was injected subcutaneously instead of nitroglycerin in the control group. At 4 hours after the final injection, behavior scoring of all rats was performed, and then the trigeminal nerve ganglions of rats in both groups were collected for measurement of expression of N-methyl-D-aspartate receptor (NMDAR), protein kinase A (PKA), and TRPM8 using immunohistochemical staining, immunofluorescence, and Western blot, respectively.</p><p><b>RESULTS</b>The behavior score in each week during the rat model preparing was significantly higher in the model group than in the control group (P<0.05). The expression of NMDAR, PKA, and TRPM8 in the model group was significantly higher than in the control group (P<0.01). Both the behavior score and the expression of NMDAR were positively correlated with the expression of TRPM8 (r=0.822 and 0.794 respectively; P<0.01).</p><p><b>CONCLUSIONS</b>TRPM8 may be involved in migraine mechanism probably by activation of the NMDAR pathway.</p>