Background: Diabetes is a risk factor for postoperative complications. Previous meta-analyses have shown that elevated glycated hemoglobin (HbA1c) levels are associated with postoperative complications in various surgical populations. However, this is the first meta-analysis to investigate the association between preoperative HbA1c levels and postoperative complications in patients undergoing elective major abdominal surgery. Methods: PRISMA guidelines were adhered to for this study. Six databases were searched up to April 1, 2020. Primary studies investigating the effect of HbA1c levels on postoperative complications after elective major abdominal surgery were included. Risk of bias and quality of evidence assessments were performed. Data were pooled using a random effects model. Meta-regression was performed to evaluate different HbA1c cut-off values. Results: Twelve observational studies (25,036 patients) were included. Most studies received a ‘good’ and ‘moderate quality’ score using the NOS and GRADE, respectively. Patients with a high HbA1c had a greater risk of anastomotic leaks (odds ratio [OR]: 2.80, 95% CI [1.63, 4.83], P < 0.001), wound infections (OR: 1.21, 95% CI [1.08, 1.36], P = 0.001), major complications defined as Clavien-Dindo [CD] 3–5 (OR: 2.16, 95% CI [1.54, 3.01], P < 0.001), and overall complications defined as CD 1–5 (OR: 2.12, 95% CI [1.48, 3.04], P < 0.001). Conclusions An HbA1c between 6% and 7% is associated with higher risks of anastomotic leaks, wound infections, major complications, and overall postoperative complications. Therefore, guidelines with an HbA1c threshold > 7% may be putting pre-optimized patients at risk. Future randomized controlled trials are needed to explore causation before policy changes are made.

Hippo signaling pathways are evolutionarily conserved signal transduction mechanisms mainly involved in organ size control, tissue regeneration, and tumor suppression. However, in mammals, the primary role of Hippo signaling seems to be regulation of immunity. As such, humans with null mutations in STK4 (mammalian homologue of Drosophila Hippo; also known as MST1) suffer from recurrent infections and autoimmune symptoms. Although dysregulated T cell homeostasis and functions have been identified in MST1-deficient human patients and mouse models, detailed cellular and molecular bases of the immune dysfunction remain to be elucidated. Although the canonical Hippo signaling pathway involves transcriptional coactivator Yes-associated protein (YAP) or transcriptional coactivator with PDZ motif (TAZ), the major Hippo downstream signaling pathways in T cells are YAP/TAZ-independent and they widely differ between T cell subsets. Here we will review Hippo signaling mechanisms in T cell immunity and describe their implications for immune defects found in MST1-deficient patients and animals. Further, we propose that mutual inhibition of Mst and Akt kinases and their opposing roles on the stability and function of forkhead box O and β-catenin may explain various immune defects discovered in mutant mice lacking Hippo signaling components. Understanding these diverse Hippo signaling pathways and their interplay with other evolutionarily-conserved signaling components in T cells may uncover molecular targets relevant to vaccination, autoimmune diseases, and cancer immunotherapies.

INTRODUCTION: A second-tier rapid response team (RRT) is activated for patients who do not respond to first-tier measures. The premise of a tiered response is that first-tier responses by a ward team may identify and correct early states of deterioration or establish goals of care, thereby reducing unnecessary escalation of care to the RRT. Currently, utilisation and outcomes of tiered RRTs remain poorly described. METHODS: A prospective observational study of adult patients (age ≥18 years) who required RRT activations was conducted from February 2018 to December 2019. RESULTS: There were 951 consecutive RRT activations from 869 patients and 76.0% patients had a National Early Warning Score (NEWS) ≥5 at the time of RRT activation. The majority (79.8%) of patients required RRT interventions that included endotracheal intubation (12.7%), point-of-care ultrasound (17.0%), discussing goals of care (14.7%) and intensive care unit (ICU) admission (24.2%). Approximately 1 in 3 (36.6%) patients died during hospitalisation or within 30 days of RRT activation. In multivariate analysis, age ≥65 years, NEWS ≥7, ICU admission, longer hospitalisation days at RRT activation, Eastern Cooperative Oncology Group performance scores ≥3 (OR [odds ratio] 2.24, 95% CI [confidence interval] 1.45-3.46), metastatic cancer (OR 2.64, 95% CI 1.71-4.08) and haematological cancer (OR 2.78, 95% CI 1.84-4.19) were independently associated with mortality. CONCLUSION Critical care interventions and escalation of care are common with second-tier RRTs. This supports the need for dedicated teams with specialised critical care services. Poor functional status, metastatic and haematological cancer are significantly associated with mortality, independent of age, NEWS and ICU admission. These factors should be considered during triage and goals of care discussion.
Adolescent ; Adult ; Aged ; Critical Care ; Hospital Mortality ; Hospital Rapid Response Team ; Humans ; Prospective Studies ; Tertiary Care Centers

OBJECTIVETo investigate and analyze the characteristics of Meridian Sinew (Jingjin) syndrome in patients with whiplash-associated disorders (WAD).

METHODSFrom August 2010 to September 2011, 313 WAD cases from New York and California states were collected. The survey mostly collects the information of "Sinew Knotted Points" and symptoms of four types of Meridian Sinew differentiation-Taiyang, Shaoyin, Shaoyang and Yangming.

RESULTSAmong the cases which are on the average of medium injury level, the higher frequency of "Sinew Knotted Points" tenderness were found on Jianwaishu (SI 14), Jianzhongshu (SI 15), Tianchuang (SI 16), C3-6 Spinous Process, Dazhui (GV 14), Fengchi (GB 20), Tianliao (SJ 15) and Tianding (LI 17). The most commonly presented symptoms were widespread spasm and tenderness in the neck (Taiyang), difficulty in lateral flexion (Shaoyang), problems of extension and flexion (Taiyang), and stiffness and pain during neck movement (Yangming). Among the cases, 237 cases (75.72%) were related to Taiyang Meridian Sinew syndrome, 82 cases (26.20%) to Shaoyin syndrome and 175 (55.91%) and 176 (56.23%) cases to Shaoyang and Yangming syndrome respectively. The most of cases presented in a combination format. The syndrome distribution under Grade I, II and III reflected that more combination of the Meridian Sinew syndromes in the whiplash injury patients which is resulted from more severity of injury.

CONCLUSIONIt is practical to identify the location of abnormality through Meridian Sinew differentiation, considering both "Sinew Knotted Points" tenderness and corresponding symptoms, for the local neck symptoms of WAD.

Adult ; Female ; Humans ; Male ; Meridians ; Syndrome ; Whiplash Injuries ; therapy

Using directed mutagenesis and phage display on a soluble fragment of the human immunoglobulin super-family receptor ILT2 (synonyms: LIR1, MIR7, CD85j), we have selected a range of mutants with binding affinities enhanced by up to 168,000-fold towards the conserved region of major histocompatibility complex (MHC) class I molecules. Produced in a dimeric form, either by chemical cross-linking with bivalent polyethylene glycol (PEG) derivatives or as a genetic fusion with human IgG Fc-fragment, the mutants exhibited a further increase in ligand-binding strength due to the avidity effect, with resident half-times (t(1/2)) on the surface of MHC I-positive cells of many hours. The novel compounds antagonized the interaction of CD8 co-receptor with MHC I in vitro without affecting the peptide-specific binding of T-cell receptors (TCRs). In both cytokine-release assays and cell-killing experiments the engineered receptors inhibited the activation of CD8(+) cytotoxic T lymphocytes (CTLs) in the presence of their target cells, with subnanomolar potency and in a dose-dependent manner. As a selective inhibitor of CD8(+) CTL responses, the engineered high affinity ILT2 receptor presents a new tool for studying the activation mechanism of different subsets of CTLs and could have potential for the development of novel autoimmunity therapies.
Amino Acid Sequence ; Antigens, CD ; chemistry ; genetics ; pharmacology ; Autoimmunity ; Biological Assay ; Cell Line ; Cytotoxicity, Immunologic ; genetics ; immunology ; Dose-Response Relationship, Immunologic ; Humans ; Immunoglobulins ; immunology ; metabolism ; Immunologic Factors ; chemistry ; genetics ; pharmacology ; Kinetics ; Leukocyte Immunoglobulin-like Receptor B1 ; Lymphocyte Activation ; genetics ; immunology ; Major Histocompatibility Complex ; genetics ; immunology ; Molecular Sequence Data ; Molecular Targeted Therapy ; Mutagenesis, Site-Directed ; Peptide Library ; Polyethylene Glycols ; Protein Binding ; genetics ; immunology ; Receptors, Immunologic ; chemistry ; genetics ; Recombinant Fusion Proteins ; genetics ; metabolism ; T-Lymphocytes, Cytotoxic ; immunology ; metabolism

Objective:To explore the methodology of the evidence-based expert consensus formulation process of traditional Chinese medicine(TCM)nursing taking stroke as an example.Methods:First,preliminary and comprehensive presentation of all stroke-related symptoms and corre-sponding TCM nursing techniques involved were revealed through bibliometric analysis.Then,selection of stroke symptoms and TCM nursing techniques for inclusion in the consensus was performed using an expert consultation method.Next,we determined the search strategy for a precise evidence search;conducted an evaluation of evidence quality and the grade of the evidence;and completed evidence extraction,evidence analysis,and evidence synthesis based on the included symptoms and TCM nursing techniques.The Delphi method was then applied to determine the strength of each recommendation and the choice of nursing care points by referring to the Grading of Recommendations,Assessment,Devel-opment,and Evaluations grid.Finally,we conducted an external expert validation of the Delphi results to form an expert consensus guideline.Results:Through the bibliometric analysis,22 stroke symptoms and 18 TCM nursing techniques were identified in the literature.Then,after expert consultation,22 symptoms and 111 pairs of symptoms combined with TCM nursing techniques were selected for the evidence search.Evidence integration yielded 10 stroke symptoms corresponding to 29 bodies of evidence;these 10 symptoms were retained through the Delphi consultation,and recommendation strength results for 26 recommendations were obtained.A total of 9 symptoms were further retained for expert external validation to form 24 rec-ommendations,with a recommendation process score range of 7.64-9.99 points and a more scientific and standardized recommendation-formation process.Conclusion:Owing to the current limited conditions of evidence-based resources for TCM nursing,the present consensus-building process represents only a preliminary exploration of an evidence-based expert consensus for TCM nursing to provide a reference for a more scientific and standardized methodology.

Humans ; Hospital Rapid Response Team ; Attitude of Health Personnel ; Perception