The Distribution Trend and Antimicrobial Susceptibility of Uropathogens in Taiwan: Retrospective Analysis of a 10-Year Study.

Background: The prevalence and antimicrobial susceptibility of uropathogens can vary with time and geographical location. Empirical antibiotic treatment is frequently started before the urine culture reports are received; thus, the correct selection of antibiotics is imperative, as inappropriate use could increase resistance rates. This study evaluates the distribution trends and antimicrobial susceptibility of common uropathogens in Taiwan to help predict causative pathogens, prevent overly broad antibiotic use, and guide the optimal prescription of empirical antibiotic therapy to improve prognosis. Methods: This retrospective study extracted 5,672,246 urine culture sample data, including outpatient, emergency, and inpatient departments, during 2007-2017 from the Chang Gung Research Database. We examined the trend and susceptibility of uropathogens. Results: The three leading microorganisms were Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumoniae), and Pseudomonas aeruginosa (P. aeruginosa). E. coli. was more common among females (42.7%) than males (24.7%), while P. aeruginosa was more common among males (10.2%) than females (4.42%). E. coli and K. pneumoniae were highly susceptible to carbapenems, followed by aminoglycosides. Nevertheless, an increased antimicrobial resistance trend was observed in cephalosporins and quinolones. Conclusions: This study establishes E. coli and K. pneumoniae as the predominant uropathogens. Age and gender of patients result in distribution variations of uropathogens, but geographical location does not. In addition, P. aeruginosa occurs more in the sample of elderly and that too among males. Overall, this study could help clinicians choose appropriate antibiotics to treat urinary tract infections per the prevalent uropathogens and local antimicrobial susceptibility patterns.

Using time-course as an essential factor to accurately predict sepsis-associated mortality among patients with suspected sepsis.

BACKGROUND: Biomarker dynamics in different time-courses might be the primary reason why a static measurement of a single biomarker cannot accurately predict sepsis outcomes. Therefore, we conducted this prospective hospital-based cohort study to simultaneously evaluate the performance of several conventional and novel biomarkers of sepsis in predicting sepsis-associated mortality on different days of illness among patients with suspected sepsis. METHODS: We evaluated the performance of 15 novel biomarkers including angiopoietin-2, pentraxin 3, sTREM-1, ICAM-1, VCAM-1, sCD14 and 163, E-selectin, P-selectin, TNF-alpha, interferon-gamma, CD64, IL-6, 8, and 10, along with few conventional markers for predicting sepsis-associated mortality. Patients were grouped into quartiles according to the number of days since symptom onset. Receiver operating characteristic curve (ROC) analysis was used to evaluate the biomarker performance. RESULTS: From 2014 to 2017, 1,483 patients were enrolled, of which 78% fulfilled the systemic inflammatory response syndrome criteria, 62% fulfilled the sepsis-3 criteria, 32% had septic shock, and 3.3% developed sepsis-associated mortality. IL-6, pentraxin 3, sCD163, and the blood gas profile demonstrated better performance in the early days of illness, both before and after adjusting for potential confounders (adjusted area under ROC curve [AUROC]:0.81-0.88). Notably, the Sequential Organ Failure Assessment (SOFA) score was relatively consistent throughout the course of illness (adjusted AUROC:0.70-0.91). CONCLUSION: IL-6, pentraxin 3, sCD163, and the blood gas profile showed excellent predictive accuracy in the early days of illness. The SOFA score was consistently predictive of sepsis-associated mortality throughout the course of illness, with an acceptable performance.

Comparison of the Diagnostic Accuracies of Monocyte Distribution Width, Procalcitonin, and C-Reactive Protein for Sepsis: A Systematic Review and Meta-Analysis.

OBJECTIVES: We performed a systemic review and meta-analysis to evaluate the diagnostic accuracy of monocyte distribution width (MDW) and to compare with procalcitonin and C-reactive protein (CRP), in adult patients with sepsis. DATA SOURCES: A systematic literature search was performed in PubMed, Embase, and the Cochrane Library to identify all relevant diagnostic accuracy studies published before October 1, 2022. STUDY SELECTION: Original articles reporting the diagnostic accuracy of MDW for sepsis detection with the Sepsis-2 or Sepsis-3 criteria were included. DATA EXTRACTION: Study data were abstracted by two independent reviewers using a standardized data extraction form. DATA SYNTHESIS: Eighteen studies were included in the meta-analysis. The pooled sensitivity and specificity of MDW were 84% (95% CI [79-88%]) and 68% (95% CI [60-75%]). The estimated diagnostic odds ratio and the area under the summary receiver operating characteristic curve (SROC) were 11.11 (95% CI [7.36-16.77]) and 0.85 (95% CI [0.81-0.89]). Significant heterogeneity was observed among the included studies. Eight studies compared the diagnostic accuracies of MDW and procalcitonin, and five studies compared the diagnostic accuracies of MDW and CRP. For MDW versus procalcitonin, the area under the SROC was similar (0.88, CI = 0.84-0.93 vs 0.82, CI = 0.76-0.88). For MDW versus CRP, the area under the SROC was similar (0.88, CI = 0.83-0.93 vs 0.86, CI = 0.78-0.95). CONCLUSIONS: The results of the meta-analysis indicate that MDW is a reliable diagnostic biomarker for sepsis as procalcitonin and CRP. Further studies investigating the combination of MDW and other biomarkers are advisable to increase the accuracy in sepsis detection.

When a Rapid Accurate Diagnosis Changes Therapeutic Approach: Recognizing Acute Abdominal Pain with Ascites as a Possible Presentation of Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a chronic, multi-organ autoimmune disease which rarely presents with peritoneal involvement. As such, its diagnosis in the emergency department (ED) based on a clinical presentation of gastrointestinal symptoms is extremely challenging. Yet, reaching such a diagnosis in the ED is crucial for avoiding unnecessary surgical intervention and initiating early glucocorticoid therapy to maximise patient outcomes. Here, we report a case of newly diagnosed SLE in a 28-year-old lady who presented atypically and unusually with abdominal pain and ascites. She required extensive but methodical investigations, and was eventually diagnosed with lupus mesenteric vasculitis with underlying newly diagnosed SLE in the ED. The patient was promptly treated with methylprednisolone resulting in marked clinical improvement. Emergency physicians should be mindful of abdominal pain with ascites as an extremely rare but important clinical presentation of SLE. Early diagnosis and commencement of glucocorticoid therapy in these patients are crucial in halting disease progression and averting the need for surgical intervention.

Guidelines for COVID-19 Laboratory Testing for Emergency Departments From the New Diagnostic Technology Team of the Taiwan Society of Emergency Medicine.

COVID-19 tests have different turnaround times (TATs), accuracy levels, and limitations, which emergency physicians should be aware of. Nucleic acid amplification tests (NAATs) can be divided into standard high throughput tests and rapid molecular diagnostic tests at the point of care (POC). The standard NAAT has the advantages of high throughput and high accuracy with a TAT of 3-4 hours. The POC molecular test has the same advantages of high accuracy as standard high throughput PCR, but can be done in 13-45 minutes. Roche cobas Liat is the most commonly used machine in Taiwan, displaying 99%-100% sensitivity and 100% specificity, respectively. Abbott ID NOW is an isothermal PCR-based POC machine with a sensitivity of 79% and a specificity of 100%. A high rate of false positives and false negatives is associated with rapid antigen testing. Antibody testing is mostly used as part of public health surveys and for testing for immunity.

Does medical disparity exist while treating severe mental illness patients with acute appendicitis in emergency departments? A real-world database study.

BACKGROUND: Patients with severe mental illness (SMI) have a shorter life expectancy and have been considered by the World Health Organization (WHO) as a vulnerable group. As the causes for this mortality gap are complex, clarification regarding the contributing factors is crucial to improving the health care of SMI patients. Acute appendicitis is one of the most common indications for emergency surgery worldwide. A higher perforation rate has been found among psychiatric patients. This study aims to evaluate the differences in appendiceal perforation rate, emergency department (ED) management, in-hospital outcomes, and in-hospital expenditure among acute appendicitis patients with or without SMI via the use of a multi-centre database. METHODS: Relying on Chang Gung Research Database (CGRD) for data, we selectively used its data from January 1st, 2007 to December 31st, 2017. The diagnoses of acute appendicitis and SMI were confirmed by combining ICD codes with relevant medical records. A non-SMI patient group was matched at the ratio of 1:3 by using the Greedy algorithm. The outcomes were appendiceal perforation rate, ED treatment, in-hospital outcome, and in-hospital expenditure. RESULTS: A total of 25,766 patients from seven hospitals over a span of 11 years were recruited; among them, 11,513 were excluded by criteria, with 14,253 patients left for analysis. SMI group was older (50.5 vs. 44.4 years, p < 0.01) and had a higher percentage of females (56.5 vs. 44.4%, p = 0.01) and Charlson Comorbidity Index. An analysis of the matched group has revealed that the SMI group has a higher unscheduled 72-hour revisit to ED (17.9 vs. 10.4%, p = 0.01). There was no significant difference in appendiceal perforation rate, ED treatment, in-hospital outcome, and in-hospital expenditure. CONCLUSIONS: Our study demonstrated no obvious differences in appendiceal perforation rate, ED management, in-hospital outcomes, and in-hospital expenditure among SMI and non-SMI patients with acute appendicitis. A higher unscheduled 72-hour ED revisit rate prior to the diagnosis of acute appendicitis in the SMI group was found. ED health providers need to be cautious when it comes to SMI patients with vague symptoms or unspecified abdominal complaints.

Shock Index Is a Validated Prediction Tool for the Short-Term Survival of Advanced Cancer Patients Presenting to the Emergency Department.

Advanced cancer patients who are not expected to survive past the short term can benefit from early initiation of palliative care in the emergency department (ED). This discussion, however, requires accurate prognostication of their short-term survival. We previously found in our retrospective study that shock index (SI) is an ideal risk stratification tool in predicting the 60-day mortality risk of advanced cancer patients presenting to the ED. This study is a follow-up prospective validation study conducted from January 2019 to April 2021. A total of 410 advanced cancer patients who presented to the ED of a medical centre and could be followed-up feasibly were recruited. Univariate and multivariable logistic regression analyses were performed with receiver operator calibrating (ROC) curve analysis. Non-survivors had significantly lower body temperatures, higher pulse rates, higher respiratory rates, lower blood pressures, and higher SI. Each 0.1 increment of SI increased the odds of 60-day mortality by 1.591. Area under ROC curve was 0.7819. At optimal cut-off of 0.94, SI had 66.10% accuracy. These results were similar to our previous study, thus validating the use of SI in predicting the 60-day mortality of advanced cancer patients presenting to the ED. Identified patients may be offered palliative care.

Bacterial Pericarditis Caused by Penetration of a Migrated Biliary Stent from the Lateral Segment of the Liver: A Case Report.

Endoscopic biliary stent insertion is a well-established procedure that is indispensable in the management of various benign and malignant biliary disorders, and one that helps prevent mortality related to invasive surgical procedures. We report a rare case of the distal migration of a biliary stent outside the abdomen to the pericardium, inducing constrictive pericarditis and septic shock. This case alerts clinicians to be aware of potential adverse events that can lead to unfavorable patient outcomes. Such adverse events can be effectively avoided through early detection and intervention.

Comparison of the diagnostic accuracy of monocyte distribution width and procalcitonin in sepsis cases in the emergency department: a prospective cohort study.

BACKGROUND: Early diagnosis and treatment of patients with sepsis reduce mortality significantly. In terms of exploring new diagnostic tools of sepsis, monocyte distribution width (MDW), as part of the white blood cell (WBC) differential count, was first reported in 2017. MDW greater than 20 and abnormal WBC count together provided a satisfactory accuracy and was proposed as a novel diagnostic tool of sepsis. This study aimed to compare MDW and procalcitonin (PCT)'s diagnostic accuracy on sepsis in the emergency department. METHODS: This was a single-center prospective cohort study. Laboratory examinations including complete blood cell and differentiation count (CBC/DC), MDW, PCT were obtained while arriving at the ED. We divided patients into non-infection, infection without systemic inflammatory response syndrome (SIRS), infection with SIRS, and sepsis-3 groups. This study's primary outcome is the sensitivity and specificity of MDW, PCT, and MDW + WBC in differentiating septic and non-septic patients. In addition, the cut-off value for MDW was established to maximize sensitivity at an optimal level of specificity. RESULTS: From May 2019 to September 2020, 402 patients were enrolled for data analysis. Patient number in each group was: non-infection 64 (15.9%), infection without SIRS 82 (20.4%), infection with SIRS 202 (50.2%), sepsis-3 15 (7.6%). The AUC of MDW, PCT, and MDW + WBC to predict infection with SIRS was 0.753, 0.704, and 0.784, respectively (p < 0.01). The sensitivity, specificity, PPV, and NPV of MDW using 20 as the cutoff were 86.4%, 54.2%, 76.4%, and 70%, compared to 32.9%, 88%, 82.5%, and 43.4% using 0.5 ng/mL as the PCT cutoff value. On combing MDW and WBC count, the sensitivity and NPV further increased to 93.4% and 80.3%, respectively. In terms of predicting sepsis-3, the AUC of MDW, PCT, and MDW + WBC was 0.72, 0.73, and 0.70, respectively. MDW, using 20 as cutoff, exhibited sensitivity, specificity, PPV, and NPV of 90.6%, 37.1%, 18.7%, and 96.1%, respectively, compared to 49.1%, 78.6%, 26.8%, and 90.6% when 0.5 ng/mL PCT was used as cutoff. CONCLUSIONS: In conclusion, MDW is a more sensitive biomarker than PCT in predicting infection-related SIRS and sepsis-3 in the ED. MDW < 20 shows a higher NPV to exclude sepsis-3. Combining MDW and WBC count further improves the accuracy in predicting infection with SIRS but not sepsis-3. Trial registration The study was retrospectively registered to the ClinicalTrial.gov (NCT04322942) on March 26th, 2020.

Intravenous CT Contrast Media and Acute Kidney Injury: A Multicenter Emergency Department-based Study.

Background Although the historical risk of acute kidney injury (AKI) after intravenous administration of contrast media might be overstated, the risk in patients with impaired kidney function remains a concern. Purpose To investigate whether intravenous contrast media administration during CT is associated with a higher risk of AKI and further hemodialysis compared with the risk in patients undergoing unenhanced CT. Materials and Methods This retrospective study evaluated patients who underwent contrast-enhanced or unenhanced CT in five Taiwanese emergency departments between 2009 and 2016. The outcomes were AKI within 48-72 hours after CT, AKI within 48 hours to 1 week after CT, or further hemodialysis within 1 month after CT. The associations between contrast media exposure and outcome were estimated by using an overlap propensity score weighted generalized regression model. Subgroup analyses were performed according to the estimated glomerular filtration rate (eGFR). Results The study included 68 687 patients (median age, 68 years; interquartile range, 53-74 years; 39 995 men) with (n = 31 103) or without (n = 37 584) exposure to contrast media. After propensity score weighting, contrast media exposure was associated with higher risk of AKI within 48-72 hours after CT (odds ratio [OR], 1.16; 95% CI: 1.04, 1.29; P = .007) but no significant risk at 48 hours to 1 week after CT (OR, 1.00; 95% CI: 0.93, 1.08; P = .90). Among patients with eGFR less than 30 mL/min/1.73 m2, exposure to contrast media was associated with a higher AKI risk (48-72 hours after CT: OR, 1.36; 95% CI: 1.09, 1.70; P = .007) (48 hours-1 week after CT: OR, 1.49; 95% CI: 1.27, 1.74; P < .001) and a higher risk of hemodialysis (OR, 1.36; 95% CI: 1.09, 1.70; P = .008). For patients with eGFR greater than 45 mL/min/1.73.m2, contrast media exposure was not associated with higher AKI risk (P > .05). Conclusion Contrast-enhanced CT was associated with higher risk of acute kidney injury and further hemodialysis among Taiwanese patients with an estimated glomerular filtration rate (eGFR) of less than 30 mL/min/1.73 m2 but not those with an eGFR of more than 45 mL/min/1.73 m2. © RSNA, 2021 Online supplemental material is available for this article.

Two-stage prediction model for in-hospital mortality of patients with influenza infection.

BACKGROUND: Infleunza is a challenging issue in public health. The mortality and morbidity associated with epidemic and pandemic influenza puts a heavy burden on health care system. Most patients with influenza can be treated on an outpatient basis but some required critical care. It is crucial for frontline physicians to stratify influenza patients by level of risk. Therefore, this study aimed to create a prediction model for critical care and in-hospital mortality. METHODS: This retrospective cohort study extracted data from the Chang Gung Research Database. This study included the patients who were diagnosed with influenza between 2010 and 2016. The primary outcome of this study was critical illness. The secondary analysis was to predict in-hospital mortality. A two-stage-modeling method was developed to predict hospital mortality. We constructed a multiple logistic regression model to predict the outcome of critical illness in the first stage, then S1 score were calculated. In the second stage, we used the S1 score and other data to construct a backward multiple logistic regression model. The area under the receiver operating curve was used to assess the predictive value of the model. RESULTS: In the present study, 1680 patients met the inclusion criteria. The overall ICU admission and in-hospital mortality was 10.36% (174 patients) and 4.29% (72 patients), respectively. In stage I analysis, hypothermia (OR = 1.92), tachypnea (OR = 4.94), lower systolic blood pressure (OR = 2.35), diabetes mellitus (OR = 1.87), leukocytosis (OR = 2.22), leukopenia (OR = 2.70), and a high percentage of segmented neutrophils (OR = 2.10) were associated with ICU admission. Bandemia had the highest odds ratio in the Stage I model (OR = 5.43). In stage II analysis, C-reactive protein (OR = 1.01), blood urea nitrogen (OR = 1.02) and stage I model's S1 score were assocaited with in-hospital mortality. The area under the curve for the stage I and II model was 0.889 and 0.766, respectively. CONCLUSIONS: The two-stage model is a efficient risk-stratification tool for predicting critical illness and mortailty. The model may be an optional tool other than qSOFA and SIRS criteria.

Shock Index: A Simple and Effective Clinical Adjunct in Predicting 60-Day Mortality in Advanced Cancer Patients at the Emergency Department.

Deciding between palliative and overly aggressive therapies for advanced cancer patients who present to the emergency department (ED) with acute issues requires a prediction of their short-term survival. Various scoring systems have previously been studied in hospices or intensive care units, though they are unsuitable for use in the ED. We aim to examine the use of a shock index (SI) in predicting the 60-day survival of advanced cancer patients presenting to the ED. Identified high-risk patients and their families can then be counseled accordingly. Three hundred and five advanced cancer patients who presented to the EDs of three tertiary hospitals were recruited, and their data retrospectively analyzed. Relevant data regarding medical history and clinical presentation were extracted, and respective shock indices calculated. Multivariate logistic regression analyses were performed. Receiver operating characteristic (ROC) curves were plotted to evaluate the predictive performance of the SI. Nonsurvivors within 60 days had significantly lower body temperatures and blood pressure, as well as higher pulse rates, respiratory rates, and SI. Each 0.1 SI increment had an odds ratio of 1.39 with respect to 60-day mortality. The area under the ROC curve was 0.7511. At the optimal cut-off point of 0.94, the SI had 81.38% sensitivity and 73.11% accuracy. This makes the SI an ideal evaluation tool for rapidly predicting the 60-day mortality risk of advanced cancer patients presenting to the ED. Identified patients can be counseled accordingly, and they can be assisted in making informed decisions on the appropriate treatment goals reflective of their prognoses.

Prognostic accuracy of SIRS criteria and qSOFA score for in-hospital mortality among influenza patients in the emergency department.

BACKGROUND: The seasonal influenza epidemic is an important public health issue worldwide. Early predictive identification of patients with potentially worse outcome is important in the emergency department (ED). Similarly as with bacterial infection, influenza can cause sepsis. This study was conducted to investigate the effectiveness of the Systemic Inflammatory Response Syndrome (SIRS) criteria and the quick Sequential Organ Failure Assessment (qSOFA) score as prognostic predictors for ED patients with influenza. METHODS: This single-center, retrospective cohort study investigated data that was retrieved from a hospital-based research database. Adult ED patients (age ≥ 18 at admission) with laboratory-proven influenza from 2010 to 2016 were included for data analysis. The initial SIRS and qSOFA scores were both collected. The primary outcome was the utility of each score in the prediction of in-hospital mortality. RESULTS: For the study period, 3561 patients met the study inclusion criteria. The overall in-hospital mortality was 2.7% (95 patients). When the qSOFA scores were 0, 1, 2, and 3, the percentages of in-hospital mortality were 0.6, 7.2, 15.9, and 25%, respectively. Accordingly, the odds ratios (ORs) were 7.72, 11.92, and 22.46, respectively. The sensitivity and specificity was 24 and 96.2%, respectively, when the qSOFA score was ≥2. However, the SIRS criteria showed no significant associations with the primary outcome. The area under the receiver operating characteristic curve (AUC) was 0.864, which is significantly higher than that with SIRS, where the AUC was 0.786 (P < 0.01). CONCLUSIONS: The qSOFA score potentially is a useful prognostic predictor for influenza and could be applied in the ED as a risk stratification tool. However, qSOFA may not be a good screening tool for triage because of its poor sensitivity. The SIRS criteria showed poor predictive performance in influenza for mortality as an outcome. Further research is needed to determine the role of these predictive tools in influenza and in other viral infections.

Step-down units are cost-effective alternatives to coronary care units with non-inferior outcomes in the management of ST-elevation myocardial infarction patients after successful primary percutaneous coronary intervention.

Percutaneous coronary interventions (PCIs) within a door-to-balloon timing of 90 min have greatly decreased mortality and morbidity of ST-elevation myocardial infarction (STEMI) patients. Post-PCI, they are routinely transferred into the coronary care unit (CCU) regardless of the severity of their condition, resulting in frequent CCU overcrowding. This study assesses the feasibility of step-down units (SDUs) as an alternative to CCUs in the management of STEMI patients after successful PCI, to alleviate CCU overcrowding. Criteria of assessment include in-hospital complications, length of stay, cost-effectiveness, and patient outcomes up to a year after discharge from hospital. A retrospective case-control study was done using data of 294 adult STEMI patients admitted to the emergency departments of two training and research hospitals and successfully underwent primary PCI from 1 January 2014 to 31 December 2015. Patients were followed up for a year post-discharge. Student t test and χ2 test were done as univariate analysis to check for statistical significance of p < 0.05. Further regression analysis was done with respect to primary outcomes to adjust for major confounders. Patients managed in the SDU incurred significantly lower inpatient costs (p = 0.0003). No significant differences were found between the CCU and SDU patients in terms of patient characteristics, PCI characteristics, in-hospital complications, length of stay, and patient outcomes up to a year after discharge. The SDU is a viable cost-effective option for managing STEMI patients after successful primary PCI to avoid CCU overcrowding, with non-inferior patient outcomes as compared to the CCU.

Mechanistic study of the cause of decreased blood 1,25-Dihydroxyvitamin D in sepsis.

BACKGROUND: Vitamin D deficiency, determined by blood levels of 25-hydroxyvitamin D [25(OH) D, i.e. the major vitamin D form in blood], has been shown to associate with all-cause mortalities. We recently demonstrated that blood levels of 1,25-dihydroxyvitamin D [1,25(OH)2D, i.e. the active vitamin D] were significantly lower in non-survivors compared to survivors among sepsis patients. Unexpectedly, despite the well documented roles of 1,25(OH)2D in multiple biological functions such as regulation of immune responses, stimulation of antimicrobials, and maintenance of barrier function, 1,25(OH)2D supplementation failed to improve disease outcomes. These previous findings suggest that, in addition to 1,25(OH)2D deficiency, disorders leading to the 1,25(OH)2D deficiency also contribute to mortality among sepsis patients. Therefore, this study investigated the mechanisms leading to sepsis-associated 1,25(OH)2D deficiency. METHODS: We studied mechanisms known to regulate kidney 25-hydroxylvitamin D 1α-hydroxylase which physiologically catalyzes the conversion of 25(OH) D into 1,25(OH)2D. Such mechanisms included parathyroid hormone (PTH), insulin-like growth factor 1 (IGF-1), fibroblast growth factor 23 (FGF-23), and kidney function. RESULTS: We demonstrated in both human subjects and mice that sepsis-associated 1,25(OH)2D deficiency could not be overcome by increased production of PTH which stimulates 1α-hydroxylase. Further studies showed that this failure of PTH to maintain blood 1,25(OH)2D levels was associated with decreased blood levels of IGF-1, increased blood levels of FGF-23, and kidney failure. Since the increase in blood levels of FGF-23 is known to associate with kidney failure, we further investigated the mechanisms leading to sepsis-induced decrease in blood levels of IGF-1. Our data showed that blood levels of growth hormone, which stimulates IGF-1 production in liver, were increased but could not overcome the IGF-1 deficiency. Additionally, we found that the inability of growth hormone to restore the IGF-1 deficiency was associated with suppressed expression and signaling of growth hormone receptor in liver. CONCLUSIONS: Because FGF-23 and IGF-1 have multiple biological functions besides their role in regulating kidney 1α-hydroxylase, our data suggest that FGF-23 and IGF-1 are warranted for further investigation as potential agents for the correction of 1,25(OH)2D deficiency and for the improvement of survival among sepsis patients.

Predicting need for intensive care unit admission in adult emphysematous pyelonephritis patients at emergency departments: comparison of five scoring systems.

This study assesses the performance of National Early Warning Score (NEWS), Quick Sepsis-related Organ Failure Assessment (qSOFA), Modified Early Warning Score (MEWS), Rapid Emergency Medicine Score (REMS), and Rapid Acute Physiology Score (RAPS) in predicting emphysematous pyelonephritis (EPN) patients' need for intensive care unit (ICU) admission. A retrospective analysis was conducted at four training and research hospitals' emergency departments (EDs) on all EPN adult patients from January 2007 to August 2017. Data extracted were used to calculate raw scores for five physiologic scoring systems. Mann-Whitney U tests and χ2 tests were done for numerical and categorical variables respectively to examine differences between characteristics of ICU and non-ICU patient populations. Predictability of ICU admission was evaluated with AUROC analysis. ICU patients had lower GCS scores, SpO2, platelet counts, and estimated glomerular filtration rate; and higher bands, blood urea nitrogen, creatinine, and incidences of septic shock and nephrectomy. NEWS performed best, with 73.85% accuracy at optimal cut-off of 3. In this multicentre ED EPN series, we recommend using NEWS in early identification of critical EPN patients and advance planning for ICU admission. This would reduce delays in ICU transfer and ultimately improve patient outcomes.

In Vivo Generation of Gut-Homing Regulatory T Cells for the Suppression of Colitis.

Current therapies for gut inflammation have not reached the desired specificity and are attended by unintended immune suppression. This study aimed to provide evidence for supporting a hypothesis that direct in vivo augmentation of the induction of gut-homing regulatory T (Treg) cells is a strategy of expected specificity for the treatment of chronic intestinal inflammation (e.g., inflammatory bowel disease). We showed that dendritic cells (DCs), engineered to de novo produce high concentrations of both 1,25-dihydroxyvitamin D, the active vitamin D metabolite, and retinoic acid, an active vitamin A metabolite, augmented the induction of T cells that express both the regulatory molecule Foxp3 and the gut-homing receptor CCR9 in vitro and in vivo. In vivo, the newly generated Ag-specific Foxp3+ T cells homed to intestines. Additionally, transfer of such engineered DCs robustly suppressed ongoing experimental colitis. Moreover, CD4+ T cells from spleens of the mice transferred with the engineered DCs suppressed experimental colitis in syngeneic hosts. The data suggest that the engineered DCs enhance regulatory function in CD4+ T cell population in peripheral lymphoid tissues. Finally, we showed that colitis suppression following in vivo transfer of the engineered DCs was significantly reduced when Foxp3+ Treg cells were depleted. The data indicate that maximal colitis suppression mediated by the engineered DCs requires Treg cells. Collectively, our data support that DCs de novo overproducing both 1,25-dihydroxyvitamin D and retinoic acid are a promising novel therapy for chronic intestinal inflammation.

Comparison of the Mortality in Emergency Department Sepsis Score, Modified Early Warning Score, Rapid Emergency Medicine Score and Rapid Acute Physiology Score for predicting the outcomes of adult splenic abscess patients in the emergency department.

BACKGROUND: Splenic abscess is rare but has mortality rates as high as 14% even with recent improvements in management. Early and appropriate intervention may improve patient outcomes, yet at present there is no identified method that can predict mortality risk rapidly and accurately for emergency physicians, surgeons, and intensivists to decide on the ideal course of action. OBJECTIVE: This study aims to evaluate the performance of Mortality in Emergency Department Sepsis Score (MEDS), Modified Early Warning Score (MEWS), Rapid Emergency Medicine Score (REMS) and Rapid Acute Physiology Score (RAPS) for predicting the mortality risk of adult splenic abscess patients. This will expedite decision making in the emergency department (ED) to increase survival rates and help avoid unnecessary splenectomies. METHODS: Data of 114 adult patients admitted to the EDs of 4 research and training hospitals who had undergone an abdominal contrast CT scan and diagnosed with splenic abscess between Jan 2000 and April 2015 were analyzed. The MEDS, MEWS, REMS, and RAPS and their corresponding mortality risks were calculated, with their abilities to predict patient mortality assessed through receiver operating characteristic curve analysis and calibration analysis. RESULTS: MEDS was found to be the best performing scoring system across all indicators, with sensitivity, specificity, and accuracy of 92.86%, 88.00%, and 88.60% respectively; its area under curve for AUROC analysis was 0.92. With a cutoff value of 8, negative predictive value of MEDS was 98.88%. CONCLUSION: Our series is the largest multicenter study in adult ED patients with splenic abscess. The results from the present study show that MEDS is superior to MEWS, REMS and RAPS in predicting mortality, thus allowing earlier detection of critically ill adult ED splenic abscess patients. Therefore, we recommend that MEDS be used for predicting severity of illness and risk stratification in these patients.

Comparison of diagnostic accuracy in sepsis between presepsin, procalcitonin, and C-reactive protein: a systematic review and meta-analysis.

BACKGROUND: The soluble cluster of differentiation 14 (or presepsin) is a free fragment of glycoprotein expressed on monocytes and macrophages. Although many studies have been conducted recently, the diagnostic performance of presepsin for sepsis remains debated. We performed a systematic review and meta-analysis of the available literature to assess the accuracy of presepsin for the diagnosis of sepsis in adult patients and compared the performance between presepsin, C-reactive protein (CRP), and procalcitonin (PCT). METHODS: A comprehensive systemic search was conducted in PubMed, EMBASE, and Google Scholar for studies that evaluated the diagnostic accuracy of presepsin for sepsis until January 2017. The hierarchical summary receiver operating characteristic method was used to pool individual sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and area under the receiver operating characteristic curve (AUC). RESULTS: Eighteen studies, comprising 3470 patients, met our inclusion criteria. The pooled diagnosis sensitivity and specificity of presepsin for sepsis were 0.84 (95% CI 0.80-0.87) and 0.76 (95% CI 0.67-0.82), respectively. Furthermore, the pooled DOR, PLR, NLR, and AUC were 16 (95% CI 10-25), 3.4 (95% CI 2.5-4.6), 0.22 (95% CI 0.17-0.27), and 0.88 (95% CI 0.85-0.90), respectively. Significant heterogeneity was found in both sensitivities (Cochrane Q = 137.43, p < 0.001, I 2 = 87.63%) and specificities (Cochrane Q = 180.76, p < 0.001, I 2 = 90.60%). Additionally, we found no significant difference between presepsin and PCT (AUC 0.87 vs. 0.86) or CRP (AUC 0.85 vs. 0.85). However, for studies conducted in ICU, the pooled sensitivity of presepsin was found to be higher than PCT (0.88, 95% CI 0.82-0.92 vs. 0.75, 95% CI 0.68-0.81), while the pooled specificity of presepsin was lower than PCT (0.58, 95% CI 0.42-0.73 vs. 0.75, 95% CI 0.65-0.83). CONCLUSION: Based on the results of our meta-analysis, presepsin is a promising marker for diagnosis of sepsis as PCT or CRP, but its results should be interpreted more carefully and cautiously since too few studies were included and those studies had high heterogeneity between them. In addition, continuing re-evaluation during the course of sepsis is advisable.