A Low-Latency DNN Accelerator Enabled by DFT-Based Convolution Execution Within Crossbar Arrays.

Analog resistive random access memory (RRAM) devices enable parallelized nonvolatile in-memory vector-matrix multiplications for neural networks eliminating the bottlenecks posed by von Neumann architecture. While using RRAMs improves the accelerator performance and enables their deployment at the edge, the high tuning time needed to update the RRAM conductance states adds significant burden and latency to real-time system training. In this article, we develop an in-memory discrete Fourier transform (DFT)-based convolution methodology to reduce system latency and input regeneration. By storing the static DFT/inverse DFT (IDFT) coefficients within the analog arrays, we keep digital computational operations using digital circuits to a minimum. By performing the convolution in reciprocal Fourier space, our approach minimizes connection weight updates, which significantly accelerates both neural network training and interference. Moreover, by minimizing RRAM conductance update frequency, we mitigate the endurance limitations of resistive nonvolatile memories. We show that by leveraging the symmetry and linearity of DFT/IDFTs, we can reduce the power by 1.57 × for convolution over conventional execution. The designed hardware-aware deep neural network (DNN) inference accelerator enhances the peak power efficiency by 28.02 × and area efficiency by 8.7 × over state-of-the-art accelerators. This article paves the way for ultrafast, low-power, compact hardware accelerators.

Detection of cytotoxins by sandwich-ELISA for discrimination of cobra envenomation and indication of necrotic severity.

Snake envenoming is both a healthcare and socioeconomic problem for developing countries and underserved communities. In Taiwan, clinical management of Naja atra envenomation is a major challenge, since cobra venom-induced symptoms are usually confused with hemorrhagic snakebites and current antivenom treatments do not effectively prevent venom-induced necrosis for which early surgical debridement should be administered. Identification and validation of biomarkers of cobra envenomation is critical for progress in setting a realistic goal for snakebite management in Taiwan. Previously, cytotoxin (CTX) was determined as one of potential biomarker candidates; however, its ability to discriminate cobra envenoming remains to be verified, especially in clinical practice. In this study, we selected a monoclonal single-chain variable fragment (scFv) and a polyclonal antibody to develop a sandwich enzyme-linked immunosorbent assay (ELISA) for CTX detection, which successfully recognized CTX from N. atra venom over that from other snake species. Using this specific assay, the CTX concentration in envenoming mice was shown to remain consistent in about 150 ng/mL during the 2-hour post-injection period. The measured concentration was highly correlated with the size of local necrosis in mouse dorsal skin, which the correlation coefficient is about 0.988. Furthermore, our ELISA method displayed 100 % of specificity and sensitivity in discriminating cobra envenoming among snakebite victims through CTX detection and the level of CTX in victim plasma was ranged from 5.8 to 253.9 ng/mL. Additionally, patients developed tissue necrosis at plasma CTX concentrations higher than 150 ng/mL. Thus, CTX not only serves as a verified biomarker for discrimination of cobra envenoming but also a potential indicator of severity of local necrosis. In this context, detection of CTX may facilitate reliable identification of envenoming species and improve snakebite management in Taiwan.

Immunoprofiling of Equine Plasma against Deinagkistrodon acutus in Taiwan: Key to Understanding Differential Neutralization Potency in Immunized Horses.

Snakebite envenoming is a public health issue linked to high mortality and morbidity rates worldwide. Although antivenom has been the mainstay treatment for envenomed victims receiving medical care, the diverse therapeutic efficacy of the produced antivenom is a major limitation. Deinagkistrodon acutus is a venomous snake that poses significant concern of risks to human life in Taiwan, and successful production of antivenom against D. acutus envenoming remains a considerable challenge. Among groups of horses subjected to immunization schedules, few or none subsequently meet the quality required for further scale-up harvesting. The determinants underlying the variable immune responses of horses to D. acutus venom are currently unknown. In this study, we assessed the immunoprofiles of high-potency and low-potency horse plasma against D. acutus venom and explored the conspicuous differences between these two groups. Based on the results of liquid chromatography with tandem mass spectrometry (LC-MS/MS), acutolysin A was identified as the major component of venom proteins that immunoreacted differentially with the two plasma samples. Our findings indicate underlying differences in antivenoms with variable neutralization efficacies, and may provide valuable insights for improvement of antivenom production in the future.

Development of a Monoclonal scFv against Cytotoxin to Neutralize Cytolytic Activity Induced by Naja atra Venom on Myoblast C2C12 Cells.

The Taiwanese cobra, Naja atra, is a clinically significant species of snake observed in the wild in Taiwan. Victims bitten by N. atra usually experience severe pain and local tissue necrosis. Although antivenom is available for treatment of cobra envenomation, its neutralization potency against cobra-induced necrosis is weak, with more than 60% of cobra envenoming patients developing tissue necrosis after antivenom administration. The present study found that cytotoxin (CTX) is a key component of N. atra venom responsible for cytotoxicity against myoblast cells. Anti-CTX IgY was generated in hens, and the spleens of these hens were used to construct libraries for the development of single chain variable fragments (scFv). Two anti-CTX scFv, S1 and 2S7, were selected using phage display technology and biopanning. Both polyclonal IgY and monoclonal scFv S1 reacted specifically with CTX in cobra venom. In a cell model assay, the CTX-induced cytolytic effect was inhibited only by monoclonal scFv S1, not by polyclonal IgY. Moreover, the neutralization potency of scFv S1 was about 3.8 mg/mg, approximately three times higher than that of conventional freeze-dried neurotoxic antivenom (FNAV). Collectively, these results suggest that scFv S1 can effectively neutralize CTX-induced cytotoxicity and, when combined with currently available antivenom, can improve the potency of the latter, thereby preventing tissue damage induced by cobra envenoming.

Methanol Intoxication After Suicidal Ingestion of Liquid Rodenticides: A Report of Two Cases.

Methanol is highly toxic to humans. Although methanol poisoning is not uncommon in developing countries, poisoning caused by ingestion of commercial products containing undeclared methanol has rarely been reported. Herein, we describe two patients who experienced methanol poisoning after ingestion of liquid rodenticides. A 39-year-old woman attempted suicide by ingesting liquid rodenticide which contained bromadiolone. She developed high anion gap metabolic acidosis and coagulopathy. Methanol poisoning was confirmed 20 hours later. She received oral ethanol therapy and hemodialysis. Vitamin K1 was also administered. She did not develop any hemorrhage or visual impairment and was discharged after 11 days. The rodenticide sample was tested and found to have a methanol concentration of 324 g/L. In another case, a 62-year-old man ingested the same brand of rodenticide. Laboratory data showed mild metabolic acidosis with an increased osmol gap, suggestive of methanol poisoning. He received hemodialysis and eventually recovered without sequelae. Liquid rodenticide may contain methanol as a solvent. Ingestion of a methanol-containing commercial product without a clear label can result in a considerable delay in diagnosis and management. Methanol poisoning should be considered for patients who present with unexplained metabolic acidosis following exposure to liquid rodenticides or other liquid commercial products.

Sudden quadriparesis after non-overdose local anesthesia.

BACKGROUND: A well-known anesthetic, lidocaine is the most widely used local anesthetic. Local anesthetic systemic toxicity (LAST) is a life-threatening event with common and prominent presentations of central nervous system (CNS) toxicity and cardiovascular toxicity. The most frequent and prominent early warning signs and symptoms of LAST are central nervous system symptoms. While rare, cases quadriparesis after the administration of lidocaine has been reported. CASE PRESENTATION: In this paper, we report a very rare case of quadriparesis after local anesthesia administration for vocal cord cyst-removal surgery, which dramatically improved after treatment. LAST can occur during various routes of lidocaine administration, such as local spray. A possible mechanism of our case could be the local diffusion of lidocaine to the spinal cord, which caused the symptoms to mimic anterior cord syndrome. CONCLUSIONS: Our case presented a favorable outcome following the administration of intravenous lipid emulsion (ILE) for non-over dose local anesthetic drug induced spinal cord inhibition symptoms. These findings highlight the need for further research on the use of ILE to reverse LAST and other adverse effects of local anesthetics.

The acute paraquat poisoning mortality (APPM) score to predict the risk of death in paraquat-poisoned patients.

CONTEXT: Mortality prediction in paraquat poisoning is a major issue since most prediction rules are inapplicable if the exact ingestion time cannot be determined and/or the serum paraquat concentration is not readily available, as in most countries. Therefore, we aimed to develop and validate a new prediction rule not requiring these two parameters. METHODS: We designed a 10-year observational cohort study including all consecutive paraquat-poisoned patients managed in two Taiwanese hospitals. We built one cohort to define and one cohort to validate this prediction rule. Parameters independently related to mortality determined using a multivariate analysis were used to formulate the Acute Paraquat Poisoning Mortality (APPM) score. RESULTS: Overall, 321 paraquat-poisoned patients were included, 156 in the derivation and 165 in the validation cohort. Mortality rates in the derivation and validation cohorts were 73% and 81%, respectively (p = 0.20). The three parameters chosen of 28-day mortality at presentation were urine paraquat level >10 ppm (using a colorimetric sodium dithionite-based test; odds ratio (OR), 12.70; 95% confidence interval (CI), 2.64-61.24), white blood cells >13.0 G/L (OR, 5.50; CI, 1.41-21.48) and blood glucose >140 mg/dL [7.8 mmol/L] (OR, 7.45; CI, 1.70-32.86). In the derivation cohort, the area under the ROC curve (AUC-ROC) of the APPM score did not significantly differ from AUC-ROCs of serum paraquat (0.95, p = 0.25) and the Severity Index of Paraquat Poisoning (0.95, p = 0.33). AUC-ROCs of the APPM score in the derivation and validation cohorts were 0.91 and 0.94, respectively. CONCLUSION: We built and validated a reliable score to predict 28-day mortality in paraquat-poisoned patients at presentation, independently from the ingestion time and serum paraquat measurement.

A novel flowchart to predict mortality and analyse effectiveness of routinely used pharmacological regimens in paraquat poisoning.

Paraquat is responsible for an extremely high case-fatality rate poisoning. Mortality prediction remains a major issue since evidence to support benefits of routinely used treatments is lacking. We aimed to develop an easy-to-use prediction flowchart not requiring the ingestion time, for which accuracy is frequently questionable, and to evaluate the effectiveness of routinely used pharmacological therapies on mortality. We designed a two-centre cohort study including consecutive paraquat-poisoned adults with confirmed diagnosis based on serum/urine paraquat measurement. We built a flowchart using a multivariate analysis of death predictors and analysed the outcome according to the administered therapies. Overall, 256 patients were enrolled. Mortality rate was 75%. Independent death predictors on admission were serum creatinine (odds ratio [OR], 5.07; 95% confidence interval [CI], 1.97-13.05) and serum paraquat concentration (OR, 2.26; CI, 1.66-3.09). The area-under-the flowchart curve was 0.91. Overall sensitivity and specificity were 81.5% and 94.8%, respectively. More survivors than non-survivors of severe poisoning received methylprednisolone (P = 0.04). While not significantly differing in severity, methylprednisolone-treated patients had better survival (P = 0.04). To conclude, we defined an efficient flowchart to predict mortality in paraquat poisoning at presentation, even if ingestion time is undetermined. Methylprednisolone seems effective to improve the outcome, especially in the most severe cases.

Snake venom proteome of Protobothrops mucrosquamatus in Taiwan: Delaying venom-induced lethality in a rodent model by inhibition of phospholipase A2 activity with varespladib.

Protobothrops mucrosquamatus, also known as the brown spotted pit viper or Taiwanese habu, is a medically significant venomous snake in Taiwan, especially in the northern area. To more fully understand the proteome profile of P. mucrosquamatus, we characterized its venom composition using a bottom-up proteomic approach. Whole venom components were fractionated by RP-HPLC and then analyzed by SDS-PAGE. Each protein band in gels was excised and subjected to protein identification by LC-MS/MS. A subsequent proteomic analysis revealed the presence of 61 distinct proteins belonging to 19 families in P. mucrosquamatus venom. Snake venom metalloproteinase (SVMP; 29.4%), C-type lectin (CLEC; 21.1%), snake venom serine protease (SVSP; 17.6%) and phospholipase A2 (PLA2; 15.9%) were the most abundant protein families, whereas several low-abundance proteins, categorized into eight protein families, were demonstrated in P. mucrosquamatus venom for the first time. Because PLA2 is known to make a major contribution to venom lethality, we evaluated whether the known PLA2 inhibitor, varespladib, was capable of preventing the toxic effects of P. mucrosquamatus venom. This small-molecule drug demonstrated the ability to inhibit PLA2 activity in vitro (IC50 = 101.3 nM). It also blunted lethality in vivo, prolonging survival following venom injection in a mouse model, but it showed limited potency against venom-induced local hemorrhage in this model. Our findings provide essential biological and pathophysiological insights into the composition of P. mucrosquamatus venom and suggest PLA2 inhibition as an adjunctive or alternative therapeutic strategy in the clinical management of P. mucrosquamatus envenoming in emergency medicine. SIGNIFICANCE: P. mucrosquamatus envenomation is a significant medical concern in Taiwan, especially in the northern region. Although antivenom is commonly used for rescuing P. mucrosquamatus envenoming, severe clinical events still occur, with more than 20% of cases requiring surgical intervention. Small-molecule therapy offers several advantages as a potential adjunctive, or even alternative, to antivenom treatment, such as heat stability, low antigenicity and ease of administration, among others. A deeper understanding of the venom proteome of P. mucrosquamatus would aid in the discovery of small-molecule drugs that could be repurposed to target specific venom proteins. Here, we applied a bottom-up proteomic approach to characterize the protein profile of P. mucrosquamatus venom. Varespladib, a small-molecule drug used to treat inflammatory disease, was repurposed to inhibit the toxicity of P. mucrosquamatus venom, and was shown to reduce the lethal effects of P. mucrosquamatus envenomation in a rodent model. Varespladib might be used as a first-aid therapeutic against P. mucrosquamatus envenoming in the pre-referral period and/or as an adjunctive agent administered together with anti-P. mucrosquamatus antivenom.

Incidence of intoxication events and patient outcomes in Taiwan: A nationwide population-based observational study.

BACKGROUND: Intoxicated patients were frequently managed in the emergency departments (ED) with few studies at national level. The study aimed to reveal the incidence, outcomes of intoxications and trend in Taiwan. METHODS: Adults admitted to an ED due to an intoxication event between 2006 and 2013 were identified using the Taiwan National Health Insurance Research Database. The rate of intoxication and severe intoxication events, mortality rate, hospital length of stay (LOS), and daily medical costs of these patients were analyzed. Changes over time were analyzed using Joinpoint models. Multivariable generalized regressions with GEE were used to assess the effect of sex, age, and presence of prior psychiatric illness. RESULTS: A total of 20,371 ED admissions due to intoxication events were identified during the study period, and the incidence decreased with annual percentage change of 4.7% from 2006 to 2013. The mortality rate, hospital LOS, and daily medical costs were not decreased over time. Males and geriatric patients had more severe intoxication events, greater mortality rates, and greater daily medical costs. Patients with psychiatric illnesses had higher mortality rates and a longer hospital LOS, but lower daily medical expenses. CONCLUSION: From 2006 to 2013, there was a decline in the incidence of ED admission for intoxication events in Taiwan. Males, geriatric patients, and those with psychiatric illnesses had greater risks for severe intoxication and mortality.

Does Hemoperfusion Increase Survival in Acute Paraquat Poisoning? A Retrospective Multicenter Study.

The efficacy of hemoperfusion (HP) in patients with acute paraquat poisoning (PQ) remains controversial. We conducted a multi-center retrospective study to include acute PQ-poisoned patients admitted to two tertiary medical centers between 2005 and 2015. We used the Severity Index of Paraquat Poisoning (SIPP) to stratify the severity of PQ-poisoned patients. The indication to start HP was a positive result for the semiquantitative urine PQ test and presentation to the hospital was within 24 h. Early HP was defined as the first session of HP performed within five hours of PQ ingestion. A total of 213 patients (100 HP group, 113 non-HP group) were eligible for the study. The overall 60-day mortality of poisoned patients was 75.6% (161/213). Multivariate Cox regression analysis showed no statistically significant difference in 60-day survival between HP and non-HP groups (95% confidence interval (CI): 0.84-1.63, p = 0.363). Further subgroup analysis in the HP group showed early HP (95%CI: 0.54-1.69, p = 0.880), and multiple secessions of HP (95%CI: 0.56-1.07, p = 0.124) were not significantly related to better survival. Among acute PQ-poisoned patients, this study found that HP was not associated with increased 60-day survival. Furthermore, neither early HP nor multiple secessions of HP were associated with survival.

Brain Computed Tomography in Stimulant Poisoning with Altered Consciousness.

BACKGROUND: Stimulant poisoning frequently causes altered mental status (AMS) and can result in severe cerebral vascular complications. The role of noncontrast brain computed tomography (CT) in acute stimulant-poisoned patients presenting with AMS remains unclear. OBJECTIVES: We examined the results and impacts of brain CT in acute stimulant-poisoned patients with AMS. METHODS: We performed a retrospective single-center study that included all adult patients who presented to the emergency department with stimulant poisoning and AMS (Glasgow coma scale [GCS] score <15) between January 1, 2010 and December 31, 2017. Patients who had concomitant head trauma or who presented with focal neurologic symptoms were excluded. The primary outcome was the rate of acute abnormalities on brain CT. The secondary outcomes were to identify factors that affected the decision to perform brain CT in stimulant-poisoned patients with AMS and whether obtaining the brain CT scan itself affected the patients' prognoses. RESULTS: The analysis included 66 patients, of whom 6 died from the poisoning. Noncontrast brain CT was performed in 31 patients and none had acute abnormalities. Patients who underwent brain CT were found to have worse GCS scores, higher body temperatures, higher intubation rates, higher admission rates, longer admission periods and intensive care unit stays, and a higher mortality rate. After adjusting for the propensity score, performing brain CT itself did not independently affect the patients' clinical outcomes. CONCLUSIONS: Nontrauma stimulant-poisoned patients presenting with AMS and without focal neurologic symptoms were unlikely to have acute abnormalities on brain CT. Patients who underwent brain CT scans had worse consciousness and greater disease severity.

Pathogenesis of local necrosis induced by Naja atra venom: Assessment of the neutralization ability of Taiwanese freeze-dried neurotoxic antivenom in animal models.

Naja atra envenomation is one of the most significant clinical snakebite concerns in Taiwan. Taiwanese freeze-dried neurotoxic antivenom (FNAV) is currently used clinically for the treatment of cobra snakebite, and has been shown to limit the mortality of cobra envenomation to less than 1%. However, more than half of victims (60%) require surgery because of local tissue necrosis, a major problem in patients with cobra envenomation. Although the importance of evaluating the neutralizing effect of FNAV on this pathology is recognized, whether FNAV is able to prevent the local necrosis extension induced by N. atra venom has not been investigated in detail. Cytotoxins (CTXs) are considered as the major components of N. atra venom that cause necrosis. In the current study, we isolated CTXs from whole cobra venom and used both whole venom and purified CTXs to develop animal models for assessing the neutralization potential of FNAV against venom necrotizing activity. Local necrotic lesions were successfully produced in mice using CTXs in place of whole N. atra venom. FNAV was able to rescue mice from a subcutaneously injected lethal dose of cobra venom; however, it was unable to prevent CTX-induced dermo-necrosis. Furthermore, using the minimal necrosis dose (MND) of CTXs and venom proteome data, we found a dose of whole N. atra venom suitable for FNAV and developed a workable protocol for inducing local necrosis in rodent models that successfully imitated the clinical circumstance of cobra envenoming. This information provides a more comprehensive understanding of the pathophysiology of N. atra envenomation, and serves as a guide for improving current antivenom strategies and advancing clinical snakebite management in Taiwan.

Snake venom proteome and immuno-profiling of the hundred-pace viper, Deinagkistrodon acutus, in Taiwan.

Deinagkistrodon acutus, also known as the hundred-pace viper or Chinese moccasin, is a clinically significant venomous snake in Taiwan. To address the lack of knowledge on the venom proteome of D. acutus, the venom composition was studied by a bottom-up proteomic approach combining reverse phase high-performance liquid chromatography, SDS-PAGE, and LC-MS/MS analysis. The immunoreactivity and cross-reactivity of Taiwanese freeze-dried D. acutus antivenom (DA-AV) and hemorrhagic antivenom (FH-AV) were investigated, as well. The proteomic analysis revealed the presence of 29 distinct proteins from D. acutus venom belonging to 8 snake venom protein families. Snake venom metalloproteinase (SVMP, 46.86%), C-type lectin (CLEC, 37.59%), phospholipase A2 (PLA2, 7.33%) and snake venom serine protease (SVSP, 6.62%) were the most abundant proteins. In addition to DA-AV, FH-AV also showed a profile of broad immunorecognition toward the venom of D. acutus. Remarkably, both antivenoms specifically reacted with the HPLC fractions containing SVMPs, and the titer was 5-10 times higher than fractions of other components. This information helps us to deeply understand the pathophysiology of D. acutus envenomation and guide us to development of more effective antivenom for clinical treatment.

Association of In-Hospital Mortality and Dysglycemia in Septic Patients.

BACKGROUND: The associations between dysglycemia and mortality in septic patients with and without diabetes are yet to be confirmed. Our aim was to analyze the association of diabetes and sepsis mortality, and to examine how dysglycemia (hyperglycemia, hypoglycemia and glucose variability) affects in-hospital mortality of patients with suspected sepsis in emergency department (ED) and intensive care units. METHODS: Clinically suspected septic patients admitted to ED were included, and stratified into subgroups according to in-hospital mortality and the presence of diabetes. We analyzed patients' demographics, comorbidities, clinical and laboratory parameters, admission glucose levels and severity of sepsis. Odds ratio of mortality was assessed after adjusting for possible confounders. The correlations of admission glucose and CoV (blood glucose coefficients of variation) and mortality in diabetes and non-diabetes were also tested. RESULTS: Diabetes was present in 58.3% of the patients. Diabetic patients were older, more likely to have end-stage renal disease and undergoing hemodialysis, but had fewer malignancies, less sepsis severity (lower Mortality in Emergency Department Sepsis Score), less steroid usage in emergency department, and lower in-hospital mortality rate (aOR:0.83, 95% CI 0.65-0.99, p = 0.044). Hyperglycemia at admission (glucose≥200 mg/dL) was associated with higher risks of in-hospital mortality among the non-diabetes patients (OR:1.83 vs. diabetes, 95% CI 1.20-2.80, p = 0.005) with the same elevated glucose levels at admission. In addition, CoV>30% resulted in higher risk of death as well (aOR:1.88 vs. CoV between 10 and 30, 95%CI 1.24-2.86 p = 0.003). CONCLUSIONS: This study indicates that while diabetes mellitus seems to be a protective factor in sepsis patients, hyper- or hypoglycemia status on admission, and increased blood glucose variation during hospital stays, were independently associated with increased odds ratio of mortality.

STARD-compliant article: The utility of red cell distribution width to predict mortality for septic patients visiting the emergency department.

Sepsis is a common condition in the emergency department that is associated with high mortality. Red blood cell distribution width (RDW) has been used as a simple prognosis predictor for patients with community-acquired pneumonia, gram-negative bacteremia, and severe sepsis or septic shock. To evaluate the performance of RDW to predict in-hospital mortality among septic patients, we conducted a hospital-based retrospective cohort study in an emergency department of a tertiary teaching hospital. RDW was compared with other commonly used clinical prediction scores (Systemic Inflammatory Response Syndrome (SIRS), Mortality in Emergency Department Sepsis (MEDS) and the Confusion, Urea nitrogen, Respiratory rate, Blood pressure, 65 years of age and older (CURB65)). Of 6973 consecutive adult patients with a clinical diagnosis of sepsis and 2 sets of blood culture ordered by physicians, 477 (6.8%) died. The mortality group had higher RDW levels than the survival group (15.7% vs 13.8%). After dividing RDW into quartiles, the patients in the highest RDW quartile (RDW >15.6%; mortality, 16.7%) had more than twice the risk of in-hospital mortality compared with patients in the second highest quartile (RDW >14% and <15.6%; mortality, 7.3%), whereas the mortality rate in the lowest RDW quartile (<13.1%) was only 1.6%. The area under the receiver operating characteristic curve of RDW to predict mortality was 0.75 (95% confidence interval, 0.72-0.77), which is significantly higher than the areas under the curve of clinical prediction rules (SIRS, MEDS, and CURB65). After integrating RDW into these scores, all scores performed better in predicting mortality (0.73, 0.72, and 0.77, for SIRS, MEDS, and CURB65, respectively). RDW could be an independent predictor of mortality among septic patients. Clinicians could classify the septic patients into different risk groups according to RDW quartiles. For more accurate mortality prediction, RDW could be a potential parameter to be incorporated into clinical prediction rules.

Does procalcitonin, C-reactive protein, or interleukin-6 test have a role in the diagnosis of severe infection in patients with febrile neutropenia? A systematic review and meta-analysis.

PURPOSE: The study aims to determine the usefulness of procalcitonin (PCT) and other blood markers for identification of bacterial infection among patients with febrile neutropenia (FN). METHODS: The Medline, EMBASE, and Cochrane databases were searched for articles from 1966 to December 2012. We performed a search to identify articles that examined the diagnostic accuracy of PCT in patients with FN. Statistical analyses (fixed- or random-effect models) were conducted to summarize and calculate the sensitivity, specificity, likelihood ratios, and 95 % confidence intervals (CIs). RESULTS: Twenty-seven studies were included (1960 febrile episodes) for PCT analysis, 13 (1712 febrile episodes) for C-reactive protein (CRP) analysis, and five (314 febrile episodes) for interleukin (IL)-6 analysis. Increased PCT levels (odds ratio [OR] 11.5; 95 % CI 7.6 to 17.3), raised CRP levels (3.3; 2.7 to 4.2), and raised IL-6 levels (10.0; 5.5 to 18.0) were significantly associated with bacterial infection. Overall positive likelihood ratio was 5.49 (4.04-7.45) for PCT, 1.82 (1.42-2.33) for CRP, and 3.68 (2.41-5.60) for IL-6. Overall negative likelihood ratio was 0.40 (0.31-0.51) for PCT, 0.40 (0.26-0.61) for CRP, and 0.33 (0.23-0.46) for IL-6. CONCLUSIONS: Of the three potentially useful markers, PCT had the best positive likelihood ratio and can be used to confirm the diagnosis of bacterial infections in patients with FN. Due to unacceptably high negative likelihood ratio, medical decision for stopping antibiotics based on PCT alone in this high-risk population may not be possible.

Role of procalcitonin in the diagnosis of infective endocarditis: a meta-analysis.

BACKGROUND: Infective endocarditis (IE) is a diagnostic challenge. We aimed to systemically summarize the current evidence on the diagnostic value of procalcitonin (PCT) in identifying IE. METHODS: We searched EMBASE, MEDLINE, Cochrane database, and reference lists of relevant articles with no language restrictions through September 2012 and selected studies that reported the diagnostic performance of PCT alone or compare with other biomarkers to diagnose IE. We summarized test performance characteristics with the use of forest plots, hierarchical summary receiver operating characteristic curves, and bivariate random effects models. RESULTS: We found 6 qualifying studies that included 1006 episodes of suspected infection with 216 (21.5%) confirmed IE episodes from 5 countries. Bivariate pooled sensitivity, specificity, positive likelihood ratios, and negative likelihood ratios were 64% (95% confidence interval [CI], 52%-74%), 73% (95% CI 58%-84%), 2.35 (95% CI 1.40-3.95), and 0.50 (95% CI 0.35-0.70), respectively. Of the 5 studies examining C-reactive protein (CRP), the pooled sensitivity, specificity, positive likelihood ratios, and negative likelihood ratios were 75% (95% CI 62%-85%), 73% (95% CI 61%-82%), 2.81 (95% CI 1.70-4.65), and 0.34 (95% CI 0.19-0.60), respectively. The global measures of accuracy, area under the receiver operating characteristic curve (AUC) and diagnostic odds ratio (dOR), showed CRP (AUC 0.80, dOR 8.55) may have higher accuracy than PCT (AUC 0.71, dOR 4.67) in diagnosing IE. CONCLUSIONS: Current evidence does not support the routine use of serum PCT or CRP to rule in or rule out IE in patients suspected to have IE.