Background:

The treatment of people with pancreatic necrosis differs from that of people with oedematous pancreatitis. It is important to know the diagnostic accuracy of serum C-reactive protein (CRP), serum procalcitonin, and serum lactate dehydrogenase (LDH) as a triage test for the detection of pancreatic necrosis in people with acute pancreatitis, so that an informed decision can be made as to whether the person with pancreatic necrosis needs further investigations such as computed tomography (CT) scan or magnetic resonance imaging (MRI) scan and treatment for pancreatic necrosis started. There is currently no standard clinical practice, although CRP, particularly an increasing trend of CRP, is often used as a triage test to determine whether the person requires further imaging. There is also currently no systematic review of the diagnostic test accuracy of CRP, procalcitonin, and LDH for the diagnosis of pancreatic necrosis in people with acute pancreatitis.
Objectives:

To compare the diagnostic accuracy of CRP, procalcitonin, or LDH (index test), either alone or in combination, in the diagnosis of necrotising pancreatitis in people with acute pancreatitis and without organ failure.
Search methods

We searched MEDLINE, Embase, Science Citation Index Expanded, National Institute for Health Research (NIHR HTA and DARE), and other databases until March 2017. We searched the references of the included studies to identify additional studies. We did not restrict studies based on language or publication status, or whether data were collected prospectively or retrospectively. We also performed a 'related search' and 'citing reference' search in MEDLINE and Embase.
Selection criteria:

We included all studies that evaluated the diagnostic test accuracy of CRP, procalcitonin, and LDH for the diagnosis of pancreatic necrosis in people with acute pancreatitis using the following reference standards, either alone or in combination: radiological features of pancreatic necrosis (contrast-enhanced CT or MRI), surgeon's judgement of pancreatic necrosis during surgery, or histological confirmation of pancreatic necrosis. Had we found case-control studies, we planned to exclude them because they are prone to bias; however, we did not locate any. Two review authors independently identified the relevant studies from the retrieved references.
Data collection and analysis:

Two review authors independently extracted data, including methodological quality assessment, from the included studies. As the included studies reported CRP, procalcitonin, and LDH on different days of admission and measured at different cut-off levels, it was not possible to perform a meta-analysis using the bivariate model as planned. We have reported the sensitivity, specificity, post-test probability of a positive and negative index test along with 95% confidence interval (CI) on each of the different days of admission and measured at different cut-off levels.
Main results:

A total of three studies including 242 participants met the inclusion criteria for this review. One study reported the diagnostic performance of CRP for two threshold levels (> 200 mg/L and > 279 mg/L) without stating the day on which the CRP was measured. One study reported the diagnostic performance of procalcitonin on day 1 (1 day after admission) using a threshold level of 0.5 ng/mL. One study reported the diagnostic performance of CRP on day 3 (3 days after admission) using a threshold level of 140 mg/L and LDH on day 5 (5 days after admission) using a threshold level of 290 U/L. The sensitivities and specificities varied: the point estimate of the sensitivities ranged from 0.72 to 0.88, while the point estimate of the specificities ranged from 0.75 to 1.00 for the different index tests on different days of hospital admission. However, the confidence intervals were wide: confidence intervals of sensitivities ranged from 0.51 to 0.97, while those of specificities ranged from 0.18 to 1.00 for the different tests on different days of hospital admission. Overall, none of the tests assessed in this review were sufficiently accurate to suggest that they could be useful in clinical practice.
Authors' conclusions:

The paucity of data and methodological deficiencies in the studies meant that it was not possible to arrive at any conclusions regarding the diagnostic test accuracy of the index test because of the uncertainty of the results. Further well-designed diagnostic test accuracy studies with prespecified index test thresholds of CRP, procalcitonin, LDH; appropriate follow-up (for at least two weeks to ensure that the person does not have pancreatic necrosis, as early scans may not indicate pancreatic necrosis); and clearly defined reference standards (of surgical or radiological confirmation of pancreatic necrosis) are important to reliably determine the diagnostic accuracy of CRP, procalcitonin, and LDH.

Serum C‐reactive protein, procalcitonin, and lactate dehydrogenase for the diagnosis of pancreatic necrosis

Therapeutic cancer vaccines targeting melanoma-associated antigens are commonly immunogenic but are rarely effective in promoting objective clinical responses. To identify critical molecules for activation of effective antitumor immunity, we have profiled autologous dendritic cell (DC) vaccines used to treat 35 patients with melanoma. We showed that checkpoint molecules induced by ex vivo maturation correlated with in vivo DC vaccine activity. Melanoma patient DCs had reduced expression of cell surface inducible T-cell costimulator ligand (ICOSL) and had defective intrinsic NF-κB signaling. Chromatin immunoprecipitation assays revealed NF-κB-dependent transcriptional regulation of ICOSL expression by DCs. Blockade of ICOSL on DCs reduced priming of antigen-specific CD8+ and CD4+ T cells from naive donors in vitro Concentration of extracellular/soluble ICOSL released from vaccine DCs positively correlated with patient clinical outcomes, which we showed to be partially regulated by ADAM10/17 sheddase activity. These data point to the critical role of canonical NF-κB signaling, the regulation of matrix metalloproteinases, and DC-derived ICOSL in the specific priming of cognate T-cell responses in the cancer setting. This study supports the implementation of targeted strategies to augment these pathways for improved immunotherapeutic outcomes in patients with cancer.

/pdf/dysregulated-nf-kb-dependent-icosl-expression-in-human-i1pbfdx05i.pdf

Dysregulated NF-κB-Dependent ICOSL Expression in Human Dendritic Cell Vaccines Impairs T-cell Responses in Patients with Melanoma.

The early diagnosis and severity grading for acute pancreatitis (AP) are difficult to determine because of the complexity and differences in disease process. To date, few studies have investigated the role of lymphocyte ratio (LR) in AP. Therefore, the objective of the present study was to investigate the prognostic value of LR as an indicator in AP, as well as determine an optimal cut-off value for the severity prediction. There were two hundred four patients involved in this study, ninety-two of whom had severe acute pancreatitis (SAP). The LR was analyzed on admission and correlated with severity, which was determined using the Atlanta classification. The optimal cut-off value for LR was generated using receiving operator characteristic (ROC) curves. The results showed that the LR in the SAP group decreased significantly compared to the mild acute pancreatitis (MAP) group (8.82 vs. 13.43). The optimal cut-off value obtained from ROC curves was 0.081, with a sensitivity of 80.4%, a specificity of 53.3%, a positive likelihood ratio of 1.722, and a negative likelihood ratio of 0.368. In conclusion, the LR is obviously related to the condition of AP patients and is valuable for the differential diagnosis of SAP in early stages of AP.

/pdf/a-reduced-lymphocyte-ratio-as-an-early-marker-for-predicting-2j5omojh8n.pdf

A reduced lymphocyte ratio as an early marker for predicting acute pancreatitis.

Dysregulated B7H4/JAK2/STAT3 Pathway Involves in Hypertriglyceridemia Acute Pancreatitis and Is Attenuated by Baicalin

As an important ligand in T lymphocyte costimulatory pathways, B7-H5 is involved deeply in the immune response in various diseases. However, its clinical usefulness as an early indicator in acute pancreatitis (AP) remains unclear. In this study, the levels of sB7-H5 and cytokines in plasma samples of 75 AP patients, 20 abdominal pain patients without AP, and 20 healthy volunteers were determined. Then, the correlation of sB7-H5 and clinical features, cytokines, the Ranson score, APACHE II score, Marshall score, and BISAP score was analysed, and the value of sB7-H5 for diagnostic, severity, and prognosis of AP was evaluated. We found that the levels of sB7-H5 were specifically upregulated in AP patients. Receiver operating characteristic (ROC) analysis revealed that sB7-H5 can identify AP patients from healthy or abdominal pain patients with 78.9% or 86.4% sensitivity and 93.3% or 90.0% specificity. Further analysis showed that the levels of sB7-H5 were significantly correlated with WBC (p = 0.004), GLU (p = 0.008), LDH (p < 0.001), Ca2+ (p = 0.006), AST (p = 0.009), PLT (p = 0.041), IL-6 (p < 0.001), IL-10 (p < 0.001), and TNF-α (p < 0.001). And levels of sB7-H5 were gradually increased among patients with mildly acute pancreatitis (MAP), moderately severe acute pancreatitis (MSAP), and severe acute pancreatitis (SAP). It can distinguish the severity of AP with good sensitivity and specificity. Moreover, when dividing the patients into two groups according to the median level of sB7-H5, the local complication and length of stay of low levels of the sB7-H5 group were significantly less than those in high levels of the sB7-H5 group. And the levels of sB7-H5 in AP patients were significantly correlated with the Ranson score (p < 0.001), APACHE II score (p < 0.001), Marshall score (p < 0.001), and BISAP score (p < 0.001). The AUCs of assessing local complications of sB7-H5 at day 1 and day 3 were 0.704 (p = 0.0024) and 0.727 (p = 0.0373). These results showed the potential value of sB7-H5 as a diagnostic, severity, and prognosis marker of AP.

/pdf/soluble-b7-h5-is-a-novel-diagnostic-severity-and-prognosis-36suxn9qyi.pdf

Soluble B7-H5 Is a Novel Diagnostic, Severity, and Prognosis Marker in Acute Pancreatitis.

The clinical usefulness of soluble B7-H2 (sB7-H2) as an early indicator of acute pancreatitis (AP) remains unclear, so we performed the present study to investigate this issue. For our cohort, we recruited 75 patients with AP, 70 patients with other abdominal sepsis, and 20 healthy control individuals. The sB7-H2 levels of AP patients or healthy control individuals were measured by enzyme-linked immunosorbent assay (ELISA). The sB7-H2 levels in patients with AP rather than other patients with abdominal sepsis were significantly higher than those in healthy controls. Hence, we selected AP to study the clinical significance of sB7-H2 in inflammatory conditions. The sB7-H2 level was positively correlated with the white blood cell (WBC) count and the lactate dehydrogenase (LDH), high-sensitivity C-reactive protein (hs-CRP), and lipopolysaccharide LPS levels (P <.05 for each). Receiver operating characteristic (ROC) analysis revealed that sB7-H2 can distinguish moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP) from mildly acute pancreatitis (MAP) with 77.8% sensitivity and 80.0% specificity; and that the levels of sB7-H2 also can distinguish SAP from MSAP and MAP with 92.0% sensitivity and 86.0% specificity. The present results indicate that sB7-H2 might be a useful marker in the clinical diagnosis of AP.

Soluble B7-H2 as a novel marker in early evaluation of the severity of acute pancreatitis.

Objective
To explore the clinical significance of B7 family homology factor-3 (B7-H3), an expression membrane type of myeloid-derived suppressor cell (MDSC), in patients with acute pancreatitis (AP).


Methods
A total of 63 patients with AP initially treated in the Emergency Department at the First Affiliated Hospital of Soochow University from January, 2014 to December, 2015 were selected.Of them, 25 suffered from mild AP (MAP), 20 had moderate AP (MSAP) and 18 had severe AP (SAP). Another 20 healthy subjects with matching age and gender served as the control group. All patients with AP conformed to the diagnostic criteria of Guidelines or Diagnosis and Treatment of Acute Pancreatitis set in 2013 in China. Patients with other underlying diseases that might influence the clinical outcomes were excluded, including those with tumors, autoimmune diseases, viral infections, trauma and other disorders. A flowcytometer was used to detect the expression rate of MDSC in peripheral venous blood and the expression of B7-H3 on MDSC membrane. The continuous monitoring was carried out for 24 h, 48 h and 72 h in patients with AP.


Results
Compared with healthy subjects, the MDSC cells in patient groups 24 hours after AP onset increased notably(P<0.01)especially the highest increase in the SAP group, followed by the MSAP group and the lowest in the MAP group. There were significant differences in pairwise comparisons(P<0.05). From successive observation of each group, there was no significant difference in MDSC between the MAP group and the MSAP group 24 hours, 48 hours and 72 hours after AP onset. However, MDSC reached its peak 48 hours after AP onset, but it declined 72 hours after AP onset in the SAP group(P<0.05). B7-H3 expressed significantly 24 hours after AP onset, but there was no expression of B7-H3 in the healthy group. Meanwhile, B7-H3 was expressed most highly in the SAP group, followed by the MSAP group and lowest in the MAP group. There were significant differences in expression of B7-H3 found in pairwise comparisons(P<0.05). The successive observation showed that there was no significant difference in B7-H3 expression between the MAP group and the MSAP group 24 hours, 48 hours and 72 hours after AP onset. However, there was a trend of increase in B7-H3 expression as time prolonged found among 24 hours, 48 hours and 72 hours after AP onset in the SAP group (P<0.05).


Conclusions
The expressions of MDSC and B7-H3 were high in AP, and there were significant differences in both expressions among MAP, MSAP and SAP groups. These phenomena offer clues in further understanding about the immunological disorders during AP giving better guidelines for clinical practice.


Key words: 
Acute pancreatitis; Myeloid-derived suppressor cell; B7 family homology factor-3

Jiaqing Shen

Papers

Soluble B7-H2 as a novel marker in early evaluation of the severity of acute pancreatitis.

Clinical significance of B7-H3, an expression membrane type of myeloid-derived suppressor cell in patients with acute pancreatitis