Spermine oxidase regulates liver inflammation and fibrosis through ß-catenin pathway.

BACKGROUND: Spermine oxidase (SMOX), an inducible enzyme involved in the catabolic pathway of polyamine, was found to be upregulated in hepatocellular carcinoma and might be an important oncogene of it in our previous studies. This study attempted to further investigate its relationship with liver inflammation and fibrosis both in vitro and in vivo. METHODS: The effect of SMOX inhibition on LPS-induced inflammatory response in mouse liver cell line AML12 was validated by using small interfering RNA or SMOX inhibitor MDL72527. Western blotting and immunofluorescence were utilized to verify whether LPS could induce ß-catenin to transfer into the nucleus and whether it could be reversed by interfering with the expression of SMOX or using SMOX inhibitor. Then, the SMOX inhibitor MDL72527 and SMOX knockout mice were used to verify the hypothesis above in vivo. RESULTS: The expression of SMOX could be induced by LPS in AML12 cells. The inhibition of SMOX could inhibit LPS-induced inflammatory response in AML12 cells. LPS could induce ß-catenin transfer from cytoplasm to nucleus, while SMOX downregulation or inhibition could partially reverse this process. In vivo intervention with SMOX inhibitor MDL72527 or SMOX knockout mice could significantly improve the damage of liver function, reduce intrahepatic inflammation, inhibit the nuclear transfer of ß-catenin in liver tissue, and alleviate carbon tetrachloride-induced liver fibrosis in mice. CONCLUSION: SMOX can promote the inflammatory response and fibrosis of hepatocytes. It provides a new therapeutic strategy for hepatitis and liver fibrosis, inhibiting early liver cancer.

The role of mitochondrial damage-associated molecular patterns in acute pancreatitis.

Acute pancreatitis (AP) is one of the most common gastrointestinal tract diseases with significant morbidity and mortality. Current treatments remain unspecific and supportive due to the severity and clinical course of AP, which can fluctuate rapidly and unpredictably. Mitochondria, cellular power plant to produce energy, are involved in a variety of physiological or pathological activities in human body. There is a growing evidence indicating that mitochondria damage-associated molecular patterns (mtDAMPs) play an important role in pathogenesis and progression of AP. With the pro-inflammatory properties, released mtDAMPs may damage pancreatic cells by binding with receptors, activating downstream molecules and releasing inflammatory factors. This review focuses on the possible interaction between AP and mtDAMPs, which include cytochrome c (Cyt c), mitochondrial transcription factor A (TFAM), mitochondrial DNA (mtDNA), cardiolipin (CL), adenosine triphosphate (ATP) and succinate, with focus on experimental research and potential therapeutic targets in clinical practice. Preventing or diminishing the release of mtDAMPs or targeting the mtDAMPs receptors might have a role in AP progression.

Comparison of an interpretable extreme gradient boosting model and an artificial neural network model for prediction of severe acute pancreatitis.

INTRODUCTION: Acute pancreatitis (AP) that progresses to persistent organ failure is referred to as severe acute pancreatitis (SAP). It is a condition associated with a relatively high mortality. A prediction model that would facilitate early recognition of patients at risk for SAP is crucial for improvement of patient prognosis. OBJECTIVES: The aim of this study was to evaluate the accuracy of extreme gradient boosting (XGBoost) and artificial neural network (ANN) models for predicting SAP. PATIENTS AND METHODS: A total of 648 patients with AP were enrolled. XGBoost and ANN models were developed and validated in the training (519 patients) and test sets (129 patients). The accuracy and predictive performance of the XGBoost and ANN models were evaluated using both the area under the receiver operating characteristic curves (AUCs) and the area under the precision­recall curves (AUC­PRs). RESULTS: A total of 15 variables were selected for model construction through a univariable analysis. The AUCs of the XGBoost and ANN models in 5­fold cross­validation of the training set were 0.92 (95% CI, 0.87-0.97) and 0.86 (95% CI, 0.78-0.92), respectively, whereas the AUCs for the test set were 0.93 (95% CI, 0.85-1) and 0.87 (95% CI, 0.79-0.96), respectively. The XGBoost model outperformed the ANN model in terms of both diagnostic accuracy and AUC­PR. Individual predictions of the XGBoost model were explained using a local interpretable model­agnostic explanation plot. CONCLUSIONS: An interpretable XGBoost model showed better discriminatory efficiency for predicting SAP than the ANN model, and could be used in clinical practice to identify patients at risk for SAP.

Comprehensive review on the pathogenesis of hypertriglyceridaemia-associated acute pancreatitis.

It is well known, that the inflammatory process that characterizes acute pancreatitis (AP) can lead to both pancreatic damage and systemic inflammatory response syndrome (SIRS). During the last 20 years, there has been a growing incidence of episodes of acute pancreatitis associated with hypertriglyceridaemia (HTAP). This review provides an overview of triglyceride metabolism and the potential mechanisms that may contribute to developing or exacerbating HTAP. The article comprehensively discusses the various pathological roles of free fatty acid, inflammatory response mechanisms, the involvement of microcirculation, serum calcium overload, oxidative stress and the endoplasmic reticulum, genetic polymorphism, and gut microbiota, which are known to trigger or escalate this condition. Future perspectives on HTAP appear promising, with ongoing research focused on developing more specific and effective treatment strategies.

Relationship between Cholesterol-Related Lipids and Severe Acute Pancreatitis: From Bench to Bedside.

It is well known that hypercholesterolemia in the body has pro-inflammatory effects through the formation of inflammasomes and augmentation of TLR (Toll-like receptor) signaling, which gives rise to cardiovascular disease and neurodegenerative diseases. However, the interaction between cholesterol-related lipids and acute pancreatitis (AP) has not yet been summarized before. This hinders the consensus on the existence and clinical importance of cholesterol-associated AP. This review focuses on the possible interaction between AP and cholesterol-related lipids, which include total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and apolipoprotein (Apo) A1, from the bench to the bedside. With a higher serum level of total cholesterol, LDL-C is associated with the severity of AP, while the persistent inflammation of AP is allied with a decrease in serum levels of cholesterol-related lipids. Therefore, an interaction between cholesterol-related lipids and AP is postulated. Cholesterol-related lipids should be recommended as risk factors and early predictors for measuring the severity of AP. Cholesterol-lowering drugs may play a role in the treatment and prevention of AP with hypercholesterolemia.

Fabp5 is a common gene between a high-cholesterol diet and acute pancreatitis.

Background and aims: Hypercholesterolemia has been identified as risk factor for severe acute pancreatitis (AP). We aimed to identify the common differentially expressed genes (DEGs) between a high-cholesterol diet and AP. Methods: We retrived gene expression profiles from the GEO database. DEGs were assessed using GEO2R. For AP hub genes, we conducted functional enrichment analysis and protein-protein interaction (PPI) analysis. GeneMANIA and correlation analysis were employed to predict potential DEG mechanisms. Validation was done across various healthy human tissues, pancreatic adenocarcinoma, peripheral blood in AP patients, and Sprague-Dawley rats with AP. Results: The gene "Fabp5" emerged as the sole common DEG shared by a high-cholesterol diet and AP. Using the 12 topological analysis methods in PPI network analysis, Rela, Actb, Cdh1, and Vcl were identified as hub DEGs. GeneMANIA revealed 77.6% physical interactions among Fabp5, TLR4, and Rela, while genetic correlation analysis indicated moderate associations among them. Peripheral blood analysis yielded area under the ROC curve (AUC) values of 0.71, 0.63, 0.74, 0.64, and 0.91 for Fabp5, TLR4, Actb, Cdh1 genes, and artificial neural network (ANN) model respectively, in predicting severe AP. In vivo immunohistochemical analysis demonstrated higher Fabp5 expression in the hyperlipidemia-associated AP group compared to the AP and control groups. Conclusion: Fabp5 emerged as the common DEG connecting a high-cholesterol diet and AP. Rela was highlighted as a crucial hub gene in AP. Genetic interactions were observed among Fabp5, TLR4, and Rela. An ANN model consisting of Fabp5, TLR4, Actb, and Cdh1 was helpful in predicting severe AP.

Non-linear correlation between amylase day 2 to day 1 ratio and incidence of severe acute pancreatitis.

Background: This study aimed to assess whether the amylase day 2/amylase day 1 ratio was associated with severe acute pancreatitis (SAP). Methods: We retrospectively enrolled 464 patients with acute pancreatitis. Serum amylase was measured on admission (day 1) and 24 h later (day 2). Univariable logistic regression with restricted cubic spline analysis, multivariable logistic analysis, and receiver operating characteristic curve analysis was used to evaluate the relationship between the amylase day 2/amylase day 1 ratio and SAP. Results: A non-linear association between the amylase day 2/amylase day 1 ratio and SAP was observed. The multivariable logistic analysis confirmed that a high amylase day 2/amylase day 1 ratio (≥0.3) was independently associated with the development of SAP (OR: 6.62). The area under the receiver operating characteristic curve (AUC) of the amylase day 2/amylase day 1 ratio, as a predictive factor for SAP, was 0.65. When amylase ratio ≥0.3 was counted as 1 point and added to the BISAP score to build a new model named the BISAPA (BISAP plus Amylase ratio) score (AUC = 0.86), it improved the diagnostic power of the original BISAP score (AUC = 0.83) for SAP. With a cut-off value of 3, the BISAPA score achieved a sensitivity of 66.0%, a specificity of 86.7%, and diagnostic accuracy of 84.48%. Conclusions: There is a non-linear correlation between the amylase day 2/amylase day 1 ratio and the incidence of SAP. BISAPA score might also be a useful tool for the same purpose.

Nomogram of intra-abdominal infection after surgery in patients with gastric cancer: A retrospective study.

Background: Surgical resection is still the primary way to treat gastric cancer. Therefore, postoperative complications such as IAI (intra-abdominal infection) are major problems that front-line clinical workers should pay special attention to. This article was to build and validate IAI's RF (regression function) model. Furthermore, it analyzed the prognosis in patients with IAI after surgery for stomach cancer. The above two points are our advantages, which were not involved in previous studies. Methods: The data of this study was divided into two parts, the training data set and the validation data set. The training data for this article were from the patients treated surgically with gastric cancer in our center from December 2015 to February 2017. We examined IAI's morbidity, etiological characteristics, and prognosis in the training data set. Univariate and multivariate logistic regression analyses were used to screen risk factors, establish an RF model and create a nomogram. Data from January to March 2021 were used to validate the accuracy of the RF model. Results: The incidence of IAI was 7.2%. The independent risk factors for IAI were hypertension (Odds Ratio [OR] = 3.408, P = 0.001), history of abdominal surgery (OR = 2.609, P = 0.041), combined organ excision (OR = 4.123, P = 0.010), and operation time ≥240 min (OR = 3.091, P = 0.005). In the training data set and validation data set, the area under the ROC curve of IAI predicted by the RF model was 0.745 ± 0.048 (P<0.001) and 0.736 ± 0.069 (P=0.003), respectively. In addition, IAI significantly extended the length of hospital stay but had little impact on survival. Conclusions: Patients with hypertension, combined organ excision, a history of abdominal surgery, and a surgical duration of 240 min or more are prone to IAI, and the RF model may help to identify them.

Evaluation of the risk factors for severe complications and surgery of intestinal foreign bodies in adults: a single-center experience with 180 cases.

Background: Foreign bodies (FBs) lodged in the intestine or causing intestinal complications are uncommon in clinical practice but may pose diagnostic difficulties and prove life-threatening. This study aimed to evaluate the risk factors for severe complications and surgery to aid clinicians in the diagnosis and management of intestinal FBs. Methods: We performed a retrospective analysis of patients in whom FBs were lodged in the intestine or caused complications from 2010 to 2020 in the First Affiliated Hospital of Wenzhou Medical University (Zhejiang, China). The characteristics of the patients and FBs, symptoms, imaging findings, diagnostics, treatment strategies, and clinical outcomes were analysed. Furthermore, the risk factors for complications and surgery were investigated. Results: In total, 180 patients were included in our study. Most patients (76.1%) were unable to provide a history of ingestion. Bezoars were the most common FBs (35.6%). The FBs were mainly located in the duodenum (32.8%) and the ileum (27.8%). Surgical removal of FBs was successful in 89 (49.4%) patients and endoscopic removal in 54 (30.0%) patients. Eleven with perforations were treated conservatively. FBs located in the jejunum or ileum were more likely to cause severe complications than those located in the duodenum. FBs located in the jejunum, ileum, or sigmoid colon were more likely to undergo surgery, and severe complications were an independent risk factor for surgery. Conclusion: Intestinal FBs, often localized in angulation, are likely to be misdiagnosed because most patients do not provide a history of FB ingestion. Surgery and endoscopic therapy are the most commonly used treatment modalities. Surgery is not mandatory in clinically stable patients with small and contained perforations. FBs located in the jejunum or ileum are risk factors for both complications and surgery.

Damage associated molecular patterns and neutrophil extracellular traps in acute pancreatitis.

Previous researches have emphasized a trypsin-centered theory of acute pancreatitis (AP) for more than a century. With additional studies into the pathogenesis of AP, new mechanisms have been explored. Among them, the role of immune response bears great importance. Pro-inflammatory substances, especially damage-associated molecular patterns (DAMPs), play an essential role in activating, signaling, and steering inflammation. Meanwhile, activated neutrophils attach great importance to the immune defense by forming neutrophil extracellular traps (NETs), which cause ductal obstruction, premature trypsinogen activation, and modulate inflammation. In this review, we discuss the latest advances in understanding the pathological role of DAMPs and NETs in AP and shed light on the flexible crosstalk between these vital inflammatory mediators. We, then highlight the potentially promising treatment for AP targeting DAMPs and NETs, with a focus on novel insights into the mechanism, diagnosis, and management of AP.

Usefulness of Random Forest Algorithm in Predicting Severe Acute Pancreatitis.

Background and Aims: This study aimed to develop an interpretable random forest model for predicting severe acute pancreatitis (SAP). Methods: Clinical and laboratory data of 648 patients with acute pancreatitis were retrospectively reviewed and randomly assigned to the training set and test set in a 3:1 ratio. Univariate analysis was used to select candidate predictors for the SAP. Random forest (RF) and logistic regression (LR) models were developed on the training sample. The prediction models were then applied to the test sample. The performance of the risk models was measured by calculating the area under the receiver operating characteristic (ROC) curves (AUC) and area under precision recall curve. We provide visualized interpretation by using local interpretable model-agnostic explanations (LIME). Results: The LR model was developed to predict SAP as the following function: -1.10-0.13×albumin (g/L) + 0.016 × serum creatinine (µmol/L) + 0.14 × glucose (mmol/L) + 1.63 × pleural effusion (0/1)(No/Yes). The coefficients of this formula were utilized to build a nomogram. The RF model consists of 16 variables identified by univariate analysis. It was developed and validated by a tenfold cross-validation on the training sample. Variables importance analysis suggested that blood urea nitrogen, serum creatinine, albumin, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, calcium, and glucose were the most important seven predictors of SAP. The AUCs of RF model in tenfold cross-validation of the training set and the test set was 0.89 and 0.96, respectively. Both the area under precision recall curve and the diagnostic accuracy of the RF model were higher than that of both the LR model and the BISAP score. LIME plots were used to explain individualized prediction of the RF model. Conclusions: An interpretable RF model exhibited the highest discriminatory performance in predicting SAP. Interpretation with LIME plots could be useful for individualized prediction in a clinical setting. A nomogram consisting of albumin, serum creatinine, glucose, and pleural effusion was useful for prediction of SAP.

Hyperlipemia pancreatitis onset time affects the association between elevated serum triglyceride levels and disease severity.

BACKGROUND: The association of serum triglyceride (TG) levels with the severity of hypertriglyceridaemia-induced acute pancreatitis (HTG-AP) remains controversial. This study aimed to comprehensively assess the TG levels from the initial onset and their predictive value in the disease assessment of HTG-AP. METHODS: Data collected from January 2018 to July 2021 in one institute were assessed retrospectively. HTG-AP was defined as a TG level > 500 mg/dL in the absence of other common aetiologies of AP. The TG levels within 24 hours (24 h), 48 hours (48 h), 3-4 days (3-4 d), and 5-7 days (5-7 d) after symptom onset and their correlations with disease severity in HTG-AP patients were analysed by cross-sectional and longitudinal studies. RESULTS: In the cross-sectional study, 377 HTG-AP patients were included before lipid-lowering intervention: 216 subjects had their first TG levels measured within 24 h after onset, 91 within 48 h, 50 in 3-4 d, and 20 in 5-7 d. TG levels decreased in the 24 h, 48 h and 3-4 d groups (P < 0.001), however, the TG decline in the 5-7 d group had no difference compared with the 3-4 d group. HTG-AP patients with severe or moderately severe disease displayed higher TG levels than those with mild disease in the 24 h and 48 h groups (P < 0.050) but not in the 3-4 d or 5-7 d groups. Furthermore, the TG levels were correlated with the modified computed tomography severity index only in the 24 h and 48 h groups, while an association between serum calcium levels and C-reactive protein levels was only present in the 24 h group. Similarly, the TG levels were related to hospital days and ICU days in the 24 h and/or 48 h groups. In the longitudinal study, 165 patients with complete records of TG levels from 24 h to 5-7 d were enrolled. With supportive care and lipid-lowering treatment after admission, the TG levels declined rapidly (P < 0.001), and the correlations with disease severity weakened or even disappeared from 24 h to 5-7 d. CONCLUSION: TG levels decreased and attenuated the association with disease severity of HTG-AP over the time of onset. The TG levels within the initial 48 h after onset were most useful for the diagnosis and disease assessment of HTG-AP.

A Comparison of XGBoost, Random Forest, and Nomograph for the Prediction of Disease Severity in Patients With COVID-19 Pneumonia: Implications of Cytokine and Immune Cell Profile.

Background and Aims: The aim of this study was to apply machine learning models and a nomogram to differentiate critically ill from non-critically ill COVID-19 pneumonia patients. Methods: Clinical symptoms and signs, laboratory parameters, cytokine profile, and immune cellular data of 63 COVID-19 pneumonia patients were retrospectively reviewed. Outcomes were followed up until Mar 12, 2020. A logistic regression function (LR model), Random Forest, and XGBoost models were developed. The performance of these models was measured by area under receiver operating characteristic curve (AUC) analysis. Results: Univariate analysis revealed that there was a difference between critically and non-critically ill patients with respect to levels of interleukin-6, interleukin-10, T cells, CD4+ T, and CD8+ T cells. Interleukin-10 with an AUC of 0.86 was most useful predictor of critically ill patients with COVID-19 pneumonia. Ten variables (respiratory rate, neutrophil counts, aspartate transaminase, albumin, serum procalcitonin, D-dimer and B-type natriuretic peptide, CD4+ T cells, interleukin-6 and interleukin-10) were used as candidate predictors for LR model, Random Forest (RF) and XGBoost model application. The coefficients from LR model were utilized to build a nomogram. RF and XGBoost methods suggested that Interleukin-10 and interleukin-6 were the most important variables for severity of illness prediction. The mean AUC for LR, RF, and XGBoost model were 0.91, 0.89, and 0.93 respectively (in two-fold cross-validation). Individualized prediction by XGBoost model was explained by local interpretable model-agnostic explanations (LIME) plot. Conclusions: XGBoost exhibited the highest discriminatory performance for prediction of critically ill patients with COVID-19 pneumonia. It is inferred that the nomogram and visualized interpretation with LIME plot could be useful in the clinical setting. Additionally, interleukin-10 could serve as a useful predictor of critically ill patients with COVID-19 pneumonia.

The function of specialized pro-resolving endogenous lipid mediators, vitamins, and other micronutrients in the control of the inflammatory processes: Possible role in patients with SARS-CoV-2 related infection.

Inflammation is an essential protective response against harmful stimuli, such as invading pathogens, damaged cells, or irritants. Physiological inflammation eliminates pathogens and promotes tissue repair and healing. Effective immune response in humans depends on a tightly regulated balance among inflammatory and anti-inflammatory mechanisms involving both innate and adaptive arms of the immune system. Excessive inflammation can become pathological and induce detrimental effects. If this process is not self-limited, an inappropriate remodeling of the tissues and organs can occur and lead to the onset of chronic degenerative diseases. A wide spectrum of infectious and non-infectious agents may activate the inflammation, via the release of mediators and cytokines by distinct subtypes of lymphocytes and macrophages. Several molecular mechanisms regulate the onset, progression, and resolution of inflammation. All these steps, even the termination of this process, are active and not passive events. In particular, a complex interplay exists between mediators (belonging to the group of Eicosanoids), which induce the beginning of inflammation, such as Prostaglandins (PGE2), Leukotrienes (LT), and thromboxane A2 (TXA2), and molecules which display a key role in counteracting this process and in promoting its proper resolution. The latter group of mediators includes: ω-6 arachidonic acid (AA)-derived metabolites, such as Lipoxins (LXs), ω -3 eicosapentaenoic acid (EPA)-derived mediators, such as E-series Resolvins (RvEs), and ω -3 docosahexaenoic (DHA)-derived mediators, such as D-series Resolvins (RvDs), Protectins (PDs) and Maresins (MaRs). Overall, these mediators are defined as specialized pro-resolving mediators (SPMs). Reduced synthesis of these molecules may lead to uncontrolled inflammation with possible harmful effects. ω-3 fatty acids are widely used in clinical practice as rather inexpensive, safe, readily available supplemental therapy. Taking advantage of this evidence, several researchers are suggesting that SPMs may have beneficial effects in the complementary treatment of patients with severe forms of SARS-CoV-2 related infection, to counteract the "cytokine storm" observed in these individuals. Well-designed and sized trials in patients suffering from COVID-19 with different degrees of severity are needed to investigate the real impact in the clinical practice of this promising therapeutic approach.

SARS-CoV-2 vaccines: What we know, what we can do to improve them and what we could learn from other well-known viruses.

In recent weeks, the rate of SARS-CoV-2 infections has been progressively increasing all over the globe, even in countries where vaccination programs have been strongly implemented. In these regions in 2021, a reduction in the number of hospitalizations and deaths compared to 2020 was observed. This decrease is certainly associated with the introduction of vaccination measures. The process of the development of effective vaccines represents an important challenge. Overall, the breakthrough infections occurring in vaccinated subjects are in most cases less severe than those observed in unvaccinated individuals. This review examines the factors affecting the immunogenicity of vaccines against SARS-CoV-2 and the possible role of nutrients in modulating the response of distinct immune cells to the vaccination.

Research Progress on the Ability of Astragaloside IV to Protect the Brain Against Ischemia-Reperfusion Injury.

Stroke, a disease with a sudden onset and high morbidity and mortality rates, is difficult to treat in the clinic. Traditional Chinese medicine has become increasingly widely used in clinical practice. Modern pharmacological studies have found that Radix Astragali has a variety of medicinal properties, i.e., immunoregulatory, antioxidative, anti-cancer, anti-diabetes, myocardial protective, hepatoprotective, and antiviral functions. This article reviews the protective effect and mechanism of astragaloside IV, which is extracted from Radix Astragali, on stroke, discusses the cerebroprotective effect of astragaloside IV against ischemia-reperfusion-related complications, offers insight into research prospects, and expands the idea of integrating traditional Chinese and Western medicine treatment strategies and drugs to provide a theoretical reference for the clinical treatment of cerebral ischemia-reperfusion injury and the improvement of stroke prognosis.

SARS-CoV-2: lessons from both the history of medicine and from the biological behavior of other well-known viruses.

SARS-CoV-2 is the etiological agent of the current pandemic worldwide and its associated disease COVID-19. In this review, we have analyzed SARS-CoV-2 characteristics and those ones of other well-known RNA viruses viz. HIV, HCV and Influenza viruses, collecting their historical data, clinical manifestations and pathogenetic mechanisms. The aim of the work is obtaining useful insights and lessons for a better understanding of SARS-CoV-2. These pathogens present a distinct mode of transmission, as SARS-CoV-2 and Influenza viruses are airborne, whereas HIV and HCV are bloodborne. However, these viruses exhibit some potential similar clinical manifestations and pathogenetic mechanisms and their understanding may contribute to establishing preventive measures and new therapies against SARS-CoV-2.

COVID-19, what could sepsis, severe acute pancreatitis, gender differences, and aging teach us?

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a potentially life-threatening disease, defined as Coronavirus Disease 19 (COVID-19). The most common signs and symptoms of this pathological condition include cough, fever, shortness of breath, and sudden onset of anosmia, ageusia, or dysgeusia. The course of COVID-19 is mild or moderate in more than 80% of cases, but it is severe or critical in about 14% and 5% of infected subjects respectively, with a significant risk of mortality. SARS-CoV-2 related infection is characterized by some pathogenetic events, resembling those detectable in other pathological conditions, such as sepsis and severe acute pancreatitis. All these syndromes are characterized by some similar features, including the coexistence of an exuberant inflammatory- as well as an anti-inflammatory-response with immune depression. Based on current knowledge concerning the onset and the development of acute pancreatitis and sepsis, we have considered these syndromes as a very interesting paradigm for improving our understanding of pathogenetic events detectable in patients with COVID-19. The aim of our review is: 1)to examine the pathogenetic mechanisms acting during the emergence of inflammatory and anti-inflammatory processes in human pathology; 2)to examine inflammatory and anti-inflammatory events in sepsis, acute pancreatitis, and SARS-CoV-2 infection and clinical manifestations detectable in patients suffering from these syndromes also according to the age and gender of these individuals; as well as to analyze the possible common and different features among these pathological conditions; 3)to obtain insights into our knowledge concerning COVID-19 pathogenesis. This approach may improve the management of patients suffering from this disease and it may suggest more effective diagnostic approaches and schedules of therapy, depending on the different phases and/or on the severity of SARS-CoV-2 infection.

Critically Ill vs. Non-Critically Ill Patients With COVID-19 Pneumonia: Clinical Features, Laboratory Findings, and Prediction.

Objectives: The objective of this study was to investigate the clinical features and laboratory findings of patients with and without critical COVID-19 pneumonia and identify predictors for the critical form of the disease. Methods: Demographic, clinical, and laboratory data of 63 COVID-19 pneumonia patients were retrospectively reviewed. Laboratory parameters were also collected within 3-5 days, 7-9 days, and 11-14 days of hospitalization. Outcomes were followed up until March 12, 2020. Results: Twenty-two patients developed critically ill pneumonia; one of them died. Upon admission, older patients with critical illness were more likely to report cough and dyspnoea with higher respiration rates and had a greater possibility of abnormal laboratory parameters than patients without critical illness. When compared with the non-critically ill patients, patients with serious illness had a lower discharge rate and longer hospital stays, with a trend towards higher mortality. The interleukin-6 level in patients upon hospital admission was important in predicting disease severity and was associated with the length of hospitalization. Conclusions: Many differences in clinical features and laboratory findings were observed between patients exhibiting non-critically ill and critically ill COVID-19 pneumonia. Non-critically ill COVID-19 pneumonia also needs aggressive treatments. Interleukin-6 was a superior predictor of disease severity.