Long COVID-19 gastrointestinal related disorders and traditional Chinese medicine: A network target-based approach.

The significant number of individuals impacted by the pandemic makes prolonged symptoms after COVID-19 a matter of considerable concern. These are numerous and affect multiple organ systems. According to the World Health Organization (WHO), prolonged gastrointestinal issues are a crucial part of post-COVID-19 syndrome. The resulting disruption of homeostasis underscores the need for a therapeutic approach based on compounds that can simultaneously affect more than one target/node. The present review aimed to check for nutraceuticals possessing multiple molecular mechanisms helpful in relieving Long COVID-19-specific gastrointestinal symptoms. Specific plants used in Keywords Chinese Medicine (TCM) expected to be included in the WHO Global Medical Compendium were selected based on the following criteria: (1) they are widely used in the Western world as natural remedies and complementary medicine adjuvants; (2) their import and trade are regulated by specific laws that ensure quality and safety (3) have the potential to be beneficial in alleviating intestinal issues associated with Long COVID-19. Searches were performed in PubMed, Elsevier, Google Scholar, Scopus, Science Direct, and ResearchGate up to 2023. Cinnamomum cassia, Glycyrrhiza uralensis, Magnolia officinalis, Poria cocos, Salvia miltiorrhiza, Scutellaria baicalensis, and Zingiber officinalis were identified as the most promising for their potential impact on inflammation and oxidative stress. Based on the molecular mechanisms of the phytocomplexes and isolated compounds of the considered plants, their clinical use may lead to benefits in gastrointestinal diseases associated with Long COVID-19, thanks to a multiorgan and multitarget approach.

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.

Effects of environmental parameters and their interactions on the spreading of SARS-CoV-2 in North Italy under different social restrictions. A new approach based on multivariate analysis.

In 2020 North Italy suffered the SARS-CoV-2-related pandemic with a high number of deaths and hospitalization. The effect of atmospheric parameters on the amount of hospital admissions (temperature, solar radiation, particulate matter, relative humidity and wind speed) is studied through about 8 months (May-December). Two periods are considered depending on different conditions: a) low incidence of COVID-19 and very few regulations concerning personal mobility and protection ("free/summer period"); b) increasing incidence of disease, social restrictions and use of personal protections ("confined/autumn period"). The "hospitalized people in medical area wards/100000 residents" was used as a reliable measure of COVID-19 spreading and load on the sanitary system. We developed a chemometric approach (multiple linear regression analysis) using the daily incidence of hospitalizations as a function of the single independent variables and of their products (interactions). Eight administrative domains were considered (altogether 26 million inhabitants) to account for relatively homogeneous territorial and social conditions. The obtained models very significantly match the daily variation of hospitalizations, during the two periods. Under the confined/autumn period, the effect of non-pharmacologic measures (social distances, personal protection, etc.) possibly attenuates the virus diffusion despite environmental factors. On the contrary, in the free/summer conditions the effects of atmospheric parameters are very significant through all the areas. Particulate matter matches the growth of hospitalizations in areas with low chronic particulate pollution. Fewer hospitalizations strongly correspond to higher temperature and solar radiation. Relative humidity plays the same role, but with a lesser extent. The interaction between solar radiation and high temperature is also highly significant and represents surprising evidence. The solar radiation alone and combined with high temperature exert an anti-SARS-CoV-2 effect, via both the direct inactivation of virions and the stimulation of vitamin D synthesis, improving immune system function.

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.

The rationale for a multi-step therapeutic approach based on antivirals, drugs and nutrients with immunomodulatory activity in patients with coronavirus-SARS2-induced disease of different severities.

In December 2019, a novel human-infecting coronavirus, named Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2), was recognised to cause a pneumonia epidemic outbreak with different degrees of severity in Wuhan, Hubei Province in China. Since then, this epidemic has spread worldwide; in Europe, Italy has been involved. Effective preventive and therapeutic strategies are absolutely required to block this serious public health concern. Unfortunately, few studies about SARS-CoV-2 concerning its immunopathogenesis and treatment are available. On the basis of the assumption that the SARS-CoV-2 is genetically related to SARS-CoV (about 82 % of genome homology) and that its characteristics, like the modality of transmission or the type of the immune response it may stimulate, are still poorly known, a literature search was performed to identify the reports assessing these elements in patients with SARS-CoV-induced infection. Therefore, we have analysed: (1) the structure of SARS-CoV-2 and SARS-CoV; (2) the clinical signs and symptoms and pathogenic mechanisms observed during the development of acute respiratory syndrome and the cytokine release syndrome; (3) the modification of the cell microRNome and of the immune response in patients with SARS infection; and (4) the possible role of some fat-soluble compounds (such as vitamins A, D and E) in modulating directly or indirectly the replication ability of SARS-CoV-2 and host immune response.

Cytokine storm in aged people with CoV-2: possible role of vitamins as therapy or preventive strategy.

BACKGROUND: In December 2019, a novel human-infecting coronavirus, SARS-CoV-2, had emerged. The WHO has classified the epidemic as a "public health emergency of international concern". A dramatic situation has unfolded with thousands of deaths, occurring mainly in the aged and very ill people. Epidemiological studies suggest that immune system function is impaired in elderly individuals and these subjects often present a deficiency in fat-soluble and hydrosoluble vitamins. METHODS: We searched for reviews describing the characteristics of autoimmune diseases and the available therapeutic protocols for their treatment. We set them as a paradigm with the purpose to uncover common pathogenetic mechanisms between these pathological conditions and SARS-CoV-2 infection. Furthermore, we searched for studies describing the possible efficacy of vitamins A, D, E, and C in improving the immune system function. RESULTS: SARS-CoV-2 infection induces strong immune system dysfunction characterized by the development of an intense proinflammatory response in the host, and the development of a life-threatening condition defined as cytokine release syndrome (CRS). This leads to acute respiratory syndrome (ARDS), mainly in aged people. High mortality and lethality rates have been observed in elderly subjects with CoV-2-related infection. CONCLUSIONS: Vitamins may shift the proinflammatory Th17-mediated immune response arising in autoimmune diseases towards a T-cell regulatory phenotype. This review discusses the possible activity of vitamins A, D, E, and C in restoring normal antiviral immune system function and the potential therapeutic role of these micronutrients as part of a therapeutic strategy against SARS-CoV-2 infection.

Development and validation of a risk prediction score for severe acute pancreatitis.

INTRODUCTION: The available prognostic scoring systems for severe acute pancreatitis (SAP) have limitations that restrict their clinical value. The aim of this study was to develop a simple model (score) that could rapidly identify those at risk for SAP. METHODS: We derived a risk model using a retrospective cohort of 700 patients by logistic regression and bootstrapping methods. The discriminative power of the risk model was assessed by calculating the area under the receiver operating characteristic curves (AUC). The classification and regression tree (CART) analysis was used to create risk categories. The model was internally validated by a tenfold cross-validation and externally validated in a separate prospective cohort of 194 patients. RESULTS: The incidence of SAP was 9.7% in the derivation cohort and 9.3% in the validation cohort. A prognostic score (We denoted it as the SABP score), ranging from 0 to 10, consisting of systemic inflammatory response syndrome, serum albumin, blood urea nitrogen and pleural effusion, was developed by logistic regression and bootstrapping analysis. Patients could be divided into three risk categories according to total SABP score based on CART analysis. The mean probability of developing SAP was 1.9%, 12.8% and 41.6% in patients with low (0-3), moderate (4-6) and high (7-10) SABP score, respectively. The AUCs of prognostic score in tenfold cross-validation was 0.873 and 0.872 in the external validation. CONCLUSION: Our risk prediction score may assist physicians in predicting the development of SAP.

Prevalence of Colonic Diverticulosis in Patients Affected by Ulcerative Colitis: A Prospective Study.

BACKGROUND: Diverticulosis of the colon is an acquired condition that results from herniation of the mucosa and submucosa through defects in the muscular layer. The true prevalence of colonic diverticulosis is difficult to measure because most individuals are asymptomatic. In particularly, in literature, there are few studies about the prevalence of colonic diverticulosis in patients affected by ulcerative colitis (UC). GOALS: To investigate the prevalence of colonic diverticulosis in UC and in adult patients referred in a single center. STUDY: Consecutive patients, referred to our institution to undergo a colonoscopy for colorectal cancer screening and/or for UC assessment, between January 1, 2014 and December 31, 2014, were studied. RESULTS: Six hundred five consecutive patients were studied: 438 (72.4%) due to colorectal cancer screening (group A) and 167 (27.6%) for UC assessment (group B). Prevalence of colonic diverticulosis was higher in group A than group B (27.8% vs. 10.8%, P<0.0001). Female gender in patients with colonic diverticulosis was higher in group A than group B (55.7% vs. 22.2%, P=0.0106). Sigma and left colon was mainly involved in group A than group B (97.6% vs. 66.7%, P=0.0001), whereas in group B the right colon was mainly involved in group B versus group A (22.2% vs. 0.8%, P=0.0009). CONCLUSIONS: Prevalence of colonic diverticulosis was significantly lower in patients with UC than in control group. UC may, therefore, be a protective factor for colonic diverticulosis occurrence.

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.

The causality between use of glucocorticoids and risk of pancreatitis: a Mendelian randomization study.

Background and aim: To date, the association between glucocorticoid use and the risk of pancreatitis remains controversial. The aim of this study was the investigation of this possible relationship. Methods: We carried out a two-sample Mendelian randomization (MR) analysis using GWAS data from European ancestry, East Asian descendants and the FinnGen Biobank Consortium to evaluate this potential causal relationship. Genetic variants associated with glucocorticoid use were selected based on genome-wide significance (p < 5×10-8). Results: Our MR analysis of European ancestry data revealed no significant causal relationship between glucocorticoid use and AP (IVW: OR=1.084, 95% CI= 0.945-1.242, P=0.249; MR-Egger: OR=1.049, 95% CI= 0.686-1.603, P=0.828; weighted median: OR=1.026, 95% CI= 0.863-1.219, P=0.775) or CP (IVW: OR=1.027, 95% CI= 0.850-1.240, P=0.785; MR-Egger: OR= 1.625, 95% CI= 0.913-2.890, P= 0.111; weighted median: OR= 1.176, 95% CI= 0.909-1.523, P= 0.218). Sensitivity analyses, including MR-Egger and MR-PRESSO, indicated no evidence of pleiotropy or heterogeneity, confirming the robustness of our findings. Multivariable MR analysis adjusted for alcohol consumption, BMI, cholelithiasis and C-reactive protein levels supported these findings. Replicated analysis was performed on datasets from the FinnGen Biobank Consortium and East Asian descendants, and similar results were obtained. Conclusions: This MR analysis suggests that there is no causal association between glucocorticoid use and the risk of pancreatitis.

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.

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.

Real-world efficacy and safety of vedolizumab in managing ulcerative colitis versus Crohn's disease: results from an Italian multicenter study.

BACKGROUND: Vedolizumab (VDZ) can be used to treat refractory ulcerative colitis (UC) and Crohn's disease (CD). We assessed whether there are differences in treating UC vs CD with VDZ. RESEARCH DESIGN AND METHODS: Mayo score in UC and the Harvey-Bradshaw Index (HBI) in CD scored the clinical activity. Achievement and maintenance of clinical remission during the follow-up, and safety were the primary endpoints. RESULTS: 729 patients (475 with UC and 254 with CD), median follow-up of 18 (IQR 6-36) months, were enrolled. Clinical remission at the 6th month of treatment was achieved in 488 (66.9%) patients (74.4% in CD vs 62.9% in UC, p<0.002) while, during the follow-up, no difference was found (81.5% in the UC group and 81.5% pts in the CD group; p=0.537). The clinical remission at the 6th month of treatment (p=0.001) and being naïve to biologics (p<0.0001) were significantly associated with prolonged clinical remission. The clinical response was significantly higher in UC (90.1%) vs CD (84.3%) (p=0.023), and surgery occurred more frequently in CD (1.9% in UC vs 5.1% in CD, p=0.016). CONCLUSION: We found differences when using VDZ in UC vs CD in real life. These parameters can help the physician predict this drug's longterm efficacy.

Use of tofacitinib as first or second-line therapy is associated with better outcomes in patients with ulcerative colitis: data from a real-world study.

BACKGROUND: Data regarding the real-world (RW) use of tofacitinib (TOF) in patients with ulcerative colitis (UC) are limited. We aimed to investigate TOF's RW efficacy and safety in Italian UC patients. RESEARCH DESIGN AND METHODS: A retrospective assessment of clinical and endoscopic activity was performed according to the Mayo score. The primary endpoints were to evaluate the effectiveness and safety of TOF. RESULTS: We enrolled 166 patients with a median follow-up of 24 (IQR 8-36) weeks. Clinical remission was achieved in 61/166 (36.7%) and 75/166 (45.2%) patients at 8-week and 24-week follow-ups, respectively. The optimization was requested in 27 (16.3%) patients. Clinical remission was achieved more frequently when TOF was used as a first/second line rather than a third/fourth line treatment (p = 0.007). Mucosal healing was reported in 46% of patients at the median follow-up time. Colectomy occurred in 8 (4.8%) patients. Adverse events occurred in 12 (5.4%) patients and severe in 3 (1.8%). One case of simple Herpes Zoster and one of renal vein thrombosis were recorded. CONCLUSIONS: Our RW data confirm that TOF is effective and safe in UC patients. It performs remarkably better when used as the first/second line of treatment.

Simultaneous laparoscopic removal of a Todani type II choledochal cyst and a microlithiasic cholecystitis.

Diverticula of the choledochus, better known as Todani type II cysts, are very rare and represent a predominantly pediatric pathology. Their identification by radiological methods, even if occasional, requires clinical doctors to request a surgical consultation, even for asymptomatic subjects, to proceed with their removal, given the risk of associated neoplasms. The laparoscopic approach for surgical treatment of these cysts has been recently introduced with excellent results. Due to the poor clinical records, currently there are neither shared protocols about their management nor long-term follow-up of operated patients. We report a case of an adult female suffering for years from biliary colic due to the presence of a duodenal diverticulum associated with microlithiasis' cholecystitis, who was laparoscopically treated, with excellent results in terms of symptomatic regression, reduced hospitalization, and no surgery-related complications.

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.

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.

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.

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.

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.