Allergic hyper-carcinoembryonic antigen syndrome: A syndrome summarized by case series.

Allergic respiratory diseases can increase serum carcinoembryonic antigen levels. We report three cases experiencing allergic symptoms that proved refractory to inhaled corticosteroids but exhibited a positive response to long-term treatment with oral corticosteroids. This response was characterized by a synchronous alteration in serum eosinophil counts and carcinoembryonic antigen levels. Immunofluorescence assays indicated localized carcinoembryonic antigen production within eosinophils. In addition, we conducted a systematic review of patients exhibiting similar characteristics on PubMed. After comprehensively reviewing this unique pathophysiological condition, we herein introduced a novel term "Allergic hyper-carcinoembryonic antigen syndrome," defined by the following criteria: (1) recurrent asthmatic attacks; (2) eosinophilia or pulmonary eosinophilic infiltrations accompanied by elevated serum carcinoembryonic antigen levels; (3) pulmonary lesions determined by imaging or biopsy; (4) exclusion of malignancy and infections; and (5) responsive to systemic corticosteroids. Allergic hyper-carcinoembryonic antigen syndrome suggests systemic corticosteroids should be introduced early when managing allergic patients with both eosinophilia and elevated serum carcinoembryonic antigen levels.

Development and Validation of a Nomogram for Predicting Tigecycline-Related Coagulopathy: A Retrospective Cohort Study.

Background: Although tigecycline is an effective drug against drug-resistant bacteria, it demonstrated a higher all-cause mortality than comparator antibiotics and a high incidence of coagulation disorders which can be accompanied by severe bleeding. At present, a predictive model for tigecycline-related coagulopathy is not readily available, and the prognostic value of coagulopathy in tigecycline-administered patients has not been elucidated. In this paper, we investigate the association between tigecycline-related coagulopathy and in-hospital mortality to develop a nomogram for the prediction of tigecycline-related coagulopathy. Methods: This retrospective cohort study includes 311 adults prescribed with tigecycline from 2018 to 2020. The primary cohort and validation cohort were constructed by dividing the participants in a ratio of 7:3. The endpoint is tigecycline-related coagulopathy, defined as a condition with no abnormality in coagulation prior to tigecycline application but developed the following symptoms upon prescription: activated partial thromboplastin time (APTT) extended by >10 s than the upper limit of normal (ULN), prothrombin time (PT) prolonged for >3 s than the ULN or reduced serum level of fibrinogen to <2.0 g/L. A predictive nomogram based on logistic regression was subsequently constructed. Results: Tigecycline intake for over 7 days, combined other antibiotics, initial PT, initial fibrinogen and estimated glomerular filtration rate (eGFR), are independent prognostic factors of tigecycline-related coagulopathy. The primary and validation cohort each has an area under the receiver operating characteristic curve (AUC) of 0.792 (0.732-0.851) and 0.730 (0.629-0.832) for nomogram, respectively. Furthermore, the fitted calibration curve illustrated adequate fit of the model, while the decision curve analysis demonstrated good clinical value. Survival curves showed a high mortality rate among patients with tigecycline-related coagulopathy. Conclusion: This nomogram exhibited helpful clinical value in predicting tigecycline-related coagulopathy that could reduce the high mortality rate of patients prescribed with tigecycline.

Successful combinatorial therapy of sirolimus and neuraminidase inhibitors in a patient with highly pathogenic avian influenza A (H5N6) virus: a case report.

Background: Highly pathogenic avian influenza A (H5N6) virus poses a continuous threat to human health since 2014. Although neuraminidase inhibitors (NAIs) are prescribed in most patients infected with the H5N6 virus, the fatality remains high, indicating the need for an improved treatment regimen. Sirolimus, an inhibitor of the mammalian target of rapamycin (mTOR), has been reported to reduce viral replication and improve clinical outcomes in severe H1N1 infections when combined with oseltamivir. Here, we report the first case of severe H5N6 pneumonia successfully treated by sirolimus and NAIs. Case Description: A 22-year-old man developed high fever and chills on September 24, 2018 (Day-0) and was hospitalized on Day-3. Influenza A (H5N6) was identified on Day-6 from a throat swab specimen. Despite the administration of NAIs and other supportive measures, the patient's clinical conditions and lung images showed continued deterioration, accompanied by persistently high viral titers. Consequently, sirolimus administration (rapamycin; 2 mg per day for 14 days) was started on Day-12. His PaO2/FiO2 values and Sequential Organ Failure Assessment (SOFA) score gradually improved, and imaging outcomes revealed the resolution of bilateral lung infiltrations. The viral titer gradually decreased and turned negative on Day-25. Sirolimus and NAIs were stopped on the same day. The patient was discharged on Day-65. Based on observations from a 2-year follow-up, the patient was found to be in a good condition without complications. Conclusions: In conclusion, sirolimus might be a novel and practical therapeutic approach to severe H5N6-associated pneumonia in humans.

rs1840680 single nucleotide polymorphism in Pentraxin 3: a potential protective biomarker of severe community-acquired pneumonia.

OBJECTIVE: Single nucleotide polymorphisms (SNPs) of pentraxin 3 (PTX3) are associated with various outcomes of lung infections. This study aimed to analyze the relationship between PTX3 polymorphisms and the severity of community-acquired pneumonia (CAP). METHODS: This is a retrospective case-control study comprising 43 patients with severe CAP (SCAP) and 97 patients with non-severe CAP. Three SNPs in the PTX3 gene (rs2305619, rs3816527, and rs1840680) from peripheral blood samples were genotyped by real-time polymerase chain reaction. The association between each SNP and the CAP severity was analyzed by logistic regression analysis. RESULTS: We found that the rs1840680 polymorphism was significantly associated with CAP clinical severity. However, no such association was observed for the genotypes and allele frequencies of rs2305619 or rs3816527. The PTX3 rs1840680 AG genotype was an independent factor for a lower risk of SCAP after multivariate logistic regression analysis. Male sex and coronary heart disease were associated with an increased risk of SCAP. CONCLUSIONS: The PTX3 rs1840680 AG genotype was found to be associated with a lower risk of SCAP, and may serve as a potential protective biomarker to help clinical judgment and management.

Pentraxin-3 polymorphisms and pulmonary fungal disease in non-neutropenic patients.

BACKGROUND: Pentraxin 3 (PTX3) plays a non-redundant role in innate immunity against fungal diseases. Although single nucleotide polymorphisms (SNPs) of PTX3 are associated with a higher risk of invasive aspergillosis among the immunosuppressed population and chronic obstructive pulmonary disease patients, it is unknown whether PTX3 genetic variants influence the risk of pulmonary fungal disease in immunocompetent patients. METHODS: To investigate the association between PTX3 gene polymorphisms and pulmonary mycosis in non-neutropenic patients, we conducted a case-control study in a tertiary hospital department. Forty-five patients were identified using the criteria of the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC-MSG) and enrolled in the case group. Of these patients, 15 had allergic bronchopulmonary aspergillosis (ABPA), 10 had invasive pulmonary aspergillosis (IPA), 18 had pulmonary cryptococcosis, and 2 had other types of pulmonary mycosis. One hundred and twenty-two non-neutropenic inpatients not infected by fungal disease were randomly selected as the control group. We detected three SNPs (rs2305619, rs3816527, and rs1840680) within the PTX3 gene using polymerase chain reaction sequencing and compared their associations with different types of pulmonary fungal disease. RESULTS: Three SNPs were consistent with Hardy-Weinberg equilibrium (HWE). SNP rs2305619 was in linkage disequilibrium with rs3816527 (D'=0.85) and rs1840680 (D'=0.85), respectively. There was no difference in the genotypic distribution and haplotype frequency of the SNPs between the case group and the control group. When we focused on invasive mold infections as a subgroup, we found that the SNP rs3816527 CC homozygote was associated with a higher risk of IPA (OR, 7.37; 95% CI, 0.93-44.44; P=0.033), while the rs3816527 AA homozygote might lower the risk of pulmonary cryptococcosis (OR, 0.35; 95% CI, 0.11-0.96; P=0.047). No genotypic distribution differences were observed for the other two SNPs (rs2305619 and rs1840680). When it came to the comparison between ABPA subgroup and control group, no difference in single nucleotide polymorphism was observed. CONCLUSIONS: This study showed that the SNP rs3816527 is associated with IPA in non-neutropenic patients. Further investigations in large populations are needed to validate this genetic predisposition. Functional studies are also required.

Spontaneous pneumomediastinum and subcutaneous emphysema in avian influenza A (H5N6) human pneumonia.

The pneumomediastinum and subcutaneous emphysema can repetitively occur in human H5N6 virus pneumonia. Prompt treatment of this uncommon complication is important for successful rescue of patients with H5N6 virus pneumonia.

Intra-operative blood transfusion significantly increases the risk of post-operative pulmonary embolism.

BACKGROUND: Pulmonary embolism (PE) is a serious and preventable complication after surgery. Blood transfusion is a common event during surgery. The aim of the present study was to identify whether intra-operative blood product transfusions increase the risk of symptomatic post-operative PE. METHODS: A retrospective, single-center case-control study at Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University between 1 January 2013 and 31 December 2016 was performed. Adult hospitalized patients with confirmed symptomatic PE after surgery were defined as case group. Each patient was matched with two adult patients without symptomatic PE who underwent the same procedure on the same day or within one week. Perioperative data especially detailed blood transfusion was collected. Forward stepwise logistic regression analysis was performed. RESULTS: During the study period, altogether 188,512 procedures were included, and postoperative PE were confirmed in 40 (0.02%) patients. Twelve (30.0%) case patients and 16 (20.0%) control patients received intra-operative blood transfusion. Intra-operative blood transfusion was revealed as a significant predictor for symptomatic post-operative PE (OR 80.669, 95% CI: 3.312-1,964.641, P=0.007), along with female sex (OR 86.921, 95% CI: 4.242-1,781.124, P=0.004), older age (OR 1.078, 95% CI: 1.005-1.156, P=0.035), longer length of stay before surgery (OR 1.124, 95% CI: 1.040-1.214, P=0.003) and longer operation time (OR 1.013, 95% CI: 1.002-1.025, P=0.024). CONCLUSIONS: Intra-operative blood transfusion was associated with an increased risk of symptomatic post-operative PE. PE prophylaxis and selective screening should be considered in patients who had received intra-operative blood transfusion, especially in female patients.

The impact of previous hospitalization in the preceding 90 days on the outcome in critically ill patients with gram-negative bloodstream infection.

We conducted a retrospective cohort study to evaluate the impact of previous hospitalization in the preceding 90 days on mortality in critically ill patients with gram-negative bloodstream infection (BSI) and to identify the risk factors for 30-day mortality in these patients. Of 89 critically ill patients with gram-negative BSI, 42 patients had previous hospitalization in the preceding 90 days. Multivariate Cox regression analysis revealed previous hospitalization in the preceding 90 days as a significant predictor for 30-day mortality (hazard ratio [HR], 2.10; 95% confidence interval [CI], 1.11-3.94; P = 0.022), along with Acute Physiology and Chronic Health Evaluation II score at BSI onset (HR, 1.08; 95% CI, 1.04-1.12; P < 0.001), liver cirrhosis (HR, 3.61; 95% CI, 1.46-8.94; P = 0.006), and inappropriate definitive antimicrobial therapy (HR, 4.28; 95% CI, 2.17-8.45; P < 0.001). The effect of previous hospitalization in the preceding 90 days should be considered in evaluating the risk for 30-day mortality when treating such patients, and further study is required.

Update in diagnosis and therapy of coexistent chronic obstructive pulmonary disease and chronic heart failure.

Chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) frequently coexist in clinical practice as they share the same risk factors. The manifestations of COPD and CHF are similar. Exertional dyspnoea, easy fatigability and reduced exercise tolerance are common to COPD and CHF and required careful interpretation. Pulmonary function tests, plasma natriuretic peptides, echocardiography and cardiovascular magnetic resonance imaging should be carried out to acquire the objective evidence of pulmonary and cardiac function when necessary. Robust studies indicate that patients with COPD tolerate the cardioselective ß-blockers well, so it should not be denied to CHF patients with concomitant COPD. Low-dose initiation and gradual uptitration of cardioselective ß-blockers is currently recommended. However, ß(2)-agonists should be used with cautions in COPD patients with CHF, especially in acute exacerbations. Statins, angiotensin-converting enzyme inhibitors, and angiotensin-receptor blockers may reduce the morbidity and mortality of the patients with COPD.