A case of chlamydia psittaci caused severe pneumonia and meningitis diagnosed by metagenome next-generation sequencing and clinical analysis: a case report and literature review.

BACKGROUND: Psittacosis, which is also known as parrot fever, is Chlamydia psittaci (C. psittaci) caused infectious disease. The clinical manifestations vary from asymptomatic infection to severe atypical pneumonia or even fatal meningitis. Early recognition of psittacosis is difficult because of its nonspecific clinical manifestations. Culture and gene probe techniques for C. psittaci are not available for routine clinical use, which makes the diagnosis difficult too. Although psittacosis has increasingly been recognized and reported in recent years, cure of severe pneumonia complicated with meningitis, with etiologic diagnosis aided by the use of metagenomic next-generation sequencing (mNGS), is still uncommon. So, it is necessary to report and review such potentially fatal case. CASE PRESENTATION: This report describes a 54-year-old woman with C. psittaci caused severe atypical pneumonia and meningitis. She presented with symptoms of fever, dry cough and dyspnea, accompanied by prominent headache. Her condition deteriorated rapidly to respiratory failure and lethargy under the treatment of empirical antibacterial agents, and was treated with invasive mechanical ventilation soon. She denied contact with birds, poultry or horses, but unbiased mNGS of both the bronchoalveolar lavage fluid (BALF) and the cerebrospinal fluid (CSF) identified sequence reads corresponding to C. psittaci infection, and there was no sequence read corresponding to other probable pathogens. Combined use of targeted antimicrobial agents of tetracyclines, macrolides and fluoroquinolones was carried out, and the patient's condition improved and she was discharged home 28 days later. Her status returned close to premorbid condition on day 60 of follow-up. CONCLUSIONS: When clinicians come across a patient with atypical pneumonia accompanied by symptoms of meningitis, psittacosis should be taken into consideration. mNGS is a promising detection method in such condition and is recommended.

Aggravated MRSA pneumonia secondary to influenza A virus infection is derived from decreased expression of IL-1ß.

Secondary methicillin-resistant Staphylococcus aureus (MRSA) infection is a cause of severe pneumonia with high mortality during influenza A virus (IAV) pandemics. Alveolar macrophages (AMs) mount cellular defenses against IAV and MRSA infection, which occurs via the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome. However, the activity and function of the NLRP3 inflammasome in MRSA pneumonia secondary to IAV infection remain unclear. To clarify this, we studied MRSA infection secondary to IAV both in vitro and in mouse model. The expression of the NLRP3 inflammasome was evaluated by quantitative reverse transcription polymerase chain reaction, immunofluorescence, Western blot, and enzyme-linked immunosorbent assay. The lung pathology and the rate of weight change were observed. We found that IAV infection for 1 week activated NLRP3 inflammasome. The enhanced expression of NLRP3, caspase-1, and cleaved caspase-1 was associated with MRSA infection secondary to IAV, but the expression of interleukin (IL)-1ß decreased in superinfection with MRSA both in vitro and in vivo. The aggravated inflammatory pathology in MRSA pneumonia secondary to IAV infection was associated with decreased expression of IL-1ß. And increased weight loss in MRSA pneumonia secondary to IAV infection was related to decreased concentration of IL-1ß in serum. It infers that superinfection with MRSA reduces expression of IL-1ß someway, and decreased expression of IL-1ß impairs the host immunity and leads to aggravated pneumonia. These results contributed to our understanding of the detailed activity of the NLRP3 inflammasome, IL-1ß, and their relationship with aggravation of MRSA pneumonia secondary to IAV infection. Immunotherapy targeting the IL-1ß signaling pathway could be possible therapeutic strategy for secondary MRSA pneumonia.

Successful treatment of mycobacterial infection associated hemophagocytic lymphohistiocytosis with etoposide and anti-tuberculous therapy: a case report.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare and potentially life-threatening disorder characterized by an exacerbated but ineffective inflammatory response, which can be classified as primary and secondary HLH. HLH associated with Mycobacterium tuberculosis is uncommon. This case report accounted an immunocompetent patient who was confirmed to be Mycobacterium infection, or rather, highly suspected tuberculosis (TB) associated HLH, with a favorable outcome. CASE PRESENTATION: A 36-year-old man presented with persistent fever, pancytopenia, and hyperferritinemia. A bone marrow smear demonstrated hemophagocytosis, and pathological examination of lung biopsy was positive for acid-fast bacilli, which established the diagnosis of Mycobacterium infection and HLH. Then the patient treated successfully with anti-TB therapy, along with 8 weeks of etoposide. CONCLUSION: This case emphasizes that HLH should be kept in mind when clinicians encounter a patient with severe infection presenting with pancytopenia and hyperferritinemia. Given the high mortality, early diagnosis and appropriate therapy can provide patients with a favorable prognosis.

A Case of Hemophagocytic Lymphohistiocytosis Secondary to Ralstonia Solanacearum Infection.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH), as known as Hemophagocytic syndrome (HPS), is deemed to a severe clinical syndrome caused by excessive human being immune system activation. Bacteria of Ralstonia genus is a non-fermentative, gram-negative bacillus and also in the category of human opportunistic pathogenic bacteria. In this article, authors report a rare case of Hemophagocytic lymophohistiocytosis which probably was triggered by Ralstonia solanacearum (R. solanacearum) infection. METHODS: Hematologic investigation, biochemical examination, high throughput genetic test for infectious agents and bone marrow puncture. RESULTS: The patient achieved complete remission and no signs of relapse have as yet been found. CONCLUSIONS: The bacteria of Ralstonia genus merely infect humans, and there were no reports about the infection of R. solanacearum in humans and secondary HLH. The prognosis of the patient in this case was very good. This result, we think shows that the relationship between HLH and R. solanacearum infection should be taken into the diagnosis process. Recognition of this will promote the correct diagnosis in clinical work.

Regulatory effects of miR-155 and miR-146a on repolarization and inflammatory cytokine secretion in human alveolar macrophages in vitro.

Macrophages play an important role in inflammatory responses; however, miRNA-mediated repolarization of macrophages is essential for fulfilling this function. To clarify a series of changes at the RNA level in alveolar macrophages under normal and inflammatory conditions, bronchial alveolar lavage liquid (BALF) was collected from healthy volunteers or patients with pneumonia. This approach, which differs from that used in previously, provides more accurate information about the states of macrophages in different lung microenvironments. In this study, the density plots of macrophage subtypes (M1 and M2) in the BALF of healthy volunteers differed from that of the patients with pneumonia. The M2 subtype dominated in healthy volunteers and was rapidly repolarized to M1 in response to miRNA-mediated gene regulation. Differential miRNA expression in the two macrophage subtypes revealed lower expression of miR-155 and MIR-146a in patients with pneumonia compared with healthy volunteers; this may be related to inflammation and the use of anti-inflammatory drugs. We also found increased TNF-α and IL-6 expression at the RNA level, while macrophage galactose-type C-type lectin 1 (MGL-1) expression decreased with downregulation of miR-155 and miR-146a expression. These results indicate that the gene regulation mediated by miR-155 and miR-146a contributes to human alveolar macrophage phenotype repolarization, thus leading to an early switch from pro-inflammatory to anti-inflammatory cytokine production.

Protective effects of caffeoylxanthiazonoside isolated from fruits of Xanthium strumarium on sepsis mice.

CONTEXT: The fruit of Xanthium strumarium L. (Asteraceae) has been used for the treatment of various inflammatory diseases. OBJECTIVE: This study investigates the protective effect of caffeoylxanthiazonoside (CYXD) isolated from fruits of X. strumarium on sepsis mice in vitro and in vivo. MATERIALS AND METHODS: Cecal ligation and puncture (CLP) operation was used to establish the sepsis mice model, and sham mice were also performed. CYXD was administered by intraperitoneal injection (10, 20, and 40 mg/kg/d), then the survival rate was measured in 96 h. Additionally, sepsis mice were induced by injection LPS (2 mg/kg); CYXD was administered by intraperitoneal injection (10, 20, and 40 mg/kg/d), then mice were sacrificed, and serum levels of TNF-α and IL-6 were determined by ELISA assay. Furthermore, the ability of CYXD to neutralize LPS was measured by using the LAL test, and expressions of TNF-α, IL-6 were determined by using real-time fluorogenic PCR. RESULTS: Results indicated that CYXD significantly elevated survival rates of sepsis mice induced by CLP (p < 0.05) with survival rates of 35%, 45%, and 65%. Furthermore, the LPS level was decreased obviously by CYXD (1, 2, and 4 mg/L) (p < 0.05). Additionally, CYXD (10, 20, and 40 mg/kg) can not only significantly decrease TNF-α and IL-6 levels induced by LPS in mice's serum (p < 0.05), but also inhibit mRNA expressions of TNF-α and IL-6 induced by LPS in RAW 264.7 cells at doses of 20, 40, and 80 µg/mL (p < 0.05). CONCLUSION: Our study demonstrated that CYXD has significant protective effects on sepsis mice.

Diagnostic and Prognostic Values of KLF5 and RUNX1 in Acute Kidney Injury in Septic Patients.

Diagnostic and prognostic values of Kruppel-like factor 5 (KLF5) and Runt-related transcription factor 1 (RUNX1) were determined in sepsis-induced acute kidney injury (SI-AKI). The study included 120 septic patients and set two groups: SI-AKI group (n = 60) or non-AKI group (n = 60). Fasting venous blood was drawn, and KLF5 and RUNX1 levels were measured. The receiver operating characteristic curve was plotted for diagnostic evaluation of KLF5 and RUNX1 in SI-AKI. The correlation between KLF5 and RUNX1 and serum creatinine (Scr), cystatin C (Cys-C), and kidney injury molecule 1 (KIM-1) were assessed by Pearson method. Predictive values of KLF5 and RUNX1 in 28-day survival of SI-AKI patients were considered by Kaplan-Meier survival curves and multivariate Cox regression analysis. Serum KLF5 and RUNX1 in SI-AKI patients were upregulated. Serum KLF5 and RUNX1 were of high diagnostic value in distinguishing SI-AKI patients from non-AKI patients. KLF5 and RUNX1 were in a positive correlation with Scr, Cys-C, and KIM-1, respectively. The 28-day survival of SI-AKI patients with high serum KLF5 or RUNX1 expression was poor, and serum KLF5 and RUNX1 expression were independently correlated with SI-AKI patients' survival. KLF5 and RUNX1 have diagnostic and prognostic values in SI-AKI patients.

Tumor-infiltrating lymphocytes predict response to chemotherapy in patients with advance non-small cell lung cancer.

Accumulating preclinical evidence suggests that anticancer immune responses contribute to the success of chemotherapy. The predictive significance of tumor-infiltrating lymphocytes (TILs) for response to neoadjuvant chemotherapy in non-small cell lung cancer (NSCLC) remains unknown. The aim of this study was to investigate the prognostic and predictive value of TIL subtypes in patients with advanced NSCLC treated with platinum-based chemotherapy. In total, 159 patients with stage III and IV NSCLC were retrospectively enrolled. The prevalence of CD3(+), CD4(+), CD8(+) and Foxp3(+) TILs was assessed by immunohistochemistry in tumor tissue obtained before chemotherapy. The density of TILs subgroups was treated as dichotomous variables using the median values as cutoff. Survival curves were estimated by the Kaplan-Meier method, and differences in overall survival between groups were determined using the Log-rank test. Prognostic effects of TIL subsets density were evaluated by Cox regression analysis. The presence of CD3(+), CD4(+), CD8(+), and FOXP3(+) TILs was not correlated with any clinicopathological features. Neither the prevalence of TILs nor combined analysis displayed obvious prognostic performances for overall survival in Cox regression model. Instead, higher FOXP3(+)/CD8(+) ratio in tumor sites was an independent factor for poor response to platinum-based chemotherapy in overall cohort. These findings suggest that immunological CD8(+) and FOXP3(+)Tregs cell infiltrate within tumor environment is predictive of response to platinum-based neoadjuvant chemotherapy in advanced NSCLC patients. The understanding of the clinical relevance of the microenvironmental immunological milieu might provide an important clue for the design of novel strategies in cancer immunotherapy.

Serum human epididymis secretory protein 4 correlates with sepsis-associated acute respiratory distress syndrome and 28-day mortality in critically ill patients.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a severe disease with high mortality, and its primary cause is sepsis. The aim of this study was to detect and evaluate the role of Human epididymis protein 4 (HE4) in sepsis-related ARDS. METHODS: One hundred and twenty-three critically ill sepsis patients with/without ARDS and 102 healthy controls were enrolled in this study. Blood samples were collected upon admission for quantitative testing of HE4 by chemiluminescent microparticle immunoassay (CMIA). ROC curve analysis and Spearman's correlation analysis were conducted to determine the diagnostic and prognostic value of HE4. RESULTS: Compared with controls, the serum HE4 concentrations of sepsis patients were elevated, and levels in sepsis patients with ARDS were significantly higher (all p < 0.0001). Moreover, HE4 concentrations were strongly correlated with the clinical severity characteristics of sepsis patients, and ROC curve suggested that the AUC of HE4 applied to discriminate sepsis-ARDS patients from sepsis patients was 0.903. HE4 was also found to be a prognostic biomarker of clinical severity and 28-day mortality among critically ill sepsis patients. Logistic regression analysis showed that HE4 was an independent factor for diagnosis of ARDS. Meanwhile, ROC curve analysis showed that the cut-off value of serum HE4 to discriminate 28-day mortality from sepsis patients (AUC: 0.782) was 646.5 pmol/L. CONCLUSIONS: The concentration of serum HE4 in patients with sepsis-related ARDS was markedly increased and was significantly correlated with mortality, which suggests that serum HE4 could be a promising diagnostic and prognostic biomarker for ARDS in sepsis patients.

Inhibitory effects of lipoteichoic acid from Staphylococcus aureus on platelet function and platelet-monocyte aggregation.

OBJECTIVE: Lipoteichoic acid (LTA) from Staphylococcus aureus has been demonstrated to inhibit agonist-stimulated platelet aggregation. However, its effects on platelet inflammatory mediator release and platelet-monocyte aggregation are still unclear. In the present study, LTA is examined for its anti-inflammatory properties and effects on platelet-monocyte aggregation. METHODS: Blood samples were obtained from 5 healthy volunteers who had taken no medicine in the previous 2 weeks. Washed platelets were prepared and incubated with LTA (0.5-2.0 µg/mL), then platelet aggregation, P-selectin expression, and soluble CD40L (sCD40L) release were measured by light transmission aggregometry, flow cytometry and enzyme-linked immunoassays, respectively. Platelet-monocyte aggregate formation in whole blood was measured by flow cytometry. Thrombin was used as a stimulant. RESULTS: LTA dose-dependently decreased platelet aggregation from 89.32 ± 10.24% to 36.28 ± 9.01% (P < 0.05), sCD40L release from 3.28 ± 0.76 to 1.13 ± 0.45 ng/mL (P < 0.05) and surface P-selectin expression from 82.01 ± 11.20 to 22.78 ± 6.42% (P < 0.05). In human whole blood, 1.0 µg/mL LTA inhibited platelet-monocyte aggregation from 78.19 ± 10.94 to 38.24 + 8.74% (P < 0.05). CONCLUSIONS: These results indicate that LTA from S. aureus can inhibit platelet-dependent inflammatory mediator release and platelet-monocyte aggregation. These findings suggest that LTA-mediated functional alteration of platelets may contribute to immune evasion of S. aureus.

Factors associated with the outcome of life-threatening necrotizing pneumonia due to community-acquired Staphylococcus aureus in adult and adolescent patients.

BACKGROUND: Although community-acquired Staphylococcus aureus pneumonia with highly virulent Panton-Valentine leukocidin (PVL)-positive strains, a severe disease with significant lethality, is rare, especially in adult and adolescent patients, recent reports highlight that these infections are on the rise. OBJECTIVES: To describe the demographic and clinical features of reported cases of life-threatening community-acquired S. aureus pneumonia with usually PVL-positive strains in adult and adolescent patients, to evaluate the variables related to death, and to select a more appropriate antimicrobial treatment for this potentially deadly disease. METHODS: We summarized all of the 92 reported cases and our case. The effect of 5 variables on mortality was measured using logistic regression. RESULTS: S. aureus community-acquired pneumonia (CAP) with usually PVL-positive strains is a severe disease with significant lethality, i.e. 42.9%; a short duration of the time from the onset of symptoms to death, i.e. 5.5 ± 10.1 days, and prolonged hospital admissions, i.e. 33.2 ± 29.5 days. Seventy-three cases have been tested for the gene for PVL, and 71 strains have been found to carry the PVL gene. Logistic regression analysis showed that leucopenia (p = 0.002), influenza-like symptoms or laboratory-confirmed influenza (p = 0.011), and hemoptysis (p = 0.024) were the factors associated with death. Antibiotic therapies inhibiting toxin production were associated with an improved outcome in these cases (p = 0.007). CONCLUSIONS: Physicians should pay special attention to those patients who acquired severe CAP during influenza season and have flu-like symptoms, hemoptysis, and leucopenia, and they should consider S. aureus more frequently among the possible pathogens of severe CAP. Empiric therapy for severe CAP with this distinct clinical picture should include coverage for S. aureus. Targeted treatment with antimicrobials inhibiting toxin production appears to be a more appropriate selection.

Disseminated Human Parvovirus B19 Infection Induced Multiple Organ Dysfunction Syndrome in an Adult Patient With Alcoholic Hepatitis Complicated by Hemolytic Anemia: A Case Report and Literature Review.

Background: Human parvovirus B19 (B19) can cause acute hepatitis and is attributed to the high mortality of alcoholic hepatitis (AH). B19 infection is generally self-healing in previously healthy people, but it can cause fatal effects in some high-risk groups and increase its virulence and infectivity. Disseminated B19 infection-induced multiple organ dysfunction syndrome (MODS) in patients with AH has not been reported yet. Here, we described B19 viremia in an adult patient with AH accompanied by hemolytic anemia (HA), leading to disseminated infection and secondary MODS, as well as self-limiting B19 infections in seven nurses caring for him. Meanwhile, we reviewed the literature on AH and B19 infection. Case Presentation: A 43-year-old male patient with AH accompanied by HA was transferred to the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China, on March 31, 2021. After supportive treatment, his transaminase and bilirubin levels were reduced, but his anemia worsened. He received a red blood cell (RBC) infusion on April 9 for hemoglobin (Hb) lower than 6 g/dl. On April 13, he suddenly had a high fever. Under empirical anti-infection, his high fever dropped and maintained at a low fever level; however, his anemia worsened. On April 25, he was transferred to the medical intensive care unit (MICU) due to severe pneumonia, acute respiratory distress syndrome (ARDS), acute aplastic crisis (AAC), and hemophagocytic syndrome (HPS), which were subsequently confirmed to be related to B19 infection. After methylprednisolone, intravenous immunoglobulin (IVIG), empirical anti-infection, and supportive treatment, the lung infection improved, but hematopoietic and liver abnormalities aggravated, and systemic B19 infection occurred. Finally, the patient developed a refractory arrhythmia, heart failure, and shock and was referred to a local hospital by his family on May 8, 2021. Unfortunately, he died the next day. Fourteen days after he was transferred to MICU, seven nurses caring for him in his first two days in the MICU developed self-limiting erythema infectiosum (EI). Conclusions: B19 infection is self-limiting in healthy people, with low virulence and infectivity; however, in AH patients with HA, it can lead to fatal consequences and high contagion.

Disseminated Tuberculosis Associated Hemophagocytic Lymphohistiocytosis in a Pregnant Woman With Evans syndrome: A Case Report and Literature Review.

Background: Tuberculosis (TB) is a leading cause of morbidity and mortality in underdeveloped and developing countries. Disseminated TB may induce uncommon and potentially fatal secondary hemophagocytic lymphohistiocytosis (HLH). Timely treatment with anti-tuberculosis therapy (ATT) and downmodulation of the immune response is critical. However, corticosteroid treatment for TB-associated HLH remains controversial. Herein, we report a successful case of disseminated TB-associated HLH in a pregnant woman with Evans syndrome accompanied by a literature review. Case Presentation: A 26-year-old pregnant woman with Evans syndrome was transferred to the Third Affiliated Hospital of Sun Yat-Sen University because of severe pneumonia. She presented with cough, fever, and aggravated dyspnea. Nested polymerase chain reaction for Mycobacterium tuberculosis (M. tuberculosis) complex in sputum was positive. Sputum smear sample for acid-fast bacilli was also positive. Metagenome next-generation sequencing (mNGS) of the bronchoalveolar lavage fluid identified 926 DNA sequence reads and 195 RNA sequence reads corresponding to M. tuberculosis complex, respectively. mNGS of blood identified 48 DNA sequence reads corresponding to M. tuberculosis. There was no sequence read corresponding to other potential pathogens. She was initially administered standard ATT together with a low dose of methylprednisolone (40 mg/day). However, her condition deteriorated rapidly with high fever, acute respiratory distress syndrome, pancytopenia, and hyperferritinemia. Bone marrow smears showed hemophagocytosis. And caseating tuberculous granulomas were found in the placenta. A diagnosis of disseminated TB-associated HLH was made. Along with the continuation of four drug ATT regimen, therapy with a higher dose of methylprednisolone (160 mg/day) combined with immunoglobulin and plasma exchange was managed. The patient's condition improved, and she was discharged on day 19. Her condition was good at follow-up with the continuation of the ATT. Conclusions: Clinicians encountering patients with suspected TB accompanied by unexplainable inflammation not responding to ATT should consider complications with HLH. Timely administration of ATT combined with corticosteroids may result in a favorable outcome.

Effect of recombinant Panton-Valentine leukocidin in vitro on apoptosis and cytokine production of human alveolar macrophages.

Panton-Valentine leukocidin (PVL) is associated with rare cases of necrotizing pneumonia that occur in otherwise healthy individuals. Human alveolar macrophages (HAMs) are major effector cells in host defense against infections. However, the impact of PVL on HAMs is uncertain. We evaluated the role of PVL in cytotoxicity and production of inflammatory cytokines secreted by HAMs. HAMs were purified from bronchoalveolar lavage fluid. Recombinant PVL (rPVL) was used in the study to interfere with HAM apoptosis and cytokine production in vitro. Hoechst 33342 fluorescence staining, transmission electron microscopy examination, and flow cytometry indicated that rPVL (10 nmol/L) treatment resulted in HAMs with markedly apoptotic characteristics, and HAMs treated with rPVL at 100 nmol/L showed clear indication of necrosis. A treatment of rPVL at 10 nmol/L elicited the secretion of IL-10 by HAMs relative to untreated control cells, but there was a slight decrease in the constitutive secretion of tumor necrosis factor (TNF)-alpha. Our results indicate that PVL-treated samples decreased HAM viability, leading to apoptosis at low concentrations and necrosis at high concentrations. In addition, PVL-treated cells released increased amounts of IL-10 and decreased amounts of TNF-alpha under apoptosis-inducing concentrations. Therefore, we speculated that PVL could play a negative role in HAM function at lower concentrations.

[Analysis of risk factors related to mortality of patients with community-acquired pneumonia due to methicillin-resistant Staphylococcus aureus].

OBJECTIVE: To describe the clinical features of reported cases of community-acquired pneumonia (CAP) due to methicillin-resistant Staphylococcus aureus (MRSA), and to evaluate the risk factors related to outcome. METHODS: A systematic search of databases from January 1995 to December 2009 was performed. Baseline characteristics of survivors and non-survivors in the hospital were compared with the chi2 test for categorical variables. Variables with P<0.2 were entered in Logistic regression. Survival analysis was estimated by the Kaplan-Meier method according to use of antimicrobials inhibiting toxin production. RESULTS: Fifty-two articles were identified reporting data on 74 patients, with 41.1% of total mortality, short duration of symptom onset to death [(6.1+/-11.0) days], and prolonged hospital admissions [(28.6+/-29.1) days]. Logistic regression analysis showed that influenza like symptoms (P=0.04), hemoptysis (P<0.01), leucopenia (P<0.01) were the risk factors associated with death, and using clindamycin or linezolid which could inhibit the Panton-Valentine leukocidin (PLV, P<0.01) was the factor associated with survival. Kaplan-Meier analysis indicated that the antibiotic therapies inhibiting toxin production were associated with improved outcome in these cases (chi2=21.59, P<0.01). CONCLUSION: CAP due to MRSA is a severe disease with significant lethality. Empiric therapy of severe CAP with flu-like symptoms, hemoptysis and leucopenia should include coverage for MRSA. Targeted treatment with antimicrobials inhibiting toxin production appear to be more appropriate selection.

Cytomegalovirus Infection in an Adult Patient With Neuromyelitis Optica and Acute Hemorrhagic Rectal Ulcer: Case Report and Literature Review.

Background: Previous infectious or inflammatory events may be involved in the pathogenesis of neuromyelitis optica (NMO), potentially by triggering an autoimmune response. Cytomegalovirus (CMV)-related NMO (CMV-NMO) is rarely reported. Acute hemorrhagic rectal ulcer (AHRU) is a rare disease with a largely unknown pathogenesis. Herein, we reported a co-NMO and AHRU case associated with CMV infection. In addition, we review previously reported cases of CMV-NMO and CMV-AHRU. Case presentation: A 40-year-old female diagnosed with aquaporin4 (AQP4)-IgG+ NMO and a poor response to high-dose intravenous methylprednisolone and immunoglobulin, followed by three rounds of plasma exchange was transferred to Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. She developed repeated acute lower gastrointestinal hemorrhage from the third day of admission. Abdominal computed tomography angiography (CTA) and interventional angiography did not detect any bleeding vessel. Bedside colonoscopy revealed a large ulcer-like lesion at 10 cm above the anus. Rectal biopsy pathology confirmed a CMV infection on day 23 post-admission, and cerebrospinal fluid (CSF) pathogen gene sequencing detected CMV gene copies on day 25 post-admission. After 2 weeks of treatment with ganciclovir and sodium phosphinate, the patient's lower gastrointestinal bleeding stopped, and her limb muscle strength and visual acuity gradually improved. After 4 weeks of antiviral therapy, colonoscopy showed that the intestinal wall of the original lesion was smooth. Hematoxylin and eosin (HE) staining and immunohistochemistry (IHC) of a biopsy specimen was negative for CMV, her right eye vision was normal, and limb muscle strength had recovered. Serum AQP4-IgG was negative, and lesions on brain magnetic resonance imaging (MRI) manifested shrinkage. Conclusions: The benefits of antiviral therapy remain unclear; however, clinicians should be aware of the possibility of CMV-related NMO, if NMO was refractory to high-dose intravenous methylprednisolone, immunoglobulin, and plasma exchange. Moreover, clinicians should consider the possibility of CMV-related AHRU when recurrent acute lower gastrointestinal bleeding occurs in a patient.

Serum human epididymis protein 4 concentrations are associated with severity of patients with pulmonary tuberculosis.

BACKGROUND: Human epididymis protein 4 (HE4) has been recognized as a biomarker which elevated in various diseases. The aim of this study was to evaluate the value of serum HE4 in pulmonary tuberculosis (PTB). METHODS: Serum HE4 concentrations were determined in 127 PTB, 88 chronic bronchitis (CHB), and 105 healthy control subjects by chemiluminescent microparticle immunoassay. Receiver operating characteristic (ROC) curves and Spearman's correlation analysis were performed for investigating value of HE4. RESULTS: Serum HE4 concentrations were significantly increased in PTB (62.8 pmol/L, IQR 45.8-90.7), compared with that of CHB (50.2 pmol/L, IQR 42.3-64.3, P = 0.0002) and normal control (35.4 pmol/L, IQR 31.1-42.9, P < 0.0001). ROC curve suggested that the AUC of HE4 used to discriminate PTB from CHB was 0.647 (95% CI, 0.574-0.719), with the cutoff value, sensitivity, specificity, PPV, and NPV at 71.9 pmol/L, 0.417, 0.852, 0.672 and 0.543, respectively. Meanwhile, compared with mild to moderated PTB, the levels of HE4 in advanced PTB were significantly elevated (75.8 vs. 57.7 pmol/L, P = 0.0052). What's more, the levels of HE4 in PTB were found to be significantly associated with the albumin, CRP, and cavity (r = -0.2996, P = 0.0006, r = 0.265, P = 0.0026, r = 0.4699, P < 0.0001, respectively). CONCLUSIONS: Elevated serum HE4 concentration could be used as a biomarker for the diagnosis and assessment of disease severity in PTB.

Chronic exposure to exogenous matrilysin induces chemoresistance and enhances Bcl-2 expression in A549 lung adenocarcinoma cells.

Matrix metalloproteinase (MMP) family member matrilysin (matrilysin) has been indicated to induce apoptosis-resistance and chemoresistance. The purpose of current study was to investigate the potential capacity of induction cisplatin-resistance upon the unremitting exposure to exogenic matrilysin. At the same time, the expressions of apoptosis-related genes were examined to clarify the underlying mechanisms. A549 lung adenocarcinoma cells was used to establish our chronic exposure models. The viability of A549 lung adenocarcinoma cells was determinated by MTT and the apoptosis was assessed by Hoechst 33342 staining and Annexin V-FITC/PI apoptosis kit. The expressions of apoptosis-relative genes were evaluated by flow cytometry, immunocytochemistry staining and real-time quantitative RT-PCR, respectively. Overall, chronic exposure to crescenting level of exogenous matrilysin (10, 50, 100, 200 ng/ml) did not significantly alter the growth rates of A549 cells. However, a certain range of matrilysin might protect tumor cells from cisplatin-medicated death. The underlying mechanism may due to the Bcl-2 overexpression and imbalance in the ratio of Bcl-2/Bax. Our results offer a potential mechanism to explain the impact of matrilysin on apoptosis and provide new insights into the profound mechanisms of acquired cisplatin-resistance. Further researches are highly suggestive of this association which has great clinical implications.

Pulmonary cryptococcosis in non-AIDS patients.

PURPOSE: To clarify the clinical features and imaging characteristics of non-AIDS patients with pulmonary cryptococcosis. METHODS: We retrospectively collected 15 HIV-negative patients with pathology-proved pulmonary cryptococcosis from Sep 1992 to Jan 2008. Their medical records and radiological data were reviewed and analyzed. RESULTS: Only one patient was asymptomatic.Thirteen patients were immunocompetent and two were immunosuppressed. Three patients had associated cryptococcosis meningitis. The most common radiographic abnormalities were multiple pulmonary nodules or masses, seen in 8 and 5 cases of patients respectively. 14 patients received specific therapy for Cryptococcus neoformans. Two patients died. In the 11 patients with isolated pulmonary cryptococcosis, treatment consisted of fluconazole alone (n=7), in combination with amphotericin B (n=2), and both 5-flucytosine and amphotericin B (n=2). For the other 2 patients with cryptococcosis meningitis, one was treated with amphotericin B alone and the other with fluconazole combined with amphotericin B and 5-flucytosine. CONCLUSIONS: Non-AIDS patients might also susceptible to cryptococcosis infection. Histological examination is the principal method of diagnosis. The most common CT findings are solitary or multiple nodules with or without cavitation in the subpleural areas of the lung.

[The effect of recombinant panton-valentine leukocidin on the production of cytokines by human alveolar macrophages].

OBJECTIVE: To investigate the effect of recombinant panton-valentine leukocidin (rPVL) on the regulation of human alveolar macrophage CD14 and IL-10 and TNF-alpha. METHODS: Human alveolar macrophages (AM) were purified and cultured from bronchoalveolar lavage fluid. Each sample was divided into groups according to different concentrations and exposure times of rPVL. Semi-quantitative RT-PCR was used to evaluate the CD14 mRNA levels and Double-antibody-sandwich-ELISA was used to measure the IL-10 and TNF-alpha levels in AM cultures. RESULTS: CD14 mRNA decreased after rPVL treatment in time-and concentration dependent manners. There were no statistically significant differences in CD14 mRNA among the blank control groups (F = 1.708, P > 0.05). CD14 mRNA in the T6N10 group and the T6N100 group( T = time in hours, N = concentration of rPVL/nmol/L) decreased as compared to the T6N0 group (t = 4.132, 6.818, both P < 0.001), and that in the T24N10 group and the T24N100 group also decreased as compared to the T24N0 group (t = 7.401, 11.415, both P < 0.001), indicating that the expression of CD14 was downregulated by rPVL treatment. There were also statistically significant differences in CD14 mRNA between T6N10 and T24N10 groups, T6N100 and T24N100 groups (t = 4.692, 6.019, both P < 0.001), T6N10 and T6N100 groups, T24N10 and T24N100 groups (t = 2.686, 4.014, P < 0.01 respectively), indicating that the expression of CD14 decreased as the treatment time and the concentration of rPVL increased. The IL-10 concentrations of the T24N10 and T24N100 groups increased as compared to the T24N0 group (t = 4.036, 3.941, both P < 0.01) in time-dependent and concentration-dependent manners with rPVL treatment. The TNF-alpha concentration of the T24N10 group decreased while that of the T24N100 group increased as compared to the T24N0 group (t = 2. 824, 8. 468, both P < 0.01, respectively), indicating that a lower concentration of rPVL inhibited TNF-alpha release while a higher concentration of rPVL induced release of TNF-alpha. CONCLUSION: The results suggest that rPVL could reduce the expression of CD14 and induce disordered release of anti-inflammatory and proinflammatory cytokines by AMs, which may be one of the important mechanisms underlying the high mortality of infection with PVL-positive Staphylococcus aureus.