Advances in severe community-acquired pneumonia No abstract available

Spreading of extended-spectrum β-lactamase-producing Escherichia coli ST131 and Klebsiella pneumoniae ST11 in patients with pneumonia: a molecular epidemiological study Background: Extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) are the important pathogens causing pneumonia. This study aimed to investigate the clinical characteristics and molecular epidemiology of ESBL-producing E. coli and K. pneumoniae causing pneumonia at a large teaching hospital in China. Methods: We collected patient's clinical data and ESBL-producing E. coli and K. pneumoniae strains causing pneumonia (from December 2015 to June 2016) at a hospital in Wuhan. The susceptibilities, multi-locus sequence typing, homologous analysis, ESBL genes by polymerase chain reaction and sequencing were determined. Results: A total of 59 ESBL-producing strains (31 E. coli and 28 K. pneumoniae) isolated from patients with pneumonia were analyzed. The majority of strains were isolated from patients were with hospital-acquired pneumonia (37/59, 62.7%), followed by community-acquired pneumonia (13/59, 22.0%), and ventilator-related pneumonia (9/59, 15.3%). The E. coli ST131 (9 isolates, 29.0%) and K. pneumoniae ST11 (5 isolates, 17.9%) were the predominant sub-types. The most prevalent ESBL gene was CTX-M-14, followed by SHV-77, CTX-M-3, SHV-11, and CTX-M-27. At least 33 (55.9%) of the ESBL-producing strains carried two or more ESBL genes. The ISEcp1 and IS26 were found upstream of all blaCTX-M (CTX-Ms) and of most blaSHV (SHVs) (57.6%), respectively. Moreover, three ESBL-producing K. pneumoniae ST11 strains which were resistant to carbapenems carried the blaNDM-1 and blaKPC-2, two of which also bearing blaOXA-48 were resistant to all antibiotics (including Tigecycline). Conclusions: Hospital-acquired pneumonia is more likely correlated with ESBL-producing E. coli and K. pneumoniae. ESBL-producing E. coli ST131 and multi-drug resistance ESBL-producing, as well as New Delhi metallo-β-lactamase-1 (NDM-1) and Klebsiella pneumoniae carbapenemases-2 (KPC-2) bearing K. pneumoniae ST11 are spreading in patients with pneumonia in hospital.

Quantitative computed tomography measurement of cross-sectional area of small pulmonary vessels in asthmatic patients Background: Cross-sectional area (CSA) for small pulmonary vessels is considered a parameter of pulmonary vessel alterations in patients with chronic obstructive pulmonary disease. This study was to evaluate the correlation of CSA with airflow obstruction parameters in asthma. Furthermore, we aimed to measure the difference in vascular alteration between asthma phenotypes and evaluate its relation with cytokine levels. Methods: We consecutively enrolled 20 adult asthmatic patients (13 women: age range, 26–80 years) and 20 healthy controls (8 women: age range, 23–61 years) from Peking University Third Hospital. Total CSA <5 mm2 (CSA<5) was measured with 64-slice spiral computed tomography, and the percentage CSA <5 for the lung area (%CSA<5) was calculated. Data were corrected for body surface area to obtain sixth-generation airway luminal diameter (LDcor), luminal area (Aicor), and airway wall thickness, and airway wall area percentage (WA%) was calculated. Enzyme-linked immunosorbent assay was used to detect the expression of leptin, total immunoglobulin E, periostin, and transforming growth factor β1 in serum and matrix metalloproteinase 9 in induced sputum supernatant of asthmatic patients. The differences in %CSA<5 between subgroups were assessed by independent samples Student's t test, and Spearman correlation analysis was used to analyze the correlation of %CSA<5 with clinical indexes and inflammatory cytokine levels. Results: Patients with asthma and controls did not differ in %CSA<5. In asthma patients, %CSA<5 was lower with initial onset age ≤12 years old, airflow restriction and uncontrolled Global Initiative for Asthma classification (all P < 0.05). Moreover, it was positively correlated with forced vital capacity ratio in 1 s (FEV1)/forced expiratory volume ratio, FEV1%, LDcor, Aicor, and serum leptin level (all P < 0.05) and negatively with total lung WA% (P = 0.007). Conclusions: %CSA<5 of pulmonary small vessels was well correlated with airflow limitation indexes and sixth-generation airway parameters. It has certain significance in predicting the clinical control of asthma.

Determinants of prognosis in Talaromyces marneffei infections with respiratory system lesions Background: Little study has investigated the differences between Talatomyces marneffei (T. marneffei) respiratory infection and tuberculosis and the prognostic factors of such infection. This study investigated the characteristics and prognostic factors of T. marneffei infections with respiratory lesions and the causes of misdiagnosis. Methods: Clinical characteristics and prognoses of patients with T. marneffei infections with respiratory system lesion were investigated. T. marneffei diagnosis followed isolation from clinical specimens using standard culture, cytology, and histopathology. Survival curves were estimated by using Kaplan-Meier analysis, with log-rank test to compare differences in survival rates between groups. Univariate and multivariate Cox regression analyses were also performed to assess significant differences in clinical characteristics of overall survival. Results: Of 126 patients diagnosed with T. marneffei infections, 63 (50.0%) had T. marneffei respiratory system infections; 38.1% (24/63) were misdiagnosed as having tuberculosis. Human immunodeficiency virus (HIV) infection, CD4/CD8 < 0.5, percentage of CD4+ T cells <42.8%, and length of time from onset to confirmation of diagnosis >105 days were potential risk factors for poor prognoses. Length of time from onset to confirmation of diagnosis persisted as an independent predictor of all-cause mortality in multivariate analysis (odds ratio: 0.083, 95.0% confidence interval: 0.021–0.326, P < 0.001). However, the size of the lung lesions, dyspnea, thoracalgia, mediastinal lymphadenopathy, and pleural effusion did not significantly predict overall survival. There was no significant difference in prognosis according to the type of treatment. Conclusions: T. marneffei infections involving the respiratory system are common. The critical determinants of prognosis are HIV infection, CD4/CD8, percentage of CD4+ T cells, type of treatment, and the time range from onset to confirmation of diagnosis. Rapid and accurate diagnosis is crucial for improving prognosis.

Quantitative autonomic function test in differentiation of multiple system atrophy from idiopathic Parkinson disease Background: Differential diagnosis of idiopathic Parkinson disease (IPD) and multiple system atrophy-Parkinson type (MSA-P) is challenging since they share clinical features with parkinsonism and autonomic dysfunction. To distinguish MSA-P from IPD when the symptoms are relatively mild, we investigated the usefulness of the quantitative fractionalized autonomic indexes and evaluated the correlations of autonomic test indexes and functional status. Methods: Thirty-six patients with parkinsonism (22 with IPD and 14 with MSA-P) in Soonchunhyang University Bucheon Hospital from February 2014 to June 2015 were prospectively enrolled in the study. We compared fractionalized autonomic indexes and composite autonomic scoring scale between patients with IPD and MSA-P with Hoehn and Yahr (H&Y) score ≤3. Parasympathetic indexes included expiratory/inspiratory ratio during deep breathing, Valsalva ratio (VR), and regression slope of systolic blood pressure (BP) in early phase II (vagal baroreflex sensitivity) during Valsalva maneuver. Sympathetic adrenergic indexes were pressure recovery time (PRT) and adrenergic baroreflex sensitivity (BRSa) (BP decrement associated with phase 3 divided by the PRT), sympathetic index 1, sympathetic index 3, early phase II mean BP drop, and pulse pressure reduction rate. Additionally, we compared the unified multiple system atrophy rating scale (UMSARS) and H&Y scores and the autonomic indexes in all patients. Results: PRT was significantly different between the IPD and MSA-P groups (P  = 0.004) despite the similar BP drop during tilt. Cut-off value of PRT was 5.5 s (sensitivity, 71.4%; specificity, 72.7%). VR (r = −0.455, P = 0.009) and BRSa (r = −0.356, P = 0.036) demonstrated a significant correlation with UMSARS and H&Y scores. Conclusions: Among the cardiovascular autonomic indexes, PRT can be a useful parameter in differentiating the early stage of MSA-P from that of IPD. Moreover, VR, and BRSa may be the optimal indexes in determining functional symptom severity.

Long-term follow-up of auditory performance and speech perception and effects of age on cochlear implantation in children with pre-lingual deafness Background: The development of auditory and speech perception ability of children with hearing loss is affected by many factors after they undergo cochlear implantation (CI). Age at CI (CI age) appears to play an important role among these factors. This study aimed to evaluate the development of auditory and speech perception ability and explore the impact of CI age on children with pre-lingual deafness present before 3 years of age. Methods: Two hundred and seventy-eight children with pre-lingual deafness (176 boys and 102 girls) were included in this study, and the CI age ranged from 6 to 36 months (mean age, 19 months). Categorical auditory performance (CAP) was assessed to evaluate auditory ability, and the speech intelligibility rating was used to evaluate speech intelligibility. The evaluations were performed before CI and 1, 3, 6, 12, 18, 24, 36, 48, and 60 months after CI. Results: The auditory ability of the pre-lingually hearing-impaired children showed the fastest development within 6 months after CI (k = 0.524, t = 30.992, P < 0.05); then, the progress started to decelerate (k = 0.14, t = 3.704, P < 0.05) and entered a plateau at the 24th month (k = 0.03, t = 1.908, P < 0.05). Speech intelligibility showed the fastest improvement between the 12th and 24th months after CI (k = 0.138, t = 5.365, P < 0.05); then, the progress started to decelerate (k = 0.026, t = 1.465, P < 0.05) and entered a plateau at the 48th month (k = 0.012, t = 1.542, P < 0.05). The CI age had no statistical significant effect on the auditory and speech abilities starting at 2 years after CI (P > 0.05). The optimal cutoff age for CI was 15 months. Conclusions: Within 5 years after CI, the auditory and speech ability of young hearing-impaired children continuously improved, although speech development lagged behind that of hearing. An earlier CI age is recommended; the optimal cutoff age for CI is at 15 months.

Outcomes of intermediate-risk to high-risk stage I endometrial cancer: 10-year clinical experiences of using in-house multi-channel applicators in a single center Background: There are only very few reports on clinical outcomes using multi-channel applicators (MCA) for patients with endometrial cancer (EC) in China. We aimed to evaluate the clinical experience of treating intermediate-risk (IR) to high-risk (HR) stage I EC using in-house made multi-channel applicators (IH-MCA) in a single institution. Methods: Three hundred and ninety patients with stage I IR to HR EC were treated with hysterectomy and adjuvant radiotherapy from 2003 to 2015. All patients received post-operative vaginal cuff brachytherapy (VBT) alone or as a boost after external beam radiotherapy (EBRT). The prescriptions were 500 cGy per fraction for a total of 5 to 6 fractions with brachytherapy alone or 400 to 600 cGy per fraction for 2 to 3 fractions if it was combined with EBRT. Two types of applicators including a traditional rigid IH-MCA and a recent model custom-made with 3 dimension printing technology were used for treatment. The Kaplan-Meier method was used to calculate survival rate. Results: Follow-up rate was 92.8% and the median follow-up time was 48 months (range 4–172 months). The 5-year overall survival (OS), progression-free survival, local recurrence, and distant metastasis rates for all patients were 96.3%, 92.1%, 2.9%, and 4.8% respectively. Two patients had isolated relapse in vagina outside the irradiated volume. The univariate and multivariate analysis showed that age and grade were the prognostic factors correlated with OS (hazard ratio: 0.368, 95% confidence interval [CI]: 0.131–1.035, P = 0.048; hazard ratio: 0.576, 95% CI: 0.347–0.958, P = 0.026,). Conclusions: For patients with IR to HR stage I EC, adjuvant VBT alone or in combination with EBRT using IH-MCA led to excellent survival and recurrence rates. Age and grade were the prognostic factors correlated with OS.

Role of p300 in the pathogenesis of Henoch-Schonlein purpura nephritis and as a new target of glucocorticoid therapy in mice Background: Henoch-Schonlein purpura nephritis (HSPN) is a very common secondary kidney disease of childhood. Its pathogenesis and the treatment mechanism of glucocorticoid have not been fully elucidated. The aim of this study was to determine the relationship between p300 and the pathogenesis, glucocorticoid therapy in mice with HSPN, respectively. Methods: Forty-eight C57BL/6N male mice, weighing 18 to 20 g, were selected (3–4 weeks old, n = 8 per group). The mice in the normal control group (Group I) were given normal solvent and the HSPN model group (Group II) were given sensitizing drugs. The mice in Group III were injected intraperitoneally with dexamethasone after being given sensitizing drugs. Meanwhile, mice in Groups IV, V and VI with conditional knockout of p300 were also given normal solvent, sensitizing drugs and dexamethasone. The levels of serum IgA, creatinine, and circulating immune complex (CIC) concentrations, 24 h urinary protein and urinary erythrocyte in C57 wild mice, and p300 conditional knockout mice in each group were measured. The expression of p300 in renal tissues and the expression of glucocorticoid receptor (GR) α and β, transforming growth factor (TGF)-β1, and activator protein (AP)-1 after dexamethasone treatment were determined by real-time polymerase chain reaction and Western blotting. Results: Compared with the normal solvent control group (Group I), the expression of p300 mRNA in the model group (Group II) was significantly up-regulated. Western blotting further confirmed the result. Urinary erythrocyte count, 24 h urinary protein quantification, serum IgA, CIC, and renal pathologic score in Group V were distinctly decreased compared with non-knockout mice in Group II (9.7 ± 3.8 per high-power field [/HP] vs. 18.7 ± 6.2/HP, t = 1.828, P  = 0.043; 0.18 ± 0.06 g/24 h vs. 0.36 ± 0.08 g/24 h, t = 1.837, P  = 0.042; 18.78 ± 0.85 mg/mL vs. 38.46 ± 0.46 mg/mL, t = 1.925, P  = 0.038; 0.80 ± 0.27 μg/mL vs. 1.64 ± 0.47 μg/mL, t = 1.892, P  = 0.041; 7.0 ± 0.5 vs. 18.0 ± 0.5, t = 1.908, P  = 0.039). Compared with non-knockout mice (Group III), the level of urinary erythrocyte count and serum IgA in knockout mice (Group VI) increased significantly after treatment with dexamethasone (3.7 ± 0.6/HP vs. 9.2 ± 3.5/HP, t = 2.186, P  = 0.024; 12.38 ± 0.26 mg/mL vs. 27.85 ± 0.65 mg/mL, t = 1.852, P  = 0.041). The expression level of GRα was considerably increased in the knockout group after dexamethasone treatment compared with non-knockout mice in mRNA and protein level (t = 2.085, P  = 0.026; t = 1.928, P  = 0.035), but there was no statistically significant difference in the expression level of GRβ between condition knockout and non-knockout mice (t = 0.059, P  = 0.087; t = 0.038, P  = 1.12). Furthermore, the expression levels of glucocorticoid resistance genes (AP-1 and TGF-β1) were notably increased after p300 knockout compared with non-knockout mice in mRNA and protein level (TGF-β1: t = 1.945, P  = 0.034; t = 1.902, P  = 0.039; AP-1: t = 1.914, P  = 0.038; t = 1.802, P  = 0.041). Conclusions: p300 plays a crucial role in the pathogenesis of HSPN. p300 can down-regulate the expression of resistance genes (AP-1 and TGF-β1) by binding with GRα to prevent further renal injury and glucocorticoid resistance. Therefore, p300 is a promising new target in glucocorticoid therapy in HSPN.

Protective effect of Saccharomyces boulardii on intestinal mucosal barrier of dextran sodium sulfate-induced colitis in mice Background: The effect and mechanism of Saccharomyces boulardii (Sb) in inflammatory bowel disease are unclear. The objective of the study was to evaluate the impact of Sb on intestinal mucosal barrier and intestinal flora in a colitis mouse model. Methods: Forty C57BL/6J male mice were randomly assigned to five groups: normal control group (A), pathologic control group (B), Sb treatment group (C), mesalazine treatment group (D), and Sb combined with mesalazine treatment group (E). Colitis was induced by the addition of 2.5% (wt/vol) dextran sodium sulfate (DSS) in the drinking water ad libitum for 7 days. The general condition, weight change, stool property, and bloody stool level of mice were observed to evaluate the disease activity index. The expression of zona occludens-1 (ZO-1) and occludin in intestinal tissue were measured by immunohistochemistry. The level of tumor necrosis factor-α (TNF-α) and interleukin (IL)-8 in plasma was measured by enzyme linked immunosorbent assay. Inter-cellular tight junctions were observed by transmission electron microscopy. The feces and intestinal contents were collected sterilely, and intestinal flora was analyzed by 16S rRNA sequencing. Results: Compared with group B, Sb reduced the disease activity index and histological score of group C (disease activity index: group B 2.708 ± 0.628, group C 1.542 ± 0.616, PBC = 0.005; histological score: group B 9.875 ± 3.271, group C 4.750 ± 1.832, PBC = 0.005) in DSS-induced colitis in mice. Sb exerted a protect effect on the expression of ZO-1 (group B 2.075 ± 1.176, group C 4.225 ± 1.316, PBC = 0.019) and occludin (group B 2.200 ± 0.968, group C 3.525 ± 1.047, PBC = 0.023). Compared with group B, Sb decreased the level of TNF-α and IL-8 of group C (TNF-α: group B 716.323 ± 44.691 ng/L, group C 521.740 ± 90.121 ng/L, PBC = 0.001; IL-8: group B 128.992 ± 11.475 pg/mL, group C 106.283 ± 15.906 pg/mL, PBC = 0.012). Treatment with Sb preserved the tight junctions and ameliorated microvilli and inter-cellular space. Treatment with Sb also showed its own characteristics: a higher percentage of Bacteroidetes and a lower percentage of Firmicutes, with significant differences or a significant trend. The proportion of the S24-7 family was increased significantly in the Sb treatment group. Conclusions: Sb shows an anti-inflammatory effect and has a protective effect on the intestinal mucosal mechanical barrier. Sb may up-regulate the abundance of family S24-7 specifically, and maybe a mechanism underlying its function.

Analysis of nickel distribution by synchrotron radiation X-ray fluorescence in nickel-induced early- and late-phase allergic contact dermatitis in Hartley guinea pigs Background: Nickel-induced allergic contact dermatitis (Ni-ACD) is a global health problem. More detailed knowledge on the skin uptake of haptens is required. This study aimed to investigate the penetration process and distribution of nickel in skin tissues with late phase and early phase of Ni-ACD to understand the mechanisms of metal allergy. Methods: Forty Hartley guinea pigs were divided into four groups according to the NiSO4 sensitizing concentration and the NiSO4 challenged concentration: the 5% NiSO4-group, 5% to 10% (sensitization-challenge; late phase group); 10% NiSO4-group, 10% to 10% (sensitization-challenge; early-phase group); and the positive and negative controls. Pathological biopsies were performed on each group. The depth profile of nickel element concentration in the skin of guinea pigs was detected by synchrotron radiation micro X-ray fluorescence spectroscopy (SR-μ-XRF) and micro X-ray absorption near-edge spectroscopy (μ-XANES). Results: In each section, the nickel element concentration in both the 5% NiSO4-group and 10% NiSO4-group was significantly higher than that in the negative control group. In the upper 300-μm section of skin for the early phase group, the nickel element concentration was significantly higher than that in the lower section of skin. In deeper sections (>200 μm) of skin, the concentration of nickel in the early phase group was approximately equal to that in the late phase group. The curve of the late phase group was flat, which means that the nickel element concentration was distributed uniformly by SR-μ-XRF. According to the XANES data for the 10% NiSO4 metal salt solution, structural changes occurred in the skin model sample, indicating that nickel was not present in the Ni2+ aqueous ionic state but in the nickel-binding protein. Conclusions: This study showed that the distribution of the nickel element concentration in ACD skin tissue was different between the early phase and late phase groups. The nickel element was not present in the Ni2+ aqueous ionic state but bound with certain proteins to form a complex in the stratum corneum in ACD model tissue.