Ciliated muconodular papillary tumors (CMPTs) are a recently categorized benign or low‐grade malignant neoplasm that develops in the peripheral lung. Only about 40 cases have been reported to date, ...and the clinicopathological characteristics have yet to be defined in detail. Here, we present four cases of CMPTs with a focus on their immunohistochemical profiles and driver gene mutations. These tumors were a papillary proliferation of a mixture of ciliated, mucous, and basal cells located in the peripheral lung. Ciliated, mucous and basal cells were positive for TTF‐1 when using the clone SPT24, but negative for HNF‐4α. Basal cells were positive for p40. Mucous cells in some tumors were positive for MUC5AC and MUC6. The Ki‐67 index was less than 5%, and strong expression of p53 was not detected. Three of the four tumors had a BRAF (V600E) driver mutation, an EGFR (del E746‐T751/S752V) driver mutation, or driver mutations in both EGFR (E709G) and KRAS (G12V). These mutation types are rare for any histological type of lung cancer. The present results confirmed that CMPT is a neoplasm with immunohistochemical features and driver gene mutations that are distinct from those of common lung tumors.
We investigated the significance of MUC21 in EGFR-mutated lung adenocarcinoma (LADC). Two-hundred forty-one surgically resected LADCs (116 EGFR-mutated and 125 wild-type tumors) were examined for ...immunohistochemical expression of MUC21 protein. A polyclonal antibody and two monoclonal antibodies (heM21C and heM21D) that bind differentially glycosylated MUC21 epitopes were used, and MUC21 proteins detected by these antibodies were named MUC21P, MUC21C, and MUC21D, respectively. MUC21 mRNA levels were semi-quantified and classified into "high" and "low". Among the immunohistochemical expression detected by three different antibodies, high expressors tended to be related to EGFR mutations. The three varieties of the immunohistochemical expressions were related to different histological elements in the EGFR-mutated LADCs. Either MUC21P or MUC21C high expressors had a higher proportion of lepidic elements with low papillary structure and micropapillary elements. MUC21D high expressors had a significantly higher proportion of micropapillary elements (Mann-Whitney test P ≤0.0001). Furthermore, MUC21D high expressors showed high incidence of lymphatic canal invasion and lymph node metastasis (Pearson x2 test, P = 0.0021, P = 0.0125), and a significantly higher recurrence rate (5-year recurrence-free survival 50.7% vs. 73.8%, log-rank test P = 0.0495). MUC21 proteins with a specific glycosylation status may be involved in the progression of EGFR-mutated LADCs, particularly at the stage where tumors are transforming from pure lepidic to micropapillary through low papillary lepidic lesions.
Production of α1,3-Galactosyltransferase: Deficient Pigs Phelps, Carol J.; Koike, Chihiro; Vaught, Todd D. ...
Science (American Association for the Advancement of Science),
01/2003, Letnik:
299, Številka:
5605
Journal Article
Recenzirano
Odprti dostop
The enzyme α1,3-galactosyltransferase (α1,3GT or GGTA1) synthesizes α1,3-galactose (α1,3Gal) epitopes (Galα1,3Galβ1,4GlcNAc-R), which are the major xenoantigens causing hyperacute rejection in ...pig-to-human xenotransplantation. Complete removal of α1,3Gal from pig organs is the critical step toward the success of xenotransplantation. We reported earlier the targeted disruption of one allele of the α1,3GT gene in cloned pigs. A selection procedure based on a bacterial toxin was used to select for cells in which the second allele of the gene was knocked out. Sequencing analysis demonstrated that knockout of the second allele of the α1,3GT gene was caused by a T-to-G single point mutation at the second base of exon 9, which resulted in inactivation of the α1,3GT protein. Four healthy α1,3GT double-knockout female piglets were produced by three consecutive rounds of cloning. The piglets carrying a point mutation in the α1,3GT gene hold significant value, as they would allow production of α1,3Gal-deficient pigs free of antibiotic-resistance genes and thus have the potential to make a safer product for human use.
Pseudomonas aeruginosa, responsible for serious nosocomial-acquired infections, possesses intrinsic antibiotic resistance mechanisms and commonly exhibits multidrug resistance. Here, we report the ...evolving resistance profiles of strains isolated from the sputum of a patient being treated for repeated P. aeruginosa infections following cancer resection. Whole genome sequencing of six isolates obtained over a 2-month period revealed two key single nucleotide polymorphisms in the mexR and gyrB genes that affected efflux pump expression and antimicrobial resistance.
Interstitial pneumonia (IP) is a major risk factor for lung adenocarcinoma (LADC). IP-related LADC predominantly develops in the bronchiolar metaplasia lining in honeycomb lesions. Kirsten rat ...sarcoma virus (KRAS) is the most common oncogene mutated in IP-related LADC. The present study examined the metaplastic epithelia in honeycomb lesions for KRAS mutations using digital droplet polymerase chain reaction (ddPCR), a sensitive method used to detect infrequent mutations. Significantly higher KRAS mutation variant allele frequencies (VAFs) were detected in the metaplastic lung epithelia from 13 patients with IP compared with those in 46 non-lesioned lung samples from patients without IP (G12V, P=0.0004, G12C, P=0.0181, and G12A, P=0.0234; Mann Whitney U test). Multivariate analyses revealed that higher KRAS G12V (logistic regression model; P=0.0133, odds ratio=7.11) and G12C (P=0.0191, odds ratio=5.81) VAFs in patients with IP were independent of confounding variables, such as smoking and age. In patients with IP, metaplastic epithelia exhibited significantly higher KRAS G12V and G12C VAFs compared with the non-lesioned counterparts (paired t-test; G12V, P=0.0158, G12C, P=0.0465). These results suggested that IP could increase KRAS mutations and supported the hypothesis that bronchiolar metaplasia could be a precursor for IP-related LADC.
Objective
To evaluate the long-term effects of comprehensive antibiotic stewardship programs (ASPs) on antibiotic use, antimicrobial-resistant bacteria, and clinical outcomes.
Design
Before–after ...study.
Setting
National university hospital with 934 beds.
Intervention
Implementation in March 2010 of a comprehensive ASPs including, among other strategies, weekly prospective audit and feedback with multidisciplinary collaboration.
Methods
The primary outcome was the use of antipseudomonal antibiotics as measured by the monthly mean days of therapy per 1000 patient days each year. Secondary outcomes included overall antibiotic use and that of each antibiotic class, susceptibility of
Pseudomonas aeruginosa
, the proportion of patients isolated methicillin-resistant
Staphylococcus aureus
(MRSA) among all patients isolated
S. aureus
, the incidence of MRSA, and the 30-day mortality attributable to bacteremia.
Results
The mean monthly use of antipseudomonal antibiotics significantly decreased in 2011 and after as compared with 2009. Susceptibility to levofloxacin was significantly increased from 2009 to 2016 (
P
= 0.01 for trend). Its susceptibility to other antibiotics remained over 84% and did not change significantly during the study period. The proportion of patients isolated MRSA and the incidence of MRSA decreased significantly from 2009 to 2016 (
P
< 0.001 and = 0.02 for trend, respectively). There were no significant changes in the 30-day mortality attributable to bacteremia during the study period (
P
= 0.57 for trend).
Conclusion
The comprehensive ASPs had long-term efficacy for reducing the use of the targeted broad-spectrum antibiotics, maintaining the antibiotic susceptibility of
P. aeruginosa,
and decreasing the prevalence of MRSA, without adversely affecting clinical outcome.
Objectives
To examine the clinical risk factors for death within 30 days of diagnosis of Pseudomonas aeruginosa‐causing bacteremia after a urinary tract infection.
Methods
A total of 62 patients with ...Pseudomonas aeruginosa isolated from both urine and blood at the same episode from January 2009 to December 2016 were enrolled in the present study. We retrospectively investigated clinical risk factors for death by comparison between surviving patients and those who died within 30 days after diagnosis of P. aeruginosa bacteremia. The comparison for risk factors for bacteremia‐related death included 31 categories, such as age, laboratory data, underlying diseases, clinical history, history of surgery, care in the intensive care unit, P. aeruginosa susceptibility to the antibiotics used at the time of bacteremia diagnosis and consultation with urological department.
Results
The study included 48 men and 14 women aged 71.3 ± 10.4 years. Nine patients (14.5%) died of P. aeruginosa bacteremia. Statistical analysis showed that non‐survivors had significantly lower albumin levels than survivors (2.07 ± 0.62 vs 2.62 ± 0.65; P = 0.023). The non‐survivors had significantly higher rates of ventilator use, history of heart disease, septic shock and lower rates of consultation with urological departments after diagnosis (P < 0.05).
Conclusions
Patients with bacteremia complicating urinary infection by P. aeruginosa have a low death rate. Earlier intervention by urologists might improve patients’ outcome. Lower albumin levels, ventilator use, history of heart disease and septic shock are factors associated with higher mortality rate.
Purpose
This study aimed to evaluate the efficacy of an educational intervention on reducing the inappropriate use of oral third-generation cephalosporins, the prevalence of resistant bacteria, and ...clinical outcomes.
Methods
A before-after study was conducted to compare the data for 1 year before and after intervention at a Japanese university hospital. Educational intervention included lectures for all medical staff on oral antibiotics and educational meetings with each medical department. The primary outcome was the use of oral third-generation cephalosporins in inpatients as measured by the monthly median days of therapy (DOTs) per 1000 patient days. Secondary outcomes included the use of each oral antibiotic in inpatients and outpatients, proportion of β-lactamase-nonproducing ampicillin-resistant
Haemophilus influenzae
(BLNAR), penicillin-resistant
Streptococcus pneumoniae
(PRSP) and extended-spectrum β-lactamase producing
Escherichia coli
(ESBLEC), the incidence of hospital-acquired
Clostridioides difficile
infection (HA-CDI), and hospital mortality.
Results
The use of oral third-generation cephalosporins in inpatients was significantly decreased after intervention DOTs (interquartile range): 24.2 (23.5–25.1) vs. 3.7 (0.0–7.1),
P
< 0.001, and the value in outpatients was also decreased significantly. The use of fluoroquinolones and macrolides did not increase after intervention. The proportion of BLNAR, PRSP and ESBLEC did not change significantly during the study period. The incidence of HA-CDI was significantly decreased, and hospital mortality did not change after intervention.
Conclusion
Educational intervention was effective in reducing the use of oral third-generation cephalosporins without increasing the use of broad-spectrum antibiotics and worsening clinical outcome. The prevalence of resistant bacteria did not change during the study period.
Nevi are benign melanocytic tumors, and some nevi are considered to develop into malignant melanomas. Most nevi arise in the skin, but nevi occasionally occur in the conjunctiva, esophageal mucosa, ...or at other sites. Pulmonary melanocytic nevi are extremely rare, and only one case has been reported in the literature. Here, we present a case of pulmonary melanocytic nevus, involving a BRAF gene mutation (V600E), and we discuss the potential significance of this condition as a precursor to pulmonary malignant melanoma.
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