Purpose: Optimal treatment for stage IIIA/N2 non–small cell lung cancer (NSCLC) is controversial. We aimed to assess the efficacy and safety of adjuvant pembrolizumab for stage IIIA/N2 NSCLC completely resected after neoadjuvant concurrent chemoradiation therapy (CCRT). Materials and Methods: In this open-label, single-center, single-arm phase 2 trial, patients with stage IIIA/N2 NSCLC received adjuvant pembrolizumab for up to 2 years after complete resection following neoadjuvant CCRT. The primary endpoint was disease-free survival (DFS). Secondary endpoints included overall survival (OS) and safety. As an exploratory biomarker analysis, we evaluated the proliferative response of blood CD39+PD-1+CD8+ T cells using fold changes in the percentage of proliferating Ki-67+ cells from days 1 to 7 of cycle 1 (Ki-67D7/D1). Results: Between October 2017 and October 2018, 37 patients were enrolled. Twelve (32%) and three (8%) patients harbored EGFR and ALK alterations, respectively. Of 34 patients with programmed cell death ligand 1 assessment, 21 (62%), nine (26%), and four (12%) had a tumor proportion score of < 1%, 1%-50%, and ≥ 50%, respectively. The median follow-up was 71 months. The median DFS was 22.4 months in the overall population, with a 5-year DFS rate of 29%. The OS rate was 86% at 2 years and 76% at 5 years. Patients with tumor recurrence within 6 months had a significantly lower Ki-67D7/D1 among CD39+PD-1+CD8+ T cells than those without (p=0.036). No new safety signals were identified. Conclusion Adjuvant pembrolizumab may offer durable disease control in a subset of stage IIIA/N2 NSCLC patients after neoadjuvant CCRT and surgery.

Parricide, the crime of murdering a parent, accounts for about 5% of all homicides. Filicide is the crime of murdering one's own child. This study aimed to review demographic features and criminal characteristics of individuals who committed parricide and filicide in Republic of Korea (ROK). This study is based on data from the Korea Police Crime Analysis System, from 2006~2013. We assessed the diverse characteristics of both victims and perpetrators. Over the selected period, 381 parents were killed by their children and 230 children were killed by parents in the ROK. Parricides caused by schizophrenic murders accounted for 39.6% of all cases. Moreover, approximately 44.4% of the perpetrators attempted suicide following the maternal filicide. In our findings, psychiatric illness was a very important predictor in parricide, and these further suggest that young mothers with severe mental illness require careful monitoring by mental health support service.
Child ; Crime ; Criminals ; Homicide ; Humans ; Korea ; Mental Health ; Mothers ; Parents ; Police ; Republic of Korea ; Schizophrenia ; Suicide, Attempted

Fibrosing mediastinitis is a rare disease that is characterized by the proliferation of dense fibrous tissue of the mediastinum. The pathogenesis of fibrosing mediastinitis is unknown in most cases. However, histoplasmosis, tuberculosis, autoimmune disease, radiation therapy, and other idiopathic fibroinflammatory diseases have been implicated in some cases. Most clinical features are related to an obstruction or compression of the mediastinal structure. Fibrosing mediastinitis is often progressive and occurs diffusely throughout the mediastinum. We encountered a case of fibrosing mediastinitis of a very focal lesion without evidence of mediastinal involvement. The condition was confirmed by biopsy and graft bypass surgery was performed because of SVC syndrome.
Autoimmune Diseases ; Biopsy ; Histoplasmosis ; Mediastinitis* ; Mediastinum ; Rare Diseases ; Transplants ; Tuberculosis

PURPOSE: Survivin is a member of the inhibitor of apoptosis (IAP) protein family, and it is involved in the regulation of cell division. The over-expression of survivin has been reported to be associated with the parameters for a poor prognosis in most human cancers, including lung, breast, colon, stomach, esophagus, pancreas, etc. In this study, we examined the expression of a member of a novel IAP protein family, survivin, in breast cancer and its association with tumor cell apoptosis and the overall prognosis. METHODS: 80 cases of formalin-fixed paraffin-embedded breast cancer tissue were immunostained with, using polyclonal survivin (Novus Biologicals, Littleton, USA), monoclonal bcl-2 (DAKO, Carpinteria, USA), and monoclonal p53 antibodies (DAKO, Carpinteria, USA). The histochemical method used for the analysis of apoptosis was based on ApopTag. Peroxidase In Situ OligoLigation (ISOL) Apoptosis Detection Kit (CHEMICON International Inc. Temecula, USA). RESULTS: Immunohistochemical analysis showed that cytoplasmic survivin expression was positive in 43 of 80 cases (53.8%) of breast carcinomas and it was positive for 70% of the cases that showed a bcl-2 expression tumors. Statistical analysis revealed that the survivin expression was correlated with lymph node metastasis, the tumor stage, and the histological grade. Although the survivin expression was not correlated with p53 mutations, the survivin positive cases were associated with a bcl-2 expression (p=0.015) and a reduced apoptotic index (p=0.024). On the Cox proportional hazard model analysis, the apoptotic index was not identified as a significant independent predictor of overall survival (p=0.072), although the patients with a low apoptotic index (<0.2%) had a worse survival rates than those patient in the group with a high apoptotic index (> or =0.2%). CONCLUSION: The results suggest that apoptosis inhibition of apoptosis by survivin may be a prognostic parameter for a worse outcome in breast carcinoma patients.
Antibodies ; Apoptosis* ; Breast Neoplasms* ; Breast* ; Cell Division ; Colon ; Cytoplasm ; Esophagus ; Humans ; Lung ; Lymph Nodes ; Neoplasm Metastasis ; Pancreas ; Peroxidase ; Prognosis ; Proportional Hazards Models ; Stomach ; Survival Rate

We conducted this study to compare clinical features, outcomes, and clinical implication of antimicrobial resistance in Klebsiella pneumoniae bacteremia acquired as community vs. nosocomial infection. A total of 377 patients with K. pneumoniae bacteremia (191 community-acquired and 186 nosocomial) were retrospectively analyzed. Neoplastic diseases (hematologic malignancy and solid tumor, 56%) were the most commonly associated conditions in patients with nosocomial bacteremia, whereas chronic liver disease (35%) and diabetes mellitus (20%) were the most commonly associated conditions in patients with community-acquired bacteremia. Bacteremic liver abscess occurred almost exclusively in patients with community-acquired infection. The overall 30-day mortality was 24% (91/377), and the mortality of nosocomial bacteremia was significantly higher than that of community-acquired bacteremia (32% vs. 16%, p<0.001). Of all community-acquired and nosocomial isolates, 4% and 33%, respectively, were extended-spectrum cephalosporin (ESC)-resistant, and 4% and 21%, respectively, were ciprofloxacin (CIP)-resistant. In nosocomial infections, prior uses of ESC and CIP were found to be independent risk factors for ESC and CIP resistance, respectively. Significant differences were identified between community-acquired and nosocomial K. pneumoniae bacteremia, and the mortality of nosocomial infections was more than twice than that of community-acquired infections. Antimicrobial resistance was a widespread nosocomial problem and also identified in community-acquired infections.
Treatment Outcome ; Risk Factors ; Retrospective Studies ; Middle Aged ; Male ; *Klebsiella pneumoniae ; Klebsiella Infections/*drug therapy ; Humans ; Female ; Drug Resistance, Bacterial ; Cross Infection/*drug therapy/mortality ; Community-Acquired Infections/*drug therapy/mortality ; Ciprofloxacin/therapeutic use ; Cephalosporins/therapeutic use ; Bacteremia/*drug therapy/mortality ; Aged, 80 and over ; Aged ; Adult ; Adolescent ; APACHE

BACKGROUND: To identify specific risk factors for Pseudomonas aeruginosa and evaluate the relationship between the mortality rate and P. aeruginosa bacteraemia in bloodstream infections, we compared the clinical features and outcomes of patients with P. aeruginosa bacteremia with the patients with Klebsiella pneumoniae or Enterobacter bacteremia. MATERIALS AND METHODS: A total of 190 patients with P. aeruginosa bacteremia were identified from January 1998 to December 2002 and included in this retrospective analysis. During the same period, 377 patients with K. pneumoniae bacteremia and 183 patients with Enterobacter bacteremia were identified and compared with those with P. aeruginosa bacteremia. RESULTS: Factors associated with P. aeruginosa bacteremia in the multivariate analysis included pneumonia, soft tissue infection, nosocomial acquisition, neutropenia, and prior invasive procedure (All P<0.05). The 30-day mortality rate was 37.9% (72/190) in patients with P. aeruginosa bacteremia, 24.1% (91/377) in those with K. pneumoniae, and 25.7% (47/183) in those with Enterobacter bacteremia (P<0.001). However, in the analysis including patients who had received appropriate initial antimicrobial therapy (n=552), the mortality rate of P. aeruginosa bacteremia was not significantly higher than that of non-pseudomonas bacteremia (28.6% [18/63] vs. 22.5% [110/489]; P=0.282). Inappropriate initial antimicrobial therapy was found to be one of the significant independent predictors of mortality. P. aeruginosa bacteremia as a risk factor for mortality did not reach statistical significance (OR, 1.30; 95% CI, 0.73-2.32; P=0.371), after adjusting for underlying illness and adequacy of antimicrobial therapy. CONCLUSION: An initial empirical antimicrobial coverage of P. aeruginosa should be seriously considered in patients with pneumonia, soft tissue infection, neutropenia, and prior invasive procedure, when gram-negative sepsis was suspected in nosocomial infection.
Bacteremia* ; Cross Infection ; Enterobacter* ; Gram-Negative Bacterial Infections ; Humans ; Klebsiella pneumoniae* ; Klebsiella* ; Mortality ; Multivariate Analysis ; Neutropenia ; Pneumonia ; Pseudomonas aeruginosa* ; Pseudomonas* ; Retrospective Studies ; Risk Factors ; Sepsis ; Soft Tissue Infections ; Treatment Outcome

BACKGROUND: To identify specific risk factors for Pseudomonas aeruginosa and evaluate the relationship between the mortality rate and P. aeruginosa bacteraemia in bloodstream infections, we compared the clinical features and outcomes of patients with P. aeruginosa bacteremia with the patients with Klebsiella pneumoniae or Enterobacter bacteremia. MATERIALS AND METHODS: A total of 190 patients with P. aeruginosa bacteremia were identified from January 1998 to December 2002 and included in this retrospective analysis. During the same period, 377 patients with K. pneumoniae bacteremia and 183 patients with Enterobacter bacteremia were identified and compared with those with P. aeruginosa bacteremia. RESULTS: Factors associated with P. aeruginosa bacteremia in the multivariate analysis included pneumonia, soft tissue infection, nosocomial acquisition, neutropenia, and prior invasive procedure (All P<0.05). The 30-day mortality rate was 37.9% (72/190) in patients with P. aeruginosa bacteremia, 24.1% (91/377) in those with K. pneumoniae, and 25.7% (47/183) in those with Enterobacter bacteremia (P<0.001). However, in the analysis including patients who had received appropriate initial antimicrobial therapy (n=552), the mortality rate of P. aeruginosa bacteremia was not significantly higher than that of non-pseudomonas bacteremia (28.6% [18/63] vs. 22.5% [110/489]; P=0.282). Inappropriate initial antimicrobial therapy was found to be one of the significant independent predictors of mortality. P. aeruginosa bacteremia as a risk factor for mortality did not reach statistical significance (OR, 1.30; 95% CI, 0.73-2.32; P=0.371), after adjusting for underlying illness and adequacy of antimicrobial therapy. CONCLUSION: An initial empirical antimicrobial coverage of P. aeruginosa should be seriously considered in patients with pneumonia, soft tissue infection, neutropenia, and prior invasive procedure, when gram-negative sepsis was suspected in nosocomial infection.
Bacteremia* ; Cross Infection ; Enterobacter* ; Gram-Negative Bacterial Infections ; Humans ; Klebsiella pneumoniae* ; Klebsiella* ; Mortality ; Multivariate Analysis ; Neutropenia ; Pneumonia ; Pseudomonas aeruginosa* ; Pseudomonas* ; Retrospective Studies ; Risk Factors ; Sepsis ; Soft Tissue Infections ; Treatment Outcome

BACKGROUND: This study was conducted to evaluate the risk factors for infection and clinical outcomes of bacteremic spontaneous bacterial peritonitis (SBP) due to ESBL-producing E. coli and K. pneumoniae, in patients with advanced liver cirrhosis. METHODS: The ESBL production was determined by NCCLS guidelines and/or double-disk synergy tests, on stored E. coli and K. pneumoniae blood isolates collected between 1998 and 2002. Of the patients with advanced liver cirrhosis, 15 case patients, with SBP due to ESBL-producers, were compared with 30 matched controls, with SBP due to non-ESBL-producers. RESULTS: There were no significant differences in age, sex, Child-Pugh scores, or APACHE II scores between the two groups. Significant factors associated with infection by ESBL-producing organisms, according to univariate analysis, were: ICU care, indwelling urinary catheter, central venous catheterization, an invasive procedure within the previous 72 hours, and prior use of antibiotics within the previous 30 days. When assessing the clinical response at 72 hours after the initial antimicrobial therapy, the treatment failure rate was significantly higher in the ESBL group (73.3% vs. 16.7%, p< 0.001). Also, overall 30-day mortality rates were 60% (9/15) in the ESBL groups and 23.3% (7/30) in the control group (p=0.015). CONCLUSION: Among patients with advanced liver cirrhosis, bacteremic SBP due to ESBL-producing E. coli and K. pneumoniae was associated with adverse outcomes, and significantly higher mortality.
Bacteremia/*complications/microbiology ; Case-Control Studies ; Escherichia coli Infections/*complications ; Female ; Humans ; Klebsiella Infections/*complications ; Korea ; Liver Cirrhosis/*complications ; Male ; Middle Aged ; Outcome Assessment (Health Care) ; Peritonitis/*microbiology

BACKGROUND: The therapeutic option is limited for the infections caused by organisms producing plasmid- mediated AmpC beta-lactamases, increasingly identified worldwide. Two sporadic patients with bacteremia caused by K. pneumoniae possessing an unusual inducible beta-lactam resistant phenotype were found in a university hospital. RESULTS:We conducted antibiotic susceptibility test according to NCCLS guideline. Also, we characterized beta-lactamase by isoelectric focusing. RESULTS: DHA-1 gene conferred the resistant phenotype. The patients had experienced treatment failure when treated with extended-spectrum cephalosporin. For the isolates the cephalosporin resistance was induced by clavulanic acid (and cefoxitin). CONCLUSION: Theses results suggest that the extended-spectrum cephalosporins might not provide optimal therapeutic option for inducible DHA-1-producing K. pneumoniae infection, even when the pathogens are susceptible in vitro.
Bacteremia ; beta-Lactamases* ; Cephalosporin Resistance ; Cephalosporins ; Clavulanic Acid* ; Humans ; Isoelectric Focusing ; Klebsiella pneumoniae* ; Klebsiella* ; Phenotype ; Pneumonia ; Treatment Failure

BACKGROUND: The therapeutic option is limited for the infections caused by organisms producing plasmid- mediated AmpC beta-lactamases, increasingly identified worldwide. Two sporadic patients with bacteremia caused by K. pneumoniae possessing an unusual inducible beta-lactam resistant phenotype were found in a university hospital. RESULTS:We conducted antibiotic susceptibility test according to NCCLS guideline. Also, we characterized beta-lactamase by isoelectric focusing. RESULTS: DHA-1 gene conferred the resistant phenotype. The patients had experienced treatment failure when treated with extended-spectrum cephalosporin. For the isolates the cephalosporin resistance was induced by clavulanic acid (and cefoxitin). CONCLUSION: Theses results suggest that the extended-spectrum cephalosporins might not provide optimal therapeutic option for inducible DHA-1-producing K. pneumoniae infection, even when the pathogens are susceptible in vitro.
Bacteremia ; beta-Lactamases* ; Cephalosporin Resistance ; Cephalosporins ; Clavulanic Acid* ; Humans ; Isoelectric Focusing ; Klebsiella pneumoniae* ; Klebsiella* ; Phenotype ; Pneumonia ; Treatment Failure