Osimertinib as first-line treatment for elderly patients with advanced EGFR mutation-positive non-small cell lung cancer in a real-world setting (OSI-FACT-EP).

OBJECTIVES: Osimertinib is the primary treatment for patients with epidermal growth factor receptor (EGFR) mutation-positive advanced non-small cell lung cancer. However, evidence of the outcomes of osimertinib treatment in patients over 75 years of age in the real-world setting is limited. MATERIALS AND METHODS: This retrospective study analyzed the data of 538 patients (203 elderly and 335 non-elderly) with EGFR mutation-positive lung cancer in whom osimertinib was initiated as first-line treatment between August 2018 and December 2019. Patients over 75 years of age were classified as elderly. The data cut-off date was February 28, 2022. RESULTS: The progression-free survival (PFS) did not significantly differ between the elderly and non-elderly groups [elderly group: median PFS, 16.9 months (95 % confidence interval (CI), 14.3-20.2); non-elderly group: median PFS, 22.1 months (95 % CI: 19.5-26.3); hazard ratio (HR) for the elderly against the non-elderly: 1.21 (95 % CI: 0.98-1.50), p = 0.079]. However, the time to treatment failure (TTF) was significantly shorter in the elderly than in the non-elderly [elderly group: median TTF, 14.0 months (95 % CI: 0.98-1.50); non-elderly group: median TTF, 21.8 months (95 % CI: 18.2-24.6); HR for the elderly against the non-elderly: 1.46 (95 % CI: 1.20-1.77), p < 0.001]. Furthermore, the rate of treatment discontinuation because of adverse events was 28.6 % in the elderly and 14.9 % in the non-elderly (p < 0.001). Among patients who discontinued treatment, the conversion rate to second-line treatment was 39.6 % in the elderly and 72.8 % in the non-elderly. In addition, the median overall survival was 30 months (95 % CI: 25.8-37.7) in the elderly and not reached (NR) (95 % CI: NR-NR) in the non-elderly (p < 0.001). CONCLUSION: In a real-world clinical setting, elderly patients receiving osimertinib as first-line treatment should be aware of the frequent inability to transition to second-line treatment due to adverse events.

Immunologic Significance of CD80/CD86 or Major Histocompatibility Complex-II Expression in Thymic Epithelial Tumors.

Introduction: Unresectable or recurrent thymic epithelial tumors (TETs) have a poor prognosis, and treatment options are limited. This study aimed to investigate the immunologic significance of CD80/CD86 or major histocompatibility complex class II (MHC-II) expression in TETs, as potential predictive biomarkers for immune checkpoint inhibitors (ICIs). Methods: We analyzed CD80, CD86, MHC class I (MHC-I), and MHC-II expression in TETs using immunohistochemistry and investigated their association with T-cell infiltration or ICI efficacy. In addition, we generated CD80- or MHC-II-expressing mouse tumors, evaluated the effects of ICIs, and analyzed tumor-infiltrating lymphocytes. We also performed tumor-rechallenge experiments in vivo. Results: We found that approximately 50% and 30% of TETs had high expression of CD80/CD86 and MHC-II in tumor cells, respectively, and that this expression was related to T-cell infiltration in clinical samples. In mouse models, both CD80 and MHC-II increase the effects of ICIs. In addition, senescent T cells and long-lived memory precursor effector T cells were significantly decreased and increased, respectively, in tumor-infiltrating lymphocytes from CD80-expressing tumors, and rechallenged tumors were completely rejected after the initial eradication of CD80-expressing tumors by programmed cell death protein 1 blockade. Indeed, patients with CD80-high thymic carcinoma had longer progression-free survival with anti-programmed cell death protein 1 monoclonal antibody. Conclusions: Half of the TETs had high expression of CD80/CD86 or MHC-II with high T-cell infiltration. These molecules could potentially increase the effects of ICIs, particularly inducing a durable response. CD80/CD86 and MHC-II can be predictive biomarkers of ICIs in TETs, promoting the development of drugs for such TETs.

Nationwide surveillance of bacterial respiratory pathogens conducted by the surveillance committee of the Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2019-2020: General view of the pathogens' antibacterial susceptibility.

The trends and prevalence of antimicrobial susceptibility of pathogens vary by country, region, and time. Long-term regular surveillance is required to investigate trends in the antimicrobial resistance of various isolated bacterial pathogens. We report the results of a nationwide surveillance on the antimicrobial susceptibility of bacterial respiratory pathogens in Japan conducted by the Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology. The isolates were collected from clinical specimens obtained from adult patients who visited a collaborating medical facility between June 2019 and December 2020 and were diagnosed with respiratory tract infections by a physician. Antimicrobial susceptibility testing was performed in a centralized laboratory according to the methods recommended by the Clinical and Laboratory Standards Institute. Susceptibility testing was performed for 932 strains (201 Staphylococcus aureus, 158 Streptococcus pneumoniae, 6 S. pyogenes, 136 Haemophilus influenzae, 127 Moraxella catarrhalis, 141 Klebsiella pneumoniae, and 163 Pseudomonas aeruginosa) collected from 32 facilities in Japan. The proportions of methicillin-resistant S. aureus and penicillin-resistant S. pneumoniae were 35.3% and 0%, respectively. In H. influenzae, 16.2% and 16.9% were ß-lactamase-producing ampicillin resistant and ß-lactamase-negative ampicillin resistant, respectively. Extended-spectrum ß-lactamase-producing K. pneumoniae accounted for 5.0% of all K. pneumoniae infections. Carbapenemase-producing K. pneumoniae and multi-drug-resistant P. aeruginosa with metallo-ß-lactamase were not detected in this study. This surveillance will be a useful reference for treating respiratory infections in Japan and will provide evidence to enhance the appropriate use of antimicrobial agents.

Venous Stent Placement for Malignant Vena Cava Syndrome in a Patient with Liposarcoma.

BACKGROUND Reports of venous stenting for inferior vena cava (IVC) syndrome (IVCS) due to sarcoma are limited, and the treatment's efficacy and safety are not clear. CASE REPORT A 36-year-old woman with myxoid liposarcoma was admitted to the Department of Respiratory Medicine for treatment of bilateral lower-leg edema and to be evaluated for acute liver dysfunction. She was 13 years old when she was diagnosed with myxoid liposarcoma. Over the next 18 years, she had 4 tumor resections and 1 round of radiation therapy. She had been on chemotherapy for 4 years and then pazopanib at the age of 35. The edema did not improve after admission despite treatment with diuretics. Computed tomography revealed a huge liposarcoma occupying the right thoracic cavity and a compressed IVC, which caused the edema. Although doxorubicin was administered as fifth-line treatment, there was no response. Since there was no additional chemotherapy regimen, her prognosis was considered to be less than 6 months. She could not be discharged to her home since she was unable to walk due to the edema; therefore, IVC stenting was performed to improve her dysmotility. After IVC stenting, the lower-leg edema improved without any adverse events, enabling her to walk and eventually return home. CONCLUSIONS In patients with IVCS caused by rare malignancies such as myxoid liposarcoma, an IVC stent can be safely implanted and can help to alleviate symptoms. IVC stenting can improve symptoms and allow for home care, resulting in improved quality of life.

Safety and efficacy of osimertinib rechallenge or continuation after pneumonitis: A multicentre retrospective cohort study.

INTRODUCTION: Although osimertinib is a standard first-line treatment for patients with advanced-stage non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations, the incidence rate of pneumonitis associated with osimertinib is high. However, there are few reports about the safety and efficacy of osimertinib rechallenge after the development of pneumonitis. METHODS: We conducted a retrospective multicentre cohort study of consecutive patients who developed pneumonitis associated with osimertinib as a first-line and received osimertinib rechallenge. The primary outcome was the incidence rate of any grade pneumonitis after osimertinib rechallenge. The secondary outcome was treatment efficacy in patients after osimertinib rechallenge. RESULTS: In total, 33 patients who received osimertinib rechallenge were included. Of them, 26 patients had grade 1, 6 patients had grade 2, and 1 patient had grade 3 initial pneumonitis. The median follow-up period after the osimertinib rechallenge was 16.9 months (interquartile range, 11.1-21.3 months). After the start of osimertinib rechallenge, five patients (15%) experienced mild relapsed pneumonitis. Three of the five patients had similar imaging patterns for initial and relapsed pneumonitis. No significant differences in characteristics were observed between patients with and without relapsed pneumonitis. The median progression-free survival after osimertinib rechallenge was not achieved (95% confidence interval: 10.3 months - not reached). CONCLUSION: Osimertinib rechallenge was feasible and effective for patients who developed initial pneumonitis associated with first-line osimertinib therapy. Osimertinib might be considered a treatment option even after the development of mild initial pneumonitis.

The Effect of Mild Renal Dysfunction on the Assessment of Plasma Amino Acid Concentration and Insulin Resistance in Patients with Type 2 Diabetes Mellitus.

Background: An increase in the levels of branched-chain amino acids (BCAAs) and certain aromatic amino acids, such as alanine, in plasma is correlated with insulin resistance (IR) in type 2 diabetes mellitus (T2DM). T2DM is a leading risk factor for chronic kidney disease. Meanwhile, renal dysfunction causes changes in plasma amino acid levels. To date, no study has examined how mild renal dysfunction and IR interact with plasma amino acid levels. This study examines the effects of IR and renal dysfunction on plasma amino acid concentrations in T2DM. Methods: Data were collected from healthy male participants (controls) and male patients with T2DM between May 2018 and February 2022. Blood samples were collected after overnight fasting. IR and renal function were evaluated using the homeostasis model assessment of IR (HOMA-IR) and serum cystatin C (CysC), respectively. Results: A total of 49 and 93 participants were included in the control and T2DM groups, respectively. In the T2DM group, eight amino acids (alanine, glutamic acid, glutamine, glycine, isoleucine, leucine, tyrosine, and valine) and total BCAA showed a significant correlation with HOMA-IR (p < 0.01), whereas six amino acids (γ-aminobutyric acid, citrulline, cysteine, glycine, methionine, and valine) and total BCAA showed a significant correlation with 1/CysC (p < 0.02). However, only alanine, glutamic acid, and each BCAA showed significant differences between the control group and the IR T2DM subgroup. Increases in the BCAA levels with T2DM were canceled by renal dysfunction (CysC ≥ 0.93) in patients with intermediate IR. Conclusion: To use plasma BCAA concentration as a marker of IR, renal function must be considered, even in mild renal dysfunction. Increased alanine and glutamic acid levels indicate IR, regardless of mild renal dysfunction.

Changes in plasma-concentration ratios of branched-chain amino acids in acute and convalescent phases of bacterial pneumonia.

Branched-chain amino acids (BCAAs) have different immunity-related functions. Thus, BCAAs require evaluation in terms of their plasma concentration ratio. Eighty healthy participants and 57 patients with community-acquired pneumonia were enrolled. Samples from the healthy participants were collected after 12-h fasting; samples from the community-acquired pneumonia group were collected 2-3 h after lunch, during the acute (day 0) and convalescent (day 7) phases. The coefficient "a" of the regression line (Y = aX + b) of each BCAA plasma concentration was calculated from healthy participants and fixed, and each intercept "b" was calculated from the plasma concentration of each BCAA pair. Isoleucine levels increased; no significant changes in leucine concentrations were observed between healthy participants and pneumonia patients on days 0 and 7. In female participants in the pneumonia group, valine concentrations decreased on day 0. The isoleucine concentration was relatively higher than the leucine concentration on day 7 when evaluated with "b". Changes in "b" on days 0 and 7 differed between men and women. There were sex-related differences in the plasma concentration ratios of BCAAs evaluated by "b", which indicates a possible sex-related difference in the metabolic response to bacterial infection.

Drug-Related Pneumonitis Induced by Osimertinib as First-Line Treatment for Epidermal Growth Factor Receptor Mutation-Positive Non-Small Cell Lung Cancer: A Real-World Setting.

BACKGROUND: Osimertinib has demonstrated impressive efficacy as a first-line treatment for patients with advanced epidermal growth factor receptor (EGFR) mutation-positive (m+) lung cancer. Drug-related pneumonitis (DRP) is a potentially lethal complication of osimertinib treatment, but reliable real-world data currently are lacking. RESEARCH QUESTION: What is the prevalence of osimertinib-induced DRP in first-line settings? What are the characteristics, clinical impact, and risk factors of osimertinib-induced DRP? STUDY DESIGN AND METHODS: We conducted a retrospective multicenter cohort study of patients who received osimertinib as a first-line treatment for advanced EGFR m+ non-small cell lung cancer (NSCLC) between August 2018 and December 2019. All chest CT scans and clinical information during osimertinib exposure were collected until June 2020. The primary end point was DRP incidence identified through central review. RESULTS: A total of 452 patients from 18 institutions were evaluated. Eighty patients (18%) had a diagnosis of DRP (all grades), and 21 patients (4.6%) had a diagnosis of grade 3 or more DRP. Among the patients with DRP, 46% were identified as having transient asymptomatic pulmonary opacity (TAPO). Regarding the CT scan patterns, organizing pneumonia, simple pulmonary eosinophilia, hypersensitivity pneumonia, diffuse alveolar damage, and nonspecific interstitial pneumonia were found in 30, 21, 18, 9, and two patients (38%, 26%, 23%, 11%, and 3%), respectively. In multivariate analysis, smoking history was identified as an independent risk factor for DRP (hazard ratio, 1.72; 95% CI, 1.01-2.89; P = .046). In the 3-month landmark analysis, DRP was associated with poor treatment efficacy; however, the presence of TAPO did not affect treatment efficacy negatively. INTERPRETATION: For osimertinib treatment in first-line settings, the frequency of DRP was considerably elevated to 18 %, and half of these patients exhibited TAPO features.

Histologic transformation of epidermal growth factor receptor-mutated lung cancer.

PURPOSE: This study aimed to determine the incidence and clinical course of epidermal growth factor receptor (EGFR)-mutated lung cancer with histologic transformation (HT). PATIENTS AND METHODS: We conducted a multicentre, retrospective, cohort study of patients with advanced EGFR-mutated lung cancer who received EGFR-tyrosine kinase inhibitors (TKIs) between 2012 and 2019. The primary outcome was the incidence of HT. The secondary outcome was treatment efficacy in patients with HT. RESULTS: In total, 6356 patients were enrolled. In 2624 patients, the histological type was proven by rebiopsy after acquiring resistance to EGFR-TKIs. Among them, 74 patients had HT (incidence rate: 2.8% [95% confidence interval: 2.3%-3.5%]). The median progression-free survival after EGFR-TKIs and first-line therapy after confirming HT was 10.4 and 4.4 months, respectively, which was not significantly different between patients with transformation to high-grade neuroendocrine carcinoma and those with transformation to another subtype of non-small cell lung cancer. Overall survival after confirming HT was 12.2 months. Twenty-seven patients received immune checkpoint inhibitors: 6 and 21 received immune checkpoint inhibitors before and after confirming HT, respectively. No patients achieved 1-year progression-free survival. The median progression-free survival after immune checkpoint inhibitor therapy after confirming HT was 1.6 months. CONCLUSION: HT occurred in approximately 3% of EGFR-mutated patients who developed resistance to EGFR-TKIs. Cytotoxic agents are likely to be effective in patients with HT. However, the therapeutic effectiveness of immune checkpoint inhibitors was limited in these patients. Given the rarity of HT and absence of prospective trials, our findings are important to inform the treatment of these patients.

Aging, cancer, and antitumor immunity.

Aging leads to numerous changes that affect many components of the immune system, called "immunosenescence". Indeed, elderly individuals exhibit dysregulated immune responses against pathogens, poor responses to vaccination, and increased susceptibility to many diseases including cancer, autoimmune disorders, and other chronic inflammatory diseases. Despite progressed understanding of immunosenescence, its detailed mechanisms are still not fully understood. With advances in medicine, the population of older cancer patients is expected to rapidly increase in the coming years. Cancer immunotherapies, including immune checkpoint inhibitors (ICIs), have been shown to be effective for multiple cancer types, whereas to date, few specific data for elderly individuals have been published. Some systemic reviews have demonstrated that ICIs exhibit similar efficacy in older cancer patients, but they seem to be less effective in very old patients. In addition, toxicities might be more frequently observed in such patients. Here, we provide a summary to better understand immunosenescence and an overview of its relationship with cancer and antitumor immunity, including the efficacy and toxicity of ICIs.

Osimertinib as first-line treatment for advanced epidermal growth factor receptor mutation-positive non-small-cell lung cancer in a real-world setting (OSI-FACT).

BACKGROUND: Osimertinib is the standard of care in the initial treatment for advanced epidermal growth factor receptor (EGFR) mutation-positive lung cancer. However, clinical data and reliable prognostic biomarkers are insufficient. METHODS: We performed a retrospective multicentre cohort study for 538 EGFR mutation-positive patients, who received osimertinib as the initial treatment between August 2018 and December 2019. The main outcome was progression-free survival (PFS). RESULTS: The median observation period was 14.7 months (interquartile range 11.4-20.0). The median PFS was 20.5 months (95% confidence interval [CI] 18.6-not reached). Multivariate analysis showed that sex (male) (hazard ratio [HR] 1.99, 95% CI 1.35-2.93, P = 0.001), malignant effusions (HR 1.51, 95% CI 1.11-2.04, P = 0.008), liver metastasis (HR 1.55, 95% CI 1.03-2.33, P = 0.037), advanced unresectable cases (HR 1.71, 95% CI, 1.04-2.82, P = 0.036), mutation type and programmed cell death-ligand 1 (PD-L1) expression were associated with PFS. The L858R (HR 1.55, 95% CI 1.01-2.38, P = 0.043) and uncommon mutations (HR 3.15, 95% CI 1.70-5.83, P < 0.001) were associated with PFS. PD-L1 expression of 1-49% (HR 1.66, 95% CI 1.05-2.63, P = 0.029), ≥50% (HR 2.24, 95% CI 1.17-4.30, P = 0.015) and unknown (HR 1.53, 95% CI 1.05-2.22, P = 0.026) was associated with PFS. The main reasons for treatment discontinuation among 219 patients were disease progression (44.3%), pneumonitis (25.5%) and other adverse events (16.0%). CONCLUSION: During initial treatment with osimertinib, PD-L1 expression is significantly related to PFS. Adverse events are a noteworthy reason for discontinuation.

Plasma amino acid levels in individuals with bacterial pneumonia and healthy controls.

BACKGROUND & AIMS: Amino acids play an important role in immune responses and as neurotransmitters. During the course of a bacterial pneumonia episode, from the onset to the recovery phase, immune responses dramatically change, as does the metabolism of amino acids, a concept referred to as immuno-nutrition. We investigated the differences in plasma amino acid levels (PAA) between the acute and recovery phases in individuals with community-acquired pneumonia (CAP) and healthy controls. METHODS: Two groups of participants were recruited: Healthy adults aged over 60 years and patients hospitalized with CAP. Samples were collected on Day 0 (the day of admission) and Day 7 (after 6-8 days treatment). RESULTS: A total of 93 healthy adults and 60 patients with CAP participated in the study. Of those with CAP, 43 had their amino acids measured on Day 7. Patients with CAP had markedly decreased PAA of 12 amino acids on Day 0. Citrulline, histidine, and tryptophan remained low in male, while aspartic acid, asparagine, ornithine, proline, and threonine were higher on Day 7 in both males and females. Phenylalanine increased at Day 0 and Day7. CONCLUSIONS: The findings suggest that the host response against bacterial infection changed the plasma amino acid levels. PAA on Day 7 (representing convalescence) continued to display an amino acid profile distinct from that observed in healthy individuals. Based on these findings, reconsideration for providing amino acids to patients with bacterial pneumonia should be needed depending on stage of the pneumonia from the perspective of immuno-nutrition.

Voriconazole treatment of pulmonary mycosis caused by Chrysosporium zonatum after treatment for pulmonary tuberculosis.

Chrysosporium zonatum is a soil-dwelling fungus that rarely causes pulmonary infections, and a small number of cases have been reported to date. A 74-year-old man, who had previously been treated for tuberculosis, presented with symptoms of low-grade fever, anorexia, cough, and bloody sputum. Chest computed tomography (CT) showed a thick-walled cavitary lesion in the right upper lobe, in which there was a suspected mycotic mass. Initially, the patient was suspected to have chronic aspergillosis due to positive serum anti-Aspergillus antibodies. However, bronchoscopic culture revealed the growth of C. zonatum. Symptoms and imaging findings improved with administration of voriconazole for 18 months. Infection by C. zonatum is very rare and is difficult to differentiate from aspergillosis by clinical features. Clinicians should be aware of the possibility of coinfection with C. zonatum and Aspergillus sp. Voriconazole may be an effective treatment option.

Short-Term Corticosteroid Therapy for Early Exacerbation of COVID-19 Pneumonia: A Case Report.

BACKGROUND The effect of corticosteroids in the management of patients with coronavirus disease 2019 (COVID-19) is unclear. CASE REPORT A 67-year-old man who tested positive for COVID-19 by reverse-transcription PCR (RT-PCR) analysis was admitted to our hospital. On admission, he had no dyspnea and his oxygen saturation (SpO2) level was normal. Chest imaging revealed ground-glass opacities (GGO) distributed in both lung fields. Four days after admission, bilateral lung shadows worsened, with a slight reduction in SpO2 levels. Short-term corticosteroid therapy was initiated, and SpO2 and radiographic findings promptly improved without use of antiviral agents. CONCLUSIONS More data are required to ascertain the role of corticosteroids in the management of COVID-19 pneumonia.

Cross-correlation of plasma concentrations of branched-chain amino acids: A comparison between healthy participants and patients with chronic kidney disease.

BACKGROUND & AIMS: Plasma concentrations of branched-chain amino acids (BCAAs) are known to exhibit strong intercorrelations; however, the associated regulatory mechanism is not sufficiently understood. Furthermore, the mechanisms underlying the intercorrelation changes in metabolic disorders with the disease are unclear. Therefore, plasma BCAAs in patients with chronic kidney disease (CKD) were examined. METHODS: This study included a healthy group of older participants (Group C; n = 87, 46 males, 41 females) who had undergone health examinations at Sanyudo Hospital and a group of CKD patients (Group CKD; n = 71, 49 males, 22 females) receiving maintenance hemodialysis at the same hospital. Samples from Group C were collected 12 h after fasting. CKD samples were collected before and after hemodialysis (pre-HD and post-HD, respectively), without 12 h fasting. The samples were analyzed for 38 amino acids by SRL Inc., using liquid chromatography-mass spectrometry (LC-MS). RESULTS: Differences between the plasma BCAA concentrations of Group C and pre-HD were determined. Dialysis-induced BCAA losses were different for each BCAA. However, strong intercorrelations between the plasma concentrations of each BCAA were maintained. In addition, the regression lines did not converge at the origin and were in different positions for groups C, pre-HD, and post-HD. A different distribution of the constant (b) for each group was observed for each BCAA correlation when a in the regression line (Y = aX + b) was fixed at the value for Group C, and b was calculated. CONCLUSION: Strong intercorrelations among plasma concentrations of BCAAs were maintained in CKD patients both pre- and post-dialysis, whereas the changes in the plasma concentrations of each BCAA were different. We speculate that there is a novel mechanism that selectively regulates each BCAA and suggest that changes in the constant of the regression formula for correlation may have a novel function as an index for renal contribution to BCAA metabolism.

Nationwide surveillance of bacterial respiratory pathogens conducted by the surveillance committee of japanese society of chemotherapy, the japanese association for infectious diseases, and the japanese society for clinical microbiology in 2016: General view of the pathogens' antibacterial susceptibility.

The nationwide surveillance on antimicrobial susceptibility of bacterial respiratory pathogens from the patients in Japan was conducted by the Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2016. The isolates were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections during the period between February 2016 and August 2016 by three societies. Antimicrobial susceptibility testing was conducted at the central reference laboratory according to the method recommended by Clinical Laboratory Standards Institute. Susceptibility testing was evaluated in 1062 strains (143 Staphylococcus aureus, 210 Streptococcus pneumoniae, 17 Streptococcus pyogenes, 248 Haemophilus influenzae, 151 Moraxella catarrhalis, 134 Klebsiella pneumoniae, and 159 Pseudomonas aeruginosa). Ratio of methicillin-resistant S. aureus was 48.3%, and those of penicillin-susceptible S. pneumoniae was 99.5%. Among H. influenzae, 14.1% of them were found to be ß-lactamase-producing ampicillin-resistant strains, and 41.1% to be ß-lactamase-non-producing ampicillin-resistant strains. Extended spectrum ß-lactamase-producing K. pneumoniae and multi-drug resistant P. aeruginosa with metallo ß-lactamase were 4.5% and 0.6%, respectively.

Pulmonary Cryptococcosis in a Nurse Initially Suspected of Having Pulmonary Tuberculosis.

BACKGROUND Pulmonary cryptococcosis can be associated with various imaging findings and can occur in immunocompetent hosts. It is sometimes difficult to distinguish pulmonary cryptococcosis from pulmonary tuberculosis based on imaging findings. CASE REPORT A 34-year-old female nurse who worked in an endoscopy examination room visited our hospital because of an abnormal lung shadow. At her workplace, a gastrointestinal endoscopy had been performed on a patient with infectious tuberculosis. The nurse was asymptomatic, and acid-fast staining and culture of her sputum were negative. Chest computed tomography depicted multiple nodules distributed along the bronchi. An acid-fast smear test of bronchial lavage was negative and cytological investigations revealed many yeast-like fungi. Fluconazole was administered and the computed tomography findings improved. CONCLUSIONS It is important to consider cryptococcosis, even in patients suspected of having tuberculosis.

Differences in plasma amino acid levels in patients with and without bacterial infection during the early stage of acute exacerbation of COPD.

PURPOSE: No consensus has been reached regarding appropriate nutritional intervention and rehabilitation during early acute exacerbation of COPD (AECOPD). Given the individual differences in symptoms of AECOPD, patients should be classified by their pathology. For example, it is known that there are differences in the inflammatory response between AECOPD with and without bacterial infection. However, there have been few reports on AECOPD from a nutritional perspective. The aim of this study was to investigate amino acid levels in patients with AECOPD. PATIENTS AND METHODS: Blood was collected from patients who were hospitalized with AECOPD and from patients with COPD that was in a stable state. We divided the patients with AECOPD into those without bacterial infection (group A) and those with bacterial infection (group B). The patients with COPD that was stable served as controls (group C). The plasma levels of 9 essential amino acids, 13 nonessential amino acids, and total amino acids were compared between the three groups. RESULTS: In the early stages of AECOPD, differences in plasma levels of only three amino acids (glycine, phenylalanine, and arginine) were observed between groups C and A. Differences in total amino acids and 13 amino acids were observed between groups C and B. Group B had lower levels of total amino acids and of seven amino acids (asparagine, citrulline, glutamine, histidine, methionine, serine, and threonine) compared with the other study groups. CONCLUSION: The findings of this study show that amino acid levels in plasma differ in patients with AECOPD depending on whether or not bacterial infection is present. Our results suggest that specific amino acids (ie, asparagine, citrulline, glutamine, histidine, serine, and threonine) have potential utility as diagnostic markers to distinguish between bacterial and nonbacterial AECOPD.

Characteristics and Prognosis of Patients with Immunoglobulin M Monoclonal Gammopathy.

Many patients with immunoglobulin M (IgM) monoclonal gammopathy remain asymptomatic and, consequently, untreated; however, few studies have evaluated the clinical course and prognosis of these patients. Using the screening procedures at our hospital, 74 patients with IgM monoclonal gammopathy were selected. We excluded 11 patients in whom the treatment for lymphoid neoplasms had been initiated at the time of IgM monoclonal protein detection. The remaining 63 patients were considered to be the patient population with IgM MGUS and asymptomatic WM, and were analyzed. In these patients, the median overall survival was longer than 14 years. More than half of these patients died from causes other than lymphoid neoplasm. The cumulative incidence of lymphoid neoplasm requiring treatment was 17.5%. In five of eight patients requiring treatment for lymphoid neoplasms, the causes of death were related with these lymphoid neoplasms. Our study suggests that not all patients with IgM monoclonal gammopathy require uniform treatment for prolonged survival; however, most lymphoid neoplasms requiring treatment are refractory diseases. Our findings may help manage patients with macroglobulinemia.