Infectious virus shedding duration reflects secretory IgA antibody response latency after SARS-CoV-2 infection.

Infectious virus shedding from individuals infected with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is used to estimate human-to-human transmission risk. Control of SARS-CoV-2 transmission requires identifying the immune correlates that protect infectious virus shedding. Mucosal immunity prevents infection by SARS-CoV-2, which replicates in the respiratory epithelium and spreads rapidly to other hosts. However, whether mucosal immunity prevents the shedding of the infectious virus in SARS-CoV-2-infected individuals is unknown. We examined the relationship between viral RNA shedding dynamics, duration of infectious virus shedding, and mucosal antibody responses during SARS-CoV-2 infection. Anti-spike secretory IgA antibodies (S-IgA) reduced viral RNA load and infectivity more than anti-spike IgG/IgA antibodies in infected nasopharyngeal samples. Compared with the IgG/IgA response, the anti-spike S-IgA post-infection responses affected the viral RNA shedding dynamics and predicted the duration of infectious virus shedding regardless of the immune history. These findings highlight the importance of anti-spike S-IgA responses in individuals infected with SARS-CoV-2 for preventing infectious virus shedding and SARS-CoV-2 transmission. Developing medical countermeasures to shorten S-IgA response time may help control human-to-human transmission of SARS-CoV-2 infection and prevent future respiratory virus pandemics.

Difference in the impact of coinfections and secondary infections on antibiotic use in patients hospitalized with COVID-19 between the Omicron-dominant period and the pre-Omicron period.

INTRODUCTION: This study evaluated the effect of coinfections and/or secondary infections on antibiotic use in patients hospitalized with coronavirus disease 2019 (COVID-19). METHOD: Days of therapy per 100 bed days (DOT) in a COVID-19 ward were compared between 2022 (Omicron period) and 2021 (pre-Omicron period). Antibiotics were categorized as antibiotics predominantly used for community-acquired infections (CAIs) and antibiotics predominantly used for health care-associated infections (HAIs). Bacterial and/or fungal infections which were proved or assumed on admission were defined as coinfections. Secondary infections were defined as infections that occurred following COVID-19. RESULTS: Patients with COVID-19 during the Omicron period were older and had more comorbidities. Coinfections were more common in the Omicron period than in the pre-Omicron period (44.4% [100/225] versus 0.8% [2/257], respectively, p < 0.001), and the mean DOT of antibiotics for CAIs was significantly increased in the Omicron period (from 3.60 to 17.84, p < 0.001). Secondary infection rate tended to be higher in the Omicron period (p = 0.097). Mean DOT of antibiotics for HAIs were appeared to be lower in the COVID-19 ward than in the general ward (pre-Omicron, 3.33 versus 6.37, respectively; Omicron, 3.84 versus 5.22, respectively). No multidrug-resistant gram-negative organisms were isolated in the COVID-19 ward. CONCLUSION: Antibiotic use for CAIs was limited in the pre-Omicron period but increased in the Omicron period because of a high coinfection rate on admission. With the antimicrobial stewardship, excessive use of antibiotics for HAIs was avoided in the COVID-19 ward during both periods.

Influence of easing COVID-19 strategies following downgrading of the national infectious disease category on COVID-19 occurrence among hospitalized patients in Japan.

PURPOSE: We aimed to evaluate the influence of easing COVID-19 preventive measures following its downgrading to a common infectious disease on COVID-19 occurrence among hospitalized patients. METHODS: Nosocomial occurrence of COVID-19 was compared between periods with national infectious disease category 5 versus the preceding category 2 equivalent. Changes in the revised manual included a shorter duration of work restrictions for infected health care practitioners (HCPs); no work restriction for HCPs exposed to SARS-CoV-2 with a negative test on days 1, 3 and 5; discontinuation of universal pre-admission screening; and pre-emptive isolation of patients without screening. Wearing an N95 mask and face shield was required in procedure/care with moderate-to high-risk contact. RESULTS: Although the mean monthly number of infected HCPs increased from 8.1 to 12.7 in the category 5 period (p = 0.034) and that of pre-admission screening decreased to one-fourth, the COVID-19 incidence in hospitalized patients remained similar between the two study periods (1.60 ± 5.59/month versus 1.40 ± 2.63/month, p = 0.358). Clusters, defined as ≥3 COVID-19 patients on the ward, were experienced twice in the preceding period and only once in the category 5 period. The index cases causing nosocomial SARS-CoV-2 transmission mostly involved rehabilitation therapists in the preceding period; five of six index cases were patients in the category 5 period. Following the expanded indication for N95 masks, neither SARS-CoV-2 transmission to patients nor transmission from infected patients was observed in HCPs for 1 year. CONCLUSION: With sustained, enhanced standard precautions, easing prevention strategies could limit nosocomial SARS-CoV-2 infections.

Clinical features of pasteurellosis without an animal bite or scratch in comparison with bite/scratch pasteurellosis.

Pasteurellosis is a common zoonotic infection that occurs after an animal bite or scratch (B/S). We compared the clinical features of six patients with non-B/S pasteurellosis with those of 14 patients with B/S infections. Pasteurella multocida was identified with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry in all six non-B/S infections, whereas 13 of the 14 B/S infections were identified with diagnostic kits. The non-B/S infections were pneumonia (n = 3), skin and soft tissue infections (n = 2), and bacteremia (n = 1). Pneumonia occurred in two patients with underlying pulmonary disease, whereas ventilator-associated pneumonia developed in one patient with cerebral infarction. Pasteurella multocida was isolated from a blood specimen and nasal swab from a patient with liver cirrhosis (Child-Pugh class C) and diabetes. Cellulitis developed in one patient with diabetes and normal-pressure hydrocephalus, who had an open wound following a fall, and in one patient with diabetes and a foot ulcer. Three patients with non-B/S infections had no pet and no episode of recent animal contact. The rate of moderate-to-severe comorbidities was significantly higher in patients with non-B/S infections than in those with B/S infections (100% and 14.3%, respectively, p < 0.001). In conclusion, non-B/S infections can develop in patients with chronic pulmonary disease, invasive mechanical ventilation, or open wounds, or who are immunocompromised, irrespective of obvious animal exposure. In contrast to B/S infections, non-B/S pasteurellosis should be considered opportunistic.

Surgical antimicrobial prophylaxis in Japanese hospitals: Real status and challenges.

BACKGROUND: Information regarding the status of surgical antimicrobial prophylaxis (SAP) in Japanese hospitals is lacking. This study aimed to explore the status of SAP prescriptions for surgeries and adherence to Japanese SAP guidelines. METHODS: From February to July 2020, a 1-day multicentre point prevalent survey was conducted at 27 hospitals in Aichi Prefecture, Japan. Patients prescribed SAP were included in this study. The appropriateness of the SAP was evaluated based on the guidelines for selection of antimicrobials and their duration. Surgery was defined as appropriate when all the items were appropriate. RESULTS: A total of 728 patients (7.1 %; 728/10,199) received antimicrobials for SAP. Among them, 557 patients (76.5 %, 557/728) underwent the surgeries described in the guidelines. The overall appropriateness of all surgeries was 33.9 % (189/557). The appropriate selection of antimicrobial before/during and after surgery and their durations were 67.5 % (376/557), 67.5 % (376/557), and 43.3 % (241/557), respectively. The overall appropriateness ranged from 0 % (0/37, oral and maxillofacial surgery) to 58.7 % (88/150, orthopaedic surgery) and 27.7 % (36/130, community hospitals with 400-599 beds) to 47.2 % (17/36, specific hospitals). Cefazolin was the most prevalent antimicrobial prescribed before/during (55.5 %, 299/539), and after (45.1 %, 249/552) surgery. In total, 101 oral antimicrobials were prescribed postoperatively. CONCLUSIONS: SAP adherence by specific surgical fields and hospitals was shown in this study. Intensive intervention and repeated surveillance are necessary to improve SAP prescriptions in Japanese hospitals.

Association between the hypokalaemia index based on area over the serum potassium concentration curve and occurrence of acute kidney injury in patients administered liposomal amphotericin B.

BACKGROUND: Acute kidney injury (AKI) and hypokalaemia are common adverse events after treatment with liposomal amphotericin B (L-AMB). OBJECTIVES: Because excess potassium (K) leakage occurs during renal tubular injury caused by L-AMB, measuring the decrease in rate of serum K concentration might be more useful to assess the renal impact of L-AMB than hypokalaemia identified from a one-point measurement. The effects of a decrease in K concentration and duration of hypokalaemia on AKI were investigated. METHODS: A ≥ 10% decrease in K concentration from the reference concentration within a 7-day timeframe was evaluated. The hypokalaemia index, which combines the duration of K concentration lower than the reference and a marked low K concentration, was calculated from the area over the concentration curve. RESULTS: Eighty-six patients were included in the study. The incidences of AKI and decrease in K concentration were 36.0% and 63.9%, respectively. Of patients who developed both adverse events, a decrease in K concentration occurred first in 22 of 26 patients, followed by AKI 7 days later. Hypokalaemia did not increase AKI risk whereas a decrease in K concentration was an independent risk factor for AKI. The hypokalaemia index in patients with AKI was significantly higher than those without AKI (5.35 vs. 2.50 points, p = 0.002), and ≥3.45 points was a significant predictor for AKI. CONCLUSION: A ≥ 10% decrease in the K concentration was a significant factor for AKI in patients receiving L-AMB therapy. In such patients, dose reduction or alternative antifungals could be considered based on the hypokalaemia index.

Judicious ending of isolation based on reverse transcription-polymerase chain reaction (RT-PCR) cycle threshold only for patients with coronavirus disease 2019 (COVID-19) requiring in-hospital therapy for longer than 20 days after symptom onset.

BACKGROUND: For patients with coronavirus disease 2019 (COVID-19) requiring hospitalization, extending isolation is warranted. As a cautious protocol, ending isolation based on polymerase chain reaction cycle threshold (Ct) value was introduced for patients requiring therapy for >20 days after symptom onset. METHOD: We compared a Ct-based strategy using Smart Gene® between March 2022 and January 2023 with a preceding control period (March 2021 to February 2022) when two consecutive negative reverse transcription-polymerase chain reaction tests using FilmArray® were required for ending isolation. Ct was evaluated on day 21, and ending isolation was permitted in patients with Ct ≥ 38. Although patients with Ct 35-37 were transferred to a non-COVID-19 ward, isolation was continued. RESULTS: The duration of stay on a COVID-19 ward in the Ct group was 9.7 days shorter than that in controls. The cumulative number of tests was 3.7 in controls and 1.2 in the Ct group. There was no nosocomial transmission after ending isolation in either group. The number of days from symptom onset to testing was 20.7 ± 2.1 in Ct group, and five patients had Ct < 35, nine Ct 35-37, and 71 Ct ≥ 38. No patients were moderately or severely immunocompromised. Steroid use was an independent risk factor for prolonged low Ct (odds ratio 9.40, 95% confidence interval 2.31-38.15, p = 0.002) CONCLUSIONS: The efficacy of ending isolation based on Ct values could improve bed utilization without the risk of transmission among patients with COVID-19 requiring therapy for >20 days after symptom onset.

Changes in self-efficacy associated with success in quitting smoking in participants in Japanese smoking cessation therapy.

AIMS: To identify the strength of self-efficacy during 12-week smoking cessation therapy (SCT) that consisted of 5 sessions and its association with the success of smoking cessation at the end of SCT. BACKGROUND: Few studies showed to what level self-efficacy should be reinforced to facilitate success in smoking cessation. DESIGN: Prospective cohort study. METHODS: We enrolled 488 smokers who received SCT from 6 Japanese smoking cessation clinics between October 2008 and October 2014. In each smoker, the self-efficacy of quitting smoking was assessed at each session of SCT. The association of the strength of self-efficacy with the success of smoking cessation was investigated by logistic regression analysis adjusting for age, gender, having a present illness, prescription, and nicotine dependence score. RESULTS: The self-efficacy of the 398 abstainers was significantly higher than that of the 90 nonabstainers at the first to fifth sessions of the SCT (P < .001 each). Participants with self-efficacy scores of greater than 60% were significantly more likely to attain abstinence than those with scores of 40% and less. CONCLUSION: During SCT, nurses' counselling to maintain patients' self-efficacy scores of smoking cessation in the range from 61% to 100% may be important for assisting patients in achieving smoking cessation.

Cognitive, behavioural and psychosocial factors associated with successful and maintained quit smoking status among patients who received smoking cessation intervention with nurses' counselling.

AIM: To identify cognitive, behavioural and psychosocial factors associated with successful and maintained quit smoking status after patients received smoking cessation intervention with nurses' counselling. BACKGROUND: Although nurses' intervention for smoking cessation is effective for patients, few studies have been conducted to identify cognitive, behavioural and psychosocial factors associated with the success of quitting smoking. DESIGN: Prospective cohort study METHODS: In a multi-institutional study between October 2008 - October 2014, we administered the Japanese smoking cessation therapy, which consists of smoking cessation intervention five times with nurses' counselling over 12 weeks. Log-binomial regression analysis was performed in 1,320 participants using the following independent variables: age, gender, having a present illness, prescription, Fagerström test for nicotine dependence, strength of desire to quit, age at smoking initiation, previous abstinence, motivation of quit smoking, self-efficacy of quit smoking and Center for Epidemiologic Studies Depression Scale. Factors associated with maintained cessation for 12 months were identified in the 541 abstainers at the end of the intervention. RESULTS: Having higher self-efficacy to quit smoking as assessed before the intervention was significantly associated with the success of quitting smoking at the end of the intervention. Strong desire to smoke as assessed at the end of the intervention was associated with significantly increased risk of discontinuing cessation during the 12 months after the end of the intervention. CONCLUSION: It is important for nurses who provide smoking cessation intervention to reinforce patients' self-efficacy and to control the strength of the patients' desire to smoke by behavioural counselling.

Varenicline is more effective in attenuating weight gain than nicotine patch 12 months after the end of smoking cessation therapy: an observational study in Japan.

INTRODUCTION: Although both varenicline and nicotine patch have a beneficial effect in controlling postcessation weight gain, it is not well known whether there is a difference in the effect. METHODS: We conducted a multi-institutional study on smoking cessation therapy (SCT) administered at 4 Japanese hospitals to compare the body weight change from the first session to 12 months after the end of SCT (at 60 weeks) between varenicline users (n = 307) and nicotine patch users (n = 45). RESULTS: The mean weight change from baseline to 12 months after the end of SCT was +0.94 kg (SD: 3.59) in varenicline users and +2.78 kg (SD: 4.88) in nicotine patch users (p = .003, by t test). In multivariate linear regression analysis, varenicline users gained significantly less weight than nicotine patch users (coefficient: -1.787, 95% CI = -2.98 to -0.59) with adjustment for success of quit smoking, age, sex, presence of comorbidity, body mass index at baseline, Fagerström Test for Nicotine Dependence, craving at the end of SCT, and nausea through the SCT. CONCLUSION: Our results indicated that varenicline is more effective in attenuating weight gain than nicotine patch in smokers who received Japanese SCT.

Healthcare-associated infections in Japanese hospitals: results from a large-scale multicenter point-prevalence survey in Aichi, 2020.

OBJECTIVE: Healthcare-associated infections (HAIs) pose significant challenges to healthcare systems worldwide. Epidemiological data are essential for effective HAI control; however, comprehensive information on HAIs in Japanese hospitals is limited. This study aimed to provide an overview of HAIs in Japanese hospitals. METHODS: A multicenter point-prevalence survey (PPS) was conducted in 27 hospitals across the Aichi Prefecture between February and July 2020. This study encompassed diverse hospital types, including community, university, and specialized hospitals. Information on the demographic data of the patients, underlying conditions, devices, HAIs, and causative organisms was collected. RESULTS: A total of 10,199 patients (male: 5,460) were included in this study. The median age of the patients was 73 (interquartile range [IQR]: 56-82) years, and the median length of hospital stay was 10 (IQR: 4-22) days. HAIs were present in 6.6% of patients, with pneumonia (1.83%), urinary tract infection (1.09%), and surgical site infection (SSI) (0.87%) being the most common. The prevalence of device-associated HAIs was 0.91%. Staphylococcus aureus (17.3%), Escherichia coli (17.1%), and Klebsiella pneumoniae (7.2%) were the primary pathogens in 433 organisms; 29.6% of the Enterobacterales identified showed resistance to third-generation cephalosporins. Pneumonia was the most prevalent HAI in small-to-large hospitals (1.69%-2.34%) and SSI, in extra-large hospitals (over 800 beds, 1.37%). CONCLUSIONS: This study offers vital insights into the epidemiology of HAIs in hospitals in Japan. These findings underscore the need for national-level PPSs to capture broader epidemiological trends, particularly regarding healthcare challenges post-COVID-19.

Factors associated with weight gain after smoking cessation therapy in Japan.

BACKGROUND: Smoking cessation is often followed by weight gain, which may attenuate motivation to sustain a quit attempt. OBJECTIVES: The aim was to identify factors associated with weight gain in smokers who received smoking cessation therapy (SCT) in Japan. METHODS: The weight change in 283 smokers between baseline and 12 months after finishing SCT was observed. Factors associated with marked weight gain of 3.5 kg or more were identified using stepwise logistic regression. RESULTS: Smoking cessation success was 83% (234/283) at the completion of SCT but decreased to 69% (194/283) 12 months later. Twelve months after the end of SCT, age 50 and over (OR = 0.38, 95% CI [0.19, 0.76]) and varenicline use (OR = 0.30, 95% CI [0.11, 0.78]) were protected against marked weight gain, whereas presence of a comorbidity (OR = 3.33, 95% CI [1.10, 10.00]), high level of nicotine dependence at baseline (OR = 2.07, 95% CI [1.09, 3.92]), and successfully quitting smoking (OR = 4.57, 95% CI [1.94, 10.08]) were associated with marked weight gain. DISCUSSION: Understanding the factors associated with weight gain after smoking cessation can help in the design of nursing interventions to lessen or prevent weight gain among smokers who try to quit.

Comparison of antibiotic use and antibiotic resistance between a community hospital and tertiary care hospital for evaluation of the antimicrobial stewardship program in Japan.

Assessment of risk-adjusted antibiotic use (AU) is recommended to evaluate antimicrobial stewardship programs (ASPs). We aimed to compare the amount and diversity of AU and antimicrobial susceptibility of nosocomial isolates between a 266-bed community hospital (CH) and a 963-bed tertiary care hospital (TCH) in Japan. The days of therapy/100 bed days (DOT) was measured for four classes of broad-spectrum antibiotics predominantly used for hospital-onset infections. The diversity of AU was evaluated using the modified antibiotic heterogeneity index (AHI). With 10% relative DOT for fluoroquinolones and 30% for each of the remaining three classes, the modified AHI equals 1. Multidrug resistance (MDR) was defined as resistance to ≥ 3 anti-Pseudomonas antibiotic classes. The DOT was significantly higher in the TCH than in the CH (10.85 ± 1.32 vs. 3.89 ± 0.93, p < 0.001). For risk-adjusted AU, the DOT was 6.90 ± 1.50 for acute-phase medical wards in the CH, and 8.35 ± 1.05 in the TCH excluding the hematology department. In contrast, the DOT of antibiotics for community-acquired infections was higher in the CH than that in the TCH. As quality assessment of AU, higher modified AHI was observed in the TCH than in the CH (0.832 ± 0.044 vs. 0.721 ± 0.106, p = 0.003), indicating more diverse use in the TCH. The MDR rate in gram-negative rods was 5.1% in the TCH and 3.4% in the CH (p = 0.453). No significant difference was demonstrated in the MDR rate for Pseudomonas aeruginosa and Enterobacteriaceae species between hospitals. Broad-spectrum antibiotics were used differently in the TCH and CH. However, an increased antibiotic burden in the TCH did not cause poor susceptibility, possibly because of diversified AU. Considering the different patient populations, benchmarking AU according to the facility type is promising for inter-hospital comparisons of ASPs.

Relationship between the strength of craving as assessed by the Tobacco Craving Index and success of quitting smoking in Japanese smoking cessation therapy.

BACKGROUND: We previously developed the Tobacco Craving Index (TCI) to assess craving of smokers. In the present study, we validated the relationship between the TCI grade over the 5 sessions of Japanese smoking cessation therapy (SCT) and success of quitting smoking among 889 Japanese patients. METHODS: The Japanese SCT consists of 5 sessions of SCT (first session and sessions 2, 4, 8 and 12 weeks later). In the TCI questionnaire, patients are asked to rate their strength of craving and frequency of craving, each on a four-point Likert scale. Patients are classified into one of four grades based on their responses (0, I, II, III, with III indicating severe craving). The TCI questionnaire was administered to each participant at each session of the SCT. This study included participants of Japanese SCT who answered the TCI at the first session of the SCT at five Japanese smoking cessation clinics. Patients who dropped out of the SCT from the second to the fifth sessions were considered to have failed smoking cessation. To elucidate how much the TCI grade predicts smoking status at the last session, we performed multivariate logistic regression analysis with adjustment for confounding factors. RESULTS: Participants who had higher TCI grade(III) in the 2nd through 5th sessions showed significantly lower probability for success of quitting smoking than those who had lower TCI grades(0 or I) (adjusted odds ratio: 2nd session: 0.30, 3rd session: 0.15, 4th session: 0.06, 5th session: 0.02). CONCLUSIONS: We validated the usefulness of the TCI grade for assessing probability of quitting smoking by using a large number of smoking cessation settings.

[Efficacy and safety of continuous subcutaneous injection of the compound oxycodone in cancer pain management: the first 4-year audit].

The compound oxycodone injection, but not pure oxycodone, has been available since the 1920's in Japan. The compound, containing oxycodone and hydrocotarnine, can be subcutaneously administered. Hydrocotarnine is a non-narcotic opium alkaloid. Nowadays, along with the increase in the prescription frequency of oral oxycodone, the compound oxycodone injection is regarded as an important alternative in palliative care. However, few clinical reports about this drug have been documented in Japan. We have intensively introduced the compound for cancer pain control since 4 years ago and we report a study on the safety and efficacy of the continuous subcutaneous administration of the compound injection. Ninety-seven patients were naively administered the compound for cancer pain control and the mean administered period was 18. 0+/-15. 5 days. 61. 9% of all cases were switched from oral oxycodone. The efficacy in cancer pain control was evaluated for the first two weeks using a numeric rating scale (NRS: 0, no pain, and 10, imaginary worst ). They had statically shown pain control improvement from 6. 8+/-2. 8 on administration to 2. 4+/-2. 5 one week later, 1. 7+/-1. 9 two weeks later, and 2. 3 +/-2. 6 on the last observation day of the study (p<0. 001). One week later on administration, no significant adverse effects were found in the serology, conscious level, and subjective symptoms of nausea and vomiting. But adverse effects difficult to manage were experienced in 7. 2%, including delirium, constipation, nausea and vomiting, vertigo, and local skin toxicity on the injected site. All episodes were experienced within 16 days of compound administration, which had been followed by switching to fentanyl or subcutaneous morphine injection. The conversion ratio from compound oxycodone injection to oral oxycodone was 1. 43 without adjustment required(n=35). We speculate that the compound can be regarded as a pure oxycodone injection using continuous subcutaneous administration. While our clinical audit is a primitive one, we may conclude that the continuous subcutaneous administration of the compound oxycodone injection should be effective and safe in clinical use for cancer pain control.

Necrotizing tracheobronchitis associated with rheumatoid arthritis.

We report a case of necrotizing tracheobronchitis with rheumatoid arthritis. A 64 year-old-man presented with dry cough and was initially diagnosed with community-acquired pneumonia. The patient was admitted; he received initial antibiotic treatment. The treatment was effective and the symptoms worsened. Bronchoscopy was performed for more thorough examination. It showed that white and soft tissues were on the trachea-bronchus. Transbronchial biopsy of the tracheal lesions revealed necrotic tissue with squamous metaplasia and inflammatory cells. Whereas, symmetrical arthralgia of multiple joints of the limbs was noted and rheumatoid factor and anti-cyclic citrullinated peptide antibody of levels were high. According to these results, the patient was diagnosed with rheumatoid arthritis. In this case, necrotizing tracheobronchitis occurred as a result of systemic inflammation associated with rheumatoid arthritis. An acute exacerbation of the patient's respiratory condition was treated with steroid therapy. Tracheal findings and respiratory symptoms were improved by steroid therapy.

Can we predict the development of serious adverse events (SAEs) and early treatment termination in elderly non-small cell lung cancer (NSCLC) patients receiving platinum-based chemotherapy?

PURPOSE: Predicting the feasibility of platinum-based chemotherapy remains an important issue in elderly (over 70 years) patients with non-small cell lung cancer (NSCLC). The aim of this study was to identify the risk factors for the early serious adverse events (SAEs) (during cycles 1-2) in elderly receiving platinum-based chemotherapy, and to explore the clinical characteristics of patients who require early treatment termination without progressive disease (PD). METHODS: One hundred and ninety-eight consecutive elderly NSCLC patients receiving platinum-based chemotherapy were retrospectively reviewed. RESULTS: The median age was 73 years (range 70-83). 161 (81 %) were males, and 190 (95 %) were PS 0-1. Fifty-one (29 %) and 39 (19 %) patients developed early non-hematological SAEs and hematological SAEs, respectively. Multivariate analysis identified low serum albumin (<3.0 g/dl) as an independent risk factor for non-hematological SAEs, while low creatinine clearance (<45 ml/min) for hematological SAEs. In all, 24 (12 %) patients needed early treatment termination without PD. The major reason for this event was the development of non-hematological SAEs (4.5 %), followed by grade 2 non-hematological adverse events (AEs) (3 %). In multivariate analysis, age over 75 years and low serum albumin were associated with this event. The median overall survival (OS) in patients with this event was only 6.0 months, while the development of early SAE was not associated with poor OS. CONCLUSION: Baseline serum albumin might be useful for predicting the feasibility of platinum-based chemotherapy, and the risk estimation of early treatment termination without PD might be beneficial for the treatment selection in elderly NSCLC patients.

[A rare case of disseminated Mycobacterium kansasii infection].

Mycobacterium kansasii infection has been reported to be about 20 percent of non-tuberculous mycobacteriosis, and its disseminated type is uncommon and the prognosis is reported to be generally poor. We experienced one case of disseminated Mycobacterium kansasii infection. A 81 year-old man who had been short-bowel syndrome due to the operation for superior mesenteric artery occlusion since 1998 was admitted on April 24th, 2001 to our hospital because of slowly progressive consciousness disturbance and anorexia. He had shown progressive productive cough and respiratory failure and laboratory findings were C-reactive protein elevation and pancytopenia. Human immunodeficiency virus (HIV) antibody was negative. Chest X-ray and computed tomography showed diffuse miliary nodules and infiltrative shadow. Sputum examination was positive for mycobacteria. The cultured isolate was identified as Mycobacterium kansasii. Bone marrow aspirations revealed inflammatory granuloma with necrosis. He was diagnosed as disseminated Mycobacterium kansasii infection and heart failure, and was treated by anti-tuberculosis drugs and diuretics. Treatment was very effective and Chest X-ray findings and respiratory failure had been completely improved. In this case we speculated that the malnutrition due to short-bowel syndrome could be one of the most suspected reasons of Mycobacterium kansasii dissemination. Disseminated Mycobacterium kansasii infection has been rarely reported comparing with the other mycobacterial infections in Japan. However, due to the increasing numbers of immunocompromised hosts with aging, HIV infection, cancer, and steroid therapy, this type of infection will become more common and its earlier diagnosis and adequate treatment will be important to improve the prognosis.

Gender-based differences in bleomycin-induced pulmonary fibrosis.

The role of gender and sex hormones is unclear in host response to lung injury, inflammation, and fibrosis. To examine gender influence on pulmonary fibrosis, male and female rats were given endotracheal injections of either saline or bleomycin. Female rats showed higher mortality rates and more severe fibrosis than did male rats, as indicated by higher levels of lung collagen deposition and fibrogenic cytokine expression. To clarify the potential role of female sex hormones in lung fibrosis, female rats were ovariectomized and treated with either estradiol or vehicle plus endotracheal injections of either saline or bleomycin. The results showed diminished fibrosis in the ovariectomized, bleomycin-treated rats without hormone replacement. Estradiol replacement restored the fibrotic response to that of the intact female mice in terms of lung collagen deposition and cytokine expression, which was accompanied by higher plasma estradiol levels. Furthermore, fibroblasts from bleomycin-treated rats exhibited increased responsiveness to estradiol treatment, causing dose-dependent increases in procollagen 1 and transforming growth factor-beta1 mRNA expression relative to untreated controls. Taken together these findings suggest that female mice may have an exaggerated response to lung injury relative to male mice because of female sex hormones, which have direct fibrogenic activity on lung fibroblasts. This may provide a mechanism for a hormonally mediated intensification of pulmonary fibrosis.

Regulation of telomerase activity in rat lung fibroblasts.

Fibroblasts from bleomycin-injured lungs express telomerase activity transiently during the period of active fibrosis, but the signal(s) responsible for its induction is (are) unknown. The objective of this study was to identify potential mediators capable of regulating telomerase activity induction in rat lung fibroblasts during pulmonary fibrosis. Lung fibroblasts from control (NRF) and bleomycin-treated (BRF) rats were isolated and treated in vitro with either basic fibroblast growth factor (bFGF) or interleukin-4 (IL-4). At selected time points after treatment, the cells were analyzed for telomerase activity, as well as telomerase reverse transcriptase (TERT) mRNA and protein by reverse transcriptase/polymerase chain reaction and Western blot, respectively. The results showed that bFGF could induce telomerase activity in NRF and stimulate further the induced activity in BRF. The bFGF effect was accompanied by increased TERT protein expression and a rapid but transient increase in TERT mRNA. In contrast, IL-4 inhibited the induced telomerase activity in BRF, which was accompanied by increased alpha-smooth muscle actin expression, an indicator of myofibroblast differentiation. These findings suggest that telomerase expression could be induced in rat lung fibroblasts by bFGF, but suppressed by IL-4, which promoted myofibroblast differentiation. The latter is consistent with the preferential expression of telomerase activity in fibroblasts relative to myofibroblasts.