PIN1 is a new therapeutic target of craniosynostosis.

Gain-of-function mutations in fibroblast growth factor receptors (FGFRs) cause congenital skeletal anomalies, including craniosynostosis (CS), which is characterized by the premature closure of craniofacial sutures. Apert syndrome (AS) is one of the severest forms of CS, and the only treatment is surgical expansion of prematurely fused sutures in infants. Previously, we demonstrated that the prolyl isomerase peptidyl-prolyl cis-trans isomerase interacting 1 (PIN1) plays a critical role in mediating FGFR signaling and that Pin1+/- mice exhibit delayed closure of cranial sutures. In this study, using both genetic and pharmacological approaches, we tested whether PIN1 modulation could be used as a therapeutic regimen against AS. In the genetic approach, we crossbred Fgfr2S252W/+, a mouse model of AS, and Pin1+/- mice. Downregulation of Pin1 gene dosage attenuated premature cranial suture closure and other phenotypes of AS in Fgfr2S252W/+ mutant mice. In the pharmacological approach, we intraperitoneally administered juglone, a PIN1 enzyme inhibitor, to pregnant Fgfr2S252W/+ mutant mice and found that this treatment successfully interrupted fetal development of AS phenotypes. Primary cultured osteoblasts from Fgfr2S252W/+ mutant mice expressed high levels of FGFR2 downstream target genes, but this phenotype was attenuated by PIN1 inhibition. Post-translational stabilization and activation of Runt-related transcription factor 2 (RUNX2) in Fgfr2S252W/+ osteoblasts were also attenuated by PIN1 inhibition. Based on these observations, we conclude that PIN1 enzyme activity is important for FGFR2-induced RUNX2 activation and craniofacial suture morphogenesis. Moreover, these findings highlight that juglone or other PIN1 inhibitors represent viable alternatives to surgical intervention for treatment of CS and other hyperostotic diseases.

Hyperprogressive disease during PD-1/PD-L1 blockade in patients with non-small-cell lung cancer.

BACKGROUND: Immune checkpoint blockade with Programmed cell death 1 (PD-1)/PD-L1 inhibitors has been effective in various malignancies and is considered as a standard treatment modality for patients with non-small-cell lung cancer (NSCLC). However, emerging evidence show that PD-1/PD-L1 blockade can lead to hyperprogressive disease (HPD), a flair-up of tumor growth linked to dismal prognosis. This study aimed to evaluate the incidence of HPD and identify the determinants associated with HPD in patients with NSCLC treated with PD-1/PD-L1 blockade. PATIENTS AND METHODS: We enrolled patients with recurrent and/or metastatic NSCLC treated with PD-1/PD-L1 inhibitors between April 2014 and November 2018. Clinicopathologic variables, dynamics of tumor growth, and treatment outcomes were analyzed in patients with NSCLC who received PD-1/PD-L1 blockade. HPD was defined according to tumor growth kinetics (TGK), tumor growth rate (TGR), and time to treatment failure (TTF). Immunophenotyping of peripheral blood CD8+ T lymphocytes was conducted to explore the potential predictive biomarkers of HPD. RESULTS: A total of 263 patients were analyzed. HPD was observed in 55 (20.9%), 54 (20.5%), and 98 (37.3%) patients according to the TGK, TGR, and TTF. HPD meeting both TGK and TGR criteria was associated with worse progression-free survival [hazard ratio (HR) 4.619; 95% confidence interval (CI) 2.868-7.440] and overall survival (HR, 5.079; 95% CI, 3.136-8.226) than progressive disease without HPD. There were no clinicopathologic variables specific for HPD. In the exploratory biomarker analysis with peripheral blood CD8+ T lymphocytes, a lower frequency of effector/memory subsets (CCR7-CD45RA- T cells among the total CD8+ T cells) and a higher frequency of severely exhausted populations (TIGIT+ T cells among PD-1+CD8+ T cells) were associated with HPD and inferior survival rate. CONCLUSION: HPD is common in NSCLC patients treated with PD-1/PD-L1 inhibitors. Biomarkers derived from rationally designed analysis may successfully predict HPD and worse outcomes, meriting further investigation of HPD.

Locoregional relapse after gastrectomy with D2 lymphadenectomy for gastric cancer.

BACKGROUND: Risk for and site of locoregional relapse have not been well studied in patients undergoing gastrectomy with D2 lymphadenectomy for gastric cancer. METHODS: Patients who had undergone gastrectomy with D2 lymphadenectomy for gastric cancer between 2004 and 2007 were identified from an institutional database. The locoregional relapse rate was estimated by competing risk analysis, and risk groups were derived according to locoregional relapse risk using recursive partitioning analysis (RPA). The locations of nodal relapses were evaluated according to Japanese Classification of Gastric Carcinoma criteria. RESULTS: Some 2618 patients were included. With a median follow-up of 78·0 (range 28·5-122·6) months, relapse was diagnosed in 471 of 2618 patients (18·0 per cent). The cumulative incidence of locoregional relapse at 5 years was 8·5 (95 per cent c.i. 7·4 to 9·6) per cent. The 5-year locoregional recurrence rates for high-risk (N3), intermediate-risk (N1-2) and low-risk (N0) groups were 32·4, 12·3 and 1·7 per cent respectively (P < 0·001). Among patients with regional relapse, 90·4 per cent had involvement outside the D2 dissected area, and the most commonly involved site was station 16b1. This pattern was maintained in the RPA risk groups (P = 0·329). CONCLUSION: Locoregional relapse at 5 years after gastrectomy with D2 lymphadenectomy was 8·5 per cent, and was most often seen outside the D2 dissected area.

Tumor-related leukocytosis is associated with poor radiation response and clinical outcome in uterine cervical cancer patients.

BACKGROUND: To evaluate response to radiation and clinical outcome of uterine cervical cancer patients with tumor-related leukocytosis (TRL) at initial diagnosis and during definitive radiotherapy. PATIENTS AND METHODS: We retrospectively analyzed 2456 patients with stage IA-IVA uterine cervical cancer who received definitive radiotherapy with (37.4%) or without (62.6%) platinum-based chemotherapy between 1986 and 2012. TRL was defined as two or more occurrences of leukocytosis over 9000/µl at the time of diagnosis and during the course of treatment. Locoregional failure-free survival (LFFS) and overall survival (OS) were compared between patients with or without TRL. RESULTS: The median age of all patients was 55 years, and the median follow-up time was 65.1 months. TRL was observed in 398 patients (16%) at initial diagnosis; TRL (+) patients were younger and had larger tumors, advanced stage, and more frequent lymph node metastases (all P < 0.05). TRL (+) patients showed a significantly lower rate of complete remission than TRL (-) patients (89.9% versus 96.3%, respectively, P = 0.042). Ten-year LFFS and OS for all patients were 84% and 78%, respectively. LFFS and OS were significantly lower in TRL (+) patients than TRL (-) patients (10-year LFFS: 69% versus 87% respectively, P < 0.001; 10-year OS: 63% versus 81% respectively P < 0.001). After propensity score matching, LFFS and OS rates in TRL (+) patients remained significantly lower than for TRL (-) patients; this significant difference was also observed on multivariate analysis. Twenty-six percent of patients with locoregional failure (n = 345) were TRL (+) and had significantly poorer median OS (6 versus 12 months, P = 0.001). CONCLUSION: This study reveals the aggressive nature of cervical cancer with TRL and its poor response to radiation therapy. Given the unfavorable prognosis and higher probability of treatment failure, optimal diagnostic and therapeutic approaches and careful monitoring for early detection of recurrence should be considered for these patients.

Comparison of propofol and the combination of propofol and alfentanil during bronchoscopy: a randomized study.

BACKGROUND: propofol is an excellent sedative agent for use in patients undergoing bronchoscopy. The addition of an opioid to propofol can be advantageous because of the antitussive effect of the opioid and the possible improvement in sedation quality. However, it may increase the risk of hypoxaemia. To investigate the effect of the addition of alfentanil to propofol, we performed a prospective study to compare propofol-only sedation with propofol-alfentanil combination sedation in patients undergoing bronchoscopy. METHODS: patients were randomly assigned either to the propofol-only (group P, n=32) or to the propofol-alfentanil combination group (group PA, n=32). The average peripheral oxygen saturation (SpO(2) ) and the lowest SpO(2) during the sedation were compared. Patient and bronchoscopist satisfaction as well as the degree of coughing were compared using a 100 mm visual analogue scale, where 0 indicated the least and 100 indicated the most satisfied. RESULTS: group P had the higher average SpO(2) (%) during the procedure than group PA (97.8 ± 1.6 and 96.4 ± 1.1, P<0.01) as well as the lowest SpO(2) (%) (95.4 ± 2.7 and 94.0 ± 2.4, P<0.05). Patient satisfaction (92.2 ± 13.5 and 92.3 ± 18.2), bronchoscopist satisfaction (76.6 ± 18.1 and 72.8 ± 19.1), and degree of cough (73.4 ± 22.7 and 72.2 ± 18.5; group P and group PA, respectively) were not different between the groups. CONCLUSIONS: the combination of propofol and alfentanil resulted in a greater respiratory depression than propofol alone; furthermore, the addition of an opioid did not improve the quality of sedation. In conclusion, we do not recommend sedation with propofol and alfentanil during bronchoscopy.

Nested PCR in lung tissue for diagnosis of pulmonary tuberculosis.

Diagnosis of pulmonary tuberculosis (TB) is difficult in cases with an unusual presentation and often requires a lung biopsy. The goal of this study was to determine the clinical usefulness of nested PCR on lung tissue for the diagnosis of pulmonary TB. Clinical and laboratory data were reviewed from patients who underwent diagnostic lung biopsies, followed by nested TB PCR on formalin-fixed paraffin-embedded lung tissue specimens. The diagnostic yield and clinical impact of nested PCR were investigated. Of the 223 patients studied, 142 were diagnosed with TB. Microbiologically confirmed TB was identified in 71 patients. Compared to culture results, the sensitivity, specificity, positive predictive value and negative predictive value of nested PCR were 85%, 99%, 98% and 88%, respectively. Nested PCR was more sensitive than acid-fast bacilli smear of respiratory specimens and histopathological findings. The PCR results provided an early diagnosis and initiation of treatment for TB. However, negative PCR results did not lead to discontinuation of unnecessary TB treatment in patients on medication. In conclusion, nested PCR on lung tissue specimens is a useful diagnostic test for pulmonary TB in patients with an unusual presentation.

Exposure to volatile organic compounds and loss of pulmonary function in the elderly.

Volatile organic compounds (VOCs) are reported to cause adverse effects on pulmonary function in occupationally exposed workers. However, evidence is lacking on the effect in the general population. We hypothesised that VOCs impair pulmonary function through enhancing oxidative stress, especially in the elderly population. A longitudinal panel study of 154 elderly people was performed in South Korea. Repeated spirometric tests were performed up to eight times on different days for each subject. We also measured urinary concentrations of metabolites of the VOC and markers of oxidative stress (malondialdehyde and 8-oxo-2'-deoxyguanosine) on the same day of spirometric tests. A mixed linear regression model was used to evaluate the association among the VOC metabolites, oxidative stress markers and spirometric tests. We found that the urinary levels of hippuric acid and methylhippuric acid, which are metabolites of toluene and xylene, respectively, were significantly associated with reduction of forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity (FVC), and forced expiratory flow at 25-75% of FVC. We also found significant associations between the metabolites of VOCs and the markers of oxidative stress. In addition, the oxidative stress markers were associated with pulmonary function parameters. This study suggests that exposure to toluene and xylene exert a harmful effect on pulmonary function by exacerbating oxidative stress in elderly people.

A case of systemic polyarteritis nodosa involving bronchial artery.

Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis involving predominantly medium-sized muscular arteries. It commonly involves skin, kidney, cardiovascular system, gastrointestinal system, and neurological system. But bronchial artery involvement of PAN is rarely identified. We report a case of PAN with initial presentation of hemoptysis. On admission, chest radiograph and chest CT angiography revealed no focus of bleeding. Angiography showed a bronchial artery aneurysm and multiple arterial aneurysms in both renal, hepatic, mesenteric and branches of small bowel arteries. These findings were compatible with the diagnosis of PAN. The patient was started on steroid and cyclophosphamide.

Diagnostic value of bronchoalveolar lavage and bronchial washing in sputum-scarce or smear-negative cases with suspected pulmonary tuberculosis: a randomized study.

OBJECTIVES: Bronchoalveolar lavage (BAL) and bronchial washing (BW) are two major methods used to obtain high-quality respiratory specimens from patients with suspected pulmonary tuberculosis (TB) but a sputum-scarce or smear-negative status. We aimed to compare the value of BAL and BW in the diagnosis of TB in such patients. METHODS: We enrolled patients with suspected pulmonary TB but with a sputum-scarce or smear-negative status who were referred for bronchoscopy between October 2013 and January 2016. Participants were randomized into the BAL and BW groups for evaluation. The primary outcome was the diagnostic yield for TB detection. Secondary outcomes included culture positivity, positivity of nucleic acid amplification tests (NAATs) for Mycobacterium tuberculosis and procedure-related complications. RESULTS: A total of 94 patients were assessed and 91 (43 in the BAL group, 48 in the BW group) were analysed. Twenty-one patients (48.8%) in the BAL group and 30 (62.5%) in the BW group had a final diagnosis of pulmonary TB. The detection rate of M. tuberculosis by culture or NAAT was significantly higher in BAL specimens than in BW specimens (85.7% vs 50.0%, p 0.009). The procedure-related complications were hypoxic events, 2/43 (4.7%) in the BAL group and 5/48 (10.4%) in the BW group; and post-bronchoscopic fever, 3/43 (7.0%) in the BAL group and 4/48 (8.3%) in the BW group. DISCUSSION: As long as it is tolerable, BAL rather than BW, should be used to obtain specimens for the diagnosis of pulmonary TB in sputum-scarce or smear-negative cases.

Distinctive patterns of pulmonary function change according to baseline lung volume and diffusing capacity.

SETTING: Multicentre retrospective study in South Korea.OBJECTIVE: To longitudinally evaluate changes in lung volume and diffusing capacity for carbon monoxide (DLCO) with forced expiratory volume in 1 sec (FEV1).DESIGN: A total of 155 patients with chronic obstructive pulmonary disease (COPD), whose pulmonary function parameters were measured annually for 5 years, were selected from a prospective cohort in South Korea. A random coefficients model was used to estimate mean annual FEV1, lung volume parameter and DLCO change rates.RESULTS: Patients were classified into four groups based on baseline DLCO and residual volume/total lung capacity (RV/TLC) measurements. The annual FEV1 decline rate was greater in patients with low DLCO than in those with normal DLCO, with the greatest decline occurring in patients with low DLCO and normal RV/TLC. RV and RV/TLC declined in patients with high RV/TLC, whereas these increased in patients with normal RV/TLC. DLCO decreased longitudinally in all four groups, with the greatest decline occurring in patients with normal DLCO and normal RV/TLC.CONCLUSIONS: Different subgroups of patients with COPD exhibited distinctive pulmonary function change patterns. Baseline DLCO and RV/TLC may be used as physiological markers to predict long-term changes in pulmonary function.

Nutritional deficit as a negative prognostic factor in patients with miliary tuberculosis.

The effects of malnutrition on outcomes in miliary tuberculosis (MTB) are not well described. The aim of the present study was to find predictors for the development of acute respiratory failure (ARF) and survival in MTB patients, focusing on parameters reflecting nutritional condition. Out of the patients from three hospitals who had microbiologically or histopathologically confirmed tuberculosis, 56 patients presenting with typical disseminated pulmonary nodules on radiographs were retrospectively enrolled. A four-point nutritional risk score (NRS) was defined according to the presence of four nutritional factors: low body mass index (BMI; <18.5 kg x m(-2)), hypoalbuminaemia (<30.0 g x L(-1)), hypocholesterolaemia (<2.33 mmol x L(-1)) and severe lymphocytopenia (<7 x 10(5) cells x L(-1)). The male to female ratio was 1:3. ARF developed in 25% of patients (14 out of 56), with a 50% fatality rate. A high NRS (> or =3 points) was an independent risk factor for the development of ARF and fatality. In 90-day survival analysis, ARF, severe lymphocytopenia, hypocholesterolaemia, low BMI and higher NRS were risk factors for poor outcome. In multivariate analysis, only high NRS was an independent risk factor for 90-day survival rate in patients with MTB. A high nutritional risk score was a good predictor of poor outcome in miliary tuberculosis patients. Additional approaches to recover the nutritional deficits may become a focus in future management of miliary tuberculosis.

Low serum concentrations of anti-tuberculosis drugs and determinants of their serum levels.

SETTING: Low serum concentrations of anti-tuberculosis drugs have occasionally been associated with treatment failure. OBJECTIVE: To determine the prevalence of low serum concentrations of anti-tuberculosis drugs and to identify the determinants of drug concentrations. DESIGN: Venous blood was obtained 2 h after drug ingestion, and serum levels of isoniazid (INH), rifampicin (RMP), ethambutol (EMB), pyrazinamide (PZA), acetyl INH and 25-desacetyl RMP were analysed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Patients with human immunodeficiency virus co-infection and gastrointestinal disease or diarrhoea were excluded. RESULTS: Among 69 enrolled TB patients, the prevalence of a low 2 h serum concentration of at least one anti-tuberculosis drug was 46.4%. Prevalences of a low concentration of INH, RMP, EMB or PZA were 15.2%, 23.5%, 22.4% and 4.5%, respectively. By multivariate linear regression analysis, the serum concentrations of INH, RMP and PZA were positively associated with dose per kg of body weight (P < 0.05). Moreover, INH concentration was associated with acetyl INH/INH ratio (beta = -8.588, P < 0.001) and EMB concentration was associated with calculated creatinine clearance (beta = -0.025, P < 0.001). CONCLUSION: Low concentrations of anti-tuberculosis drugs are common, and although the clinical significance of low concentrations remains uncertain, it may be necessary to optimise drug doses by therapeutic drug monitoring, especially in patients with an inadequate clinical response to chemotherapy.

Determinants of diagnostic bronchial washing in peripheral lung cancers.

OBJECTIVE: To establish clinical determinants affecting the diagnostic yield of bronchial washing. SETTING: We performed bronchial washing in 241 consecutive patients with bronchoscopically invisible lung tumours. Of these, 150 patients known to have lung cancer were enrolled for the final analysis. DESIGN: A multi-centre study. RESULTS: Bronchial washing provided a diagnosis of lung cancer in 30 of the 150 patients (20%). Tumour size > or = 3 cm (P = 0.005), the location of the tumour within 8 cm of the carina (P = 0.003), and exposed type bronchus sign of tumour (P < 0.001) were factors affecting diagnostic bronchial washing for bronchoscopically invisible lung cancers. However, multivariate logistic regression revealed that exposed type bronchus sign was the sole determinant (OR 19.22, 95% CI 4.23-87.46, P < 0.001). CONCLUSION: Bronchial washing is a useful procedure for the diagnosis of bronchoscopically invisible lung cancers. As the tumour-bronchus relationship is the most important determinant of a diagnostic yield, the routine use of bronchial washing should be considered for tumours with exposed type bronchus sign.

Integration of radiotherapy and chemotherapy for abdominal lymph node recurrence in gastric cancer.

PURPOSE: Abdominal lymph node (ALN) recurrence in gastric cancer (GC) is rare and usually unresectable. We investigated the effects of integration of radiotherapy (RT) and chemotherapy against ALN recurrence in GC. METHODS: We retrospectively categorized GC patients with ALN recurrence treated between 2005 and 2013 into two groups: those treated with integration of RT and chemotherapy (RCT) and those who received systemic chemotherapy only (CT). The median follow-up period after ALN recurrence for all patients was 20 months. RESULTS: Of 53 patients, 31 and 22 were in the RCT and CT groups, respectively. Isolated distant failure (DF; 35.5%) without local progression (LP) was the dominant pattern of failure (POF) in the RCT group (median DF-free period, 26 months). LP followed by DF (31.8%) was the dominant POF in the CT group; LP (median LP-free period, 8 months) occurred 10 months earlier than DF (median DF-free period, 18 months). RCT patients had significantly longer median progression-free survival (PFS) compared to CT patients (25 vs. 8 months; P = 0.021). On multivariate analysis, treatment (CT vs. RCT) was an independent prognostic factor for PFS (hazard ratio 2.085; 95% confidence interval 1.073-4.050; P = 0.013). CONCLUSIONS: Integration of RT and chemotherapy achieved long-term local control and prolonged PFS in GC patients with ALN recurrence. Local RT is feasible for treating isolated ALN recurrences.

Bronchial angles are associated with nodular bronchiectatic non-tuberculous mycobacteria lung disease.

BACKGROUND: The nodular bronchiectatic (NB) form of non-tuberculous mycobacteria (NTM) lung disease usually involves the right middle lobe (RML) and the left upper lobe lingular segment. However, the reason underlying this preference is not known. METHODS: Fifty patients with NB NTM lung disease who had both positive NTM culture(s) and NB lesions in the RML or lingular segment on computed tomography (CT) of the chest, and 100 healthy subjects matched for sex, age, height and body weight with normal chest CT, were randomly selected. Using reconstructed curved multiplanar reformation (MPR) images, the lengths, diameters and angles of the RML and lingular bronchi were measured. RESULTS: Of the 150 individuals, 64% were female; the mean age was 55 years. The angles of the bronchi were significantly more acute in patients than in healthy subjects, both in the RML (patients, mean 46.75° ± standard deviation 8.87° vs. healthy subjects, mean 51.73° ± 7.76°; P = 0.001) and in the lingular segments (patients, mean 26.94° ± 8.16° vs. healthy subjects, mean 34.65° ± 9.75°; P < 0.001). In addition, the angles of the bronchi in the involved segments were more acute than those in the non-involved segments, both in the RML and the lingular segments. There were no differences in the lengths and bronchi diameters between groups. CONCLUSIONS: An acute angle (obtuse slope) of RML/lingular bronchi could be an anatomical risk factor for NB NTM lung disease.

Lack of association between COPD and transforming growth factor-beta1 (TGFB1) genetic polymorphisms in Koreans.

OBJECTIVE: Many genetic variations have been suggested as genetic risk factors for the development of chronic obstructive pulmonary disease (COPD), including single nucleotide polymorphisms in the transforming growth factor-beta1 (TGFB1) gene. We attempted to elucidate the association between TGFB1 genetic polymorphisms and COPD among Koreans. DESIGN: The genotypes of 102 male patients with COPD and 159 volunteers with similar distributions of age, sex and smoking intensity, as well as normal pulmonary function, were determined for three previously associated TGFB1 single nucleotide polymorphisms (SNPs), -10807G/A (rs2241712) and -509T/C (rs1800469), located in or near the promoter, and 29T/C (rs1982073), located in exon 1 of the TGFB1 gene. RESULTS: No significant associations between COPD and the three TGFB1 SNPs could be identified. In addition, the haplotypes composed of three TGFB1 SNPs were not associated with the presence of COPD. CONCLUSION: These results differ from previous reports involving Caucasians, and might reflect racial differences in the pathogenesis of COPD.

Oral insertion of a flexible bronchoscope is associated with less discomfort than nasal insertion for Korean patients.

OBJECTIVE: The route of bronchoscope insertion varies between centres, without a firm rationale based on well-designed studies. We therefore compared nasal and oral insertion of a flexible bronchoscope and evaluated efficacy and patient satisfaction. DESIGN: Prospective randomised study of patients who underwent flexible bronchoscopy from May to September 2003 and who were randomly assigned to nasal and oral insertion approaches. RESULTS: Clinical characteristics, factors related to the procedure and patient satisfaction were analysed. In total, 307 patients were randomly assigned to the nasal (n = 158) or oral insertion groups (n = 149). No difference in baseline characteristics was identified between the groups. Insertion by the oral route was associated with a smaller amount of lidocaine use during the procedure (P = 0.04) and less frequent insertion site bleeding (P = 0.005). Patients assigned to oral insertion reported less discomfort during anaesthesia (P = 0.01) and scope insertion (P < 0.001), as well as less dyspnoea (P = 0.04) and coughing (P = 0.03). CONCLUSION: Oral insertion of a flexible bronchoscope was associated with less discomfort for patients than nasal insertion, although the route of insertion had no significant effect on outcome.

Impact of fluoroquinolones on the diagnosis of pulmonary tuberculosis initially treated as bacterial pneumonia.

OBJECTIVE: The excellent in vitro activity of fluoroquinolones against Mycobacterium tuberculosis has raised concerns about the delayed diagnosis of pulmonary tuberculosis (PTB) initially misdiagnosed as pneumonia. The aim of this study was to assess the effect of empiric fluoroquinolone therapy on delays in diagnosis in patients with PTB initially misdiagnosed as bacterial pneumonia. DESIGN: Patients with PTB initially treated as having community-acquired pneumonia and treated with fluoroquinolones for more than 5 consecutive days, from January 2000 to December 2004, were enrolled. As a control group, TB patients initially treated with nonfluoroquinolone antibiotics were enrolled. We reviewed the clinical data and compared treatment responses between the two groups. RESULTS: Nine patients in the fluoroquinolone group and 19 patients in the non-fluoroquinolone group were enrolled. In the fluoroquinolone group, eight patients (89%) improved clinically or radiographically, whereas only eight patients (42%) in the non-fluoroquinolone group improved (P = 0.04). The delay in initiation of anti-tuberculosis medication was longer in the fluoroquinolone group than in the non-fluoroquinolone group (43.1 - 40.0 vs. 18.7 +/- 16.9 days, P = 0.04). CONCLUSION: Delay in the initiation of anti-tuberculosis treatment is possible in patients administered fluoroquinolone and initially misdiagnosed as having bacterial pneumonia.