Low household income increases the risk of tuberculosis recurrence: a retrospective nationwide cohort study in South Korea.

OBJECTIVES: We assessed the impact of household income on tuberculosis (TB) recurrence and the long-term impact of TB on household income. STUDY DESIGN: This was a retrospective nationwide cohort study of patients with drug-susceptible TB (DS-TB) and TB recurrence. METHODS: Using the South Korean national TB cohort database, we identified a sub-set cohort of patients with newly diagnosed drug-susceptible TB between 2013 and 2016 and tracked their TB recurrence and longitudinal income data from 2007 to 2018. Income levels were evaluated as 'Medical aid' and quintile categories. To assess risk factors associated with TB recurrence, we used a sub-distribution hazard model, adjusting for the competing risks of death. RESULTS: Of 66,690 patients successfully treated with DS-TB, 2095 (3.1 %) experienced recurrence during a median follow-up of 39 months. The incidence of TB recurrence was 982.1/100,000 person-years, with 50.3 % of the recurrences occurring within 1 year of treatment completion. The risk of TB recurrence increased with decreasing income levels, with the highest risk observed in the lowest income group. The effect of income on TB recurrence was prominent in males but not in females. Overall, patients with TB recurrence experienced a linear decline in income levels, compared with those without recurrence. CONCLUSIONS: Household income during the initial TB episode was an important risk factor for TB recurrence, particularly in males.

Long-term mortality of patients with tuberculosis in Korea.

BACKGROUND: Long-term mortality following tuberculosis (TB) diagnosis in Korea remains unclear.METHODS: The present study used data from the National Health Insurance Service database, an extensive health-related database including most Korean residents. TB patients were identified using International Classification of Diseases, Tenth Revision coding (A15-19, U88.0-88.1) and the type of anti-TB drug(s) between 2003 and 2016. Long-term mortality and causes of death in TB patients were analysed.RESULTS: A total of 357 211 individuals had TB over the period from 2003 to 2016 and 103 682 died. The mean age of the cohort was 54.7 ± 20.7 years, and 59.8% were male. The survival probability of TB patients at 1, 5, and 10 years after diagnosis was 87.8%, 75.3%, and 63.3%, respectively. High mortality and TB-related death rates were especially prominent in the early stages after TB diagnosis. The overall standardized mortality ratio of TB patients to the general Korean population was 3.23 (95% confidence interval 3.21-3.25).CONCLUSION: Mortality in TB patients was especially high in the early stages of disease after TB diagnosis, and mostly due to TB. This figure was approximately three-times higher than the mortality rate in the general population.

An IFN-γ and TNF-α dual release fluorospot assay for diagnosing active tuberculosis.

OBJECTIVES: Currently available interferon (IFN)-γ-release assays (IGRA) cannot discriminate active tuberculosis (TB) from latent TB infection (LTBI), and so have limited clinical utility for diagnosing active TB. Since numbers of tumour necrosis factor (TNF)-α-producing T cells are highly correlated with active TB, we hypothesized that detecting IFN-γ- and/or TNF-α-producing T cells would overcome this limitation of IGRA. This study evaluated the diagnostic performances of the IFN-γ and TNF-α dual release fluorospot assay for active TB. METHODS: Adult patients with suspected TB including recent TB exposers were prospectively enrolled over a 28-month period. In addition to the conventional IGRA test (i.e. QuantiFERON-In-Tube), a fluorospot assay for detecting IFN-γ- and TNF-α-producing T cells was performed. The final diagnoses were classified by clinical category. Patients with confirmed or probable TB were regarded as active TB, and patients with not active TB were further classified as having not active TB with and without LTBI, based on the QuantiFERON-In-Tube results. RESULTS: A total of 153 patients including 45 with active TB and 108 with not active TB (38 LTBI vs. 70 not LTBI) were finally analysed. The sensitivity and specificity of the QuantiFERON-In-Tube assay for active TB were 84% (95% confidence interval (CI), 70-93) and 70% (95% CI 61-79), respectively. The IFN-γ/TNF-α dual release assay by fluorospot had substantially higher diagnostic specificity (94%) for diagnosing active TB than the IFN-γ single release assay (72%, p < 0.001), without compromising sensitivity (84% vs. 89%, p 0.79). CONCLUSIONS: The fluorospot-based IFN-γ/TNF-α dual release assay appears to be a simple and useful test for diagnosing active TB.

Relationship between smoking and spontaneously healed pulmonary TB on chest radiography in a South Korean population.

SETTING: The Korea National Health and Nutrition Examination Survey is a national, population-based, cross-sectional surveillance programme.OBJECTIVE: 1) To investigate the prevalence of spontaneously healed pulmonary tuberculosis (SHPTB) on chest radiographs (CXRs) in South Korea, as well as its demographic and clinical associations, and 2) to determine the relationship between SHPTB and smoking.DESIGN: People with normal findings on CXRs (n = 24 190) and those with SHPTB (n = 1863) were compared in univariate, bivariate and multivariate analyses with respect to smoking and demographic and clinical factors.RESULTS: The prevalence of SHPTB was 7.2%. The proportion of patients with SHPTB tended to be higher in males, people of older age, ever smokers, as well as people with low body mass index and low education level. In bivariate analysis, after adjustments for age and sex, SHPTB was found more often among ex-smokers (P = 0.005) and current smokers (P = 0.024) than in non-smokers. Multivariate analyses revealed increased relative odds for SHPTB with increased age (P < 0.001), male sex (P < 0.001) and ex-smoker status (P = 0.016). Passive smoking was also significantly associated with SHPTB (P = 0.022).CONCLUSION: In addition to increasing the risk of active TB and negatively affecting the outcome of TB treatment, smoking is also associated with SHPTB, as detected on CXRs.

Relationship between airway obstruction and C-reactive protein levels in a community-based population of Korea.

OBJECTIVE: To examine the relationship between high-sensitivity C-reactive protein (hs-CRP) levels and lung function in a community-based cohort of South Korea.DESIGN: The Ansung-Ansan cohort database (an ongoing prospective study of a community-based population) was used in the analysis. We defined airway obstruction as the ratio between forced expiratory volume in 1 sec:forced vital capacity ratio (FEV1:FVC) of <95% of the predicted value for a healthy person. We also used the serum level of hs-CRP as a marker of inflammation. Multivariate analysis was performed with adjustment for the clinical characteristics of the participants.RESULTS: A total of 5528 individuals were eligible for the study. The average age was 55.1 years, and 47.8% were males. The prevalence of airway obstruction was 9.0%, and the mean hs-CRP level was 1.51 mg/dl. Serum hs-CRP levels increased with the severity of airway obstruction, and the latter worsened with an increase in the hs-CRP level. In multivariate analysis, as the hs-CRP level increased, FEV1 and FVC decreased. A higher FEV1:FVC ratio was associated with lower hs-CRP levels in males.CONCLUSION: Higher hs-CRP levels were associated with decreased FEV1 and FVC in a general population of Korea. The FEV1:FVC ratio decreased with an increase in the hs-CRP level in males.

Treatment of latent tuberculous infection among health care workers at a tertiary hospital in Korea.

OBJECTIVE: To evaluate the acceptance of, adherence to, and outcomes of latent tuberculous infection (LTBI) treatment among health care workers (HCWs). DESIGN: This was a retrospective study in a tertiary hospital in Korea. From May to August 2017, 2190 HCWs simultaneously underwent a tuberculin skin test (TST) and interferon-gamma release assay (IGRA). LTBI was diagnosed if the TST induration was 10 mm or IGRA results were positive. RESULTS: Of 2190 HCWs tested, 1006 (45.9%) were diagnosed with LTBI. Of these, 655 (65.1%) HCWs visited out-patient clinics, 234 (35.7%) of whom were advised treatment by physicians. Among these, 120 (51.3%) accepted the physicians' recommendations. In general, HCWs who were older, male and smoked were less likely to visit out-patient clinics. Sixty (50%) HCWs received 3 months of isoniazid plus rifampicin (3HR) and 57 (47.5%) HCWs received 4 months of rifampicin (4R). The proportion of HCWs with 2 side effects (3HR 20% vs. 4R 7.0%, P = 0.041) and drug stoppage rate (3HR 20% vs. 4R 5.3%, P = 0.017) were higher in the 3HR group than in the 4R group. Of the 120 HCWs, 78 (65%) completed LTBI treatment. CONCLUSION: Overall, the acceptance and completion rate for LTBI treatment was not adequate. For effective LTBI management in HCWs, further programmatic strategies are needed.

Safety and efficacy of tuberculin skin testing with microneedle MicronJet600™ in healthy adults.

SETTING: Intradermal injection using a syringe and needle is generally accepted as the most accurate method for the tuberculin skin test (TST). However, the Mantoux technique using a conventional needle is often difficult to perform reliably, affecting testing results and safety. OBJECTIVE: We evaluated the efficacy and safety of a novel intradermal injection device, the MicronJet600(TM) microneedle, compared with conventional injection in terms of skin reactivity to the TST. DESIGN: A prospective, open-label clinical study was conducted. The TST was administered by both methods in the same subject. For pain assessment, participants filled in a visual analogue scale (VAS) after each TST. Any side effects due to TST or injections were observed. RESULTS: TST reaction rates (cut-off ⩾5 mm) from microneedles and needles were respectively 44.0% and 47.2%, with no significant difference between the two. Furthermore, agreement of positivity between the two methods was excellent with both 5 mm and 10 mm cut-off values. However, the level of pain experienced when microneedles were used for TST was significantly lower than with conventional needles. No adverse effects were attributed to the MicronJet device. CONCLUSION: The novel microneedle device used for TST in this study was effective, safe and less painful in healthy adult volunteers.

Disulfanyl peptide decreases melanin synthesis via receptor-mediated ERK activation and the subsequent downregulation of MITF and tyrosinase.

OBJECTIVE: Bioactive peptides are commonly used in cosmeceutical purpose. This study was performed to search for an effective and short hypopigmenting peptide using normal human melanocytes as a screening model. A peptide that exhibits multitarget activities will be a promising peptide. METHODS: Depigmenting effects were tested in normal human melanocytes. One peptide was selected, and signalling mechanism was investigated by Western blotting and immunofluorescent microscopic examination. RESULTS: A novel hypopigmenting peptide (dSHP) has been found to inhibit the production of melanin. This peptide significantly decreases tyrosinase activity but was not effective in a direct in vitro assay. It also induces the prolonged activation of ERK, and subsequently downregulates the levels of MITF. PD98059 abolished the dSHP-induced downregulation of MITF. These findings indicate that the dSHP-induced activation of ERK contributes to a reduced melanin synthesis via the downregulation of MITF. Fluorescent microscopic studies were consistent with such findings. Pertussis toxin reverses the downregulation of MITF, which means that the receptor-mediated ERK activation is involved. Moreover, it was also found that downregulation of MITF was clearly inhibited by lysosomal inhibitor (chloroquine). CONCLUSION: Novel tetrapeptide dSHP reduces the melanin synthesis by a receptor-mediated pathway. Furthermore, dSHP works by ERK activation and key transcription factor MITF degradation. Thus, it may be a good candidate as an effective hypopigmenting cosmetic agent.

Tuberculosis is frequently diagnosed within 12 months of diabetes mellitus.

BACKGROUND: Evidence regarding the effects of tuberculosis (TB) screening among patients with diabetes mellitus (DM) in intermediate TB burden countries is insufficient, and the most appropriate time point for TB screening is unclear. OBJECTIVE: To investigate trends in TB incidence among newly diagnosed DM patients. DESIGN: A retrospective cohort study of the claims database of the Health Insurance Review and Assessment Service in Korea was performed. Participants were newly diagnosed with type 2 DM in 2009. The study outcome was TB incidence between 2009 and 2011 among participants according to duration of type 2 DM. RESULTS: A cohort of 331,601 patients with newly diagnosed type 2 DM in 2009 was identified. During the 3-year follow-up period, 1533 patients were diagnosed with TB. The estimated incidence of TB among newly diagnosed type 2 DM patients was 18/10,000 patient-years (py) (95%CI 17.5-19.4). TB incidence was 33/10,000 py (95%CI 30.0-35.6) in the first 6 months, and 19/10,000 py (95%CI 16.5-20.6) in the following 6-month period. CONCLUSIONS: The risk of developing TB was increased among DM patients, particularly during the first 12 months after DM diagnosis.

The effects of statin use on the development of tuberculosis among patients with diabetes mellitus.

OBJECTIVE: To evaluate whether statin use affects the development of tuberculosis (TB) among patients with diabetes mellitus (DM). METHODS: This is a retrospective cohort study of patients with newly diagnosed type 2 DM based on the South Korean nationwide claims database. The participants were type 2 DM patients aged 20-99 years who were newly treated with anti-diabetic drugs between 1 January 2007 and 31 December 2010. Patients who had statin prescriptions before a diagnosis of diabetes or were diagnosed with TB before diabetes were excluded. RESULTS: Of 840,899 newly diagnosed type 2 DM patients, 281,842 (33.5%) patients were statin users and 559,057 (66.5%) were non-users. During the study period, 4075 [corrected] individuals were diagnosed with TB; the estimated incidence of TB in our cohort was 251/100,000 patient-years (95%CI 243-258). In comparison to non-TB patients, statin users were less frequent among TB patients (19.2% vs. 33.6%). After adjustment for potential baseline confounders, statin use was not associated with the development of TB in DM patients (aHR 0.98; 95%CI 0.89-1.07). CONCLUSIONS: TB development among newly diagnosed type 2 DM was considerable, and statin use among these diabetics was not associated with a protective effect on TB incidence.

Association between genetic variants in the IRGM gene and tuberculosis in a Korean population.

PURPOSE: To investigate immunity-related guanosine triphosphatase family M (IRGM) genetic variants associated with susceptibility to tuberculosis (TB) in a Korean population. METHODS: We conducted a prospective case-control study including 193 patients with active TB in Severance Hospital and 230 age- and sex-matched unrelated controls registered in Yonsei Cardiovascular Genome Center. Based on associations with other chronic inflammatory conditions, we analyzed the allele and genotype frequencies of rs72553867, rs10065172, and rs12654043 among patients with TB and healthy controls. RESULTS: The T allele of rs10065172 was significantly associated with protection against developing TB based on allele frequency [P = 0.042; odds ratio (OR) 0.75] and genotype distribution in the codominant model (P = 0.036; OR 0.73). CONCLUSIONS: This is the first study to identify a significant association between the IRGM single-nucleotide polymorphism (SNP) rs10065172 and susceptibility to active TB disease in an Asian population. The results suggest that IRGM genetic variants could be associated with susceptibility to active TB disease in the Korean population.

Association between vitamin D deficiency and tuberculosis in a Korean population.

BACKGROUND: Several in vitro studies have been conducted regarding the immunomodulatory and mycobactericidal roles of vitamin D in tuberculous infection. However, discrepancies exist among epidemiological studies. We compared vitamin D deficiency between patients with tuberculosis (TB) and healthy control subjects and identified risk factors for vitamin D deficiency. METHOD: This was an age- and sex-matched case-control analysis of 94 TB cohort and 282 Korean national survey participants. RESULTS: The median baseline 25-hydroxyvitamin D (25[OH]D) level in the TB group (9.86 ng/ml, IQR 7.19-14.15) was lower than in controls (16.03 ng/ml, IQR 12.38-20.30, P < 0.001). The prevalence of severe vitamin D deficiency was higher in patients with TB (51.1%) than in controls (8.2%, P = 0.001). The median 25(OH)D level increased from 11.40 ng/ml (IQR 7.85-15.73) to 13.18 ng/ml (IQR 10.60-19.71) after treatment completion (P = 0.037). On multivariate analysis, presence of TB and history of TB were independently associated with severe vitamin D deficiency. CONCLUSION: Patients with TB had a higher prevalence of vitamin D deficiency than control subjects in a Korean population. The median 25(OH)D level increased after TB treatment. Further studies are needed to establish a causal relationship.

Body mass index and fat free mass index in obstructive lung disease in Korea.

OBJECTIVE: To investigate the relationship between body mass index (BMI), fat free mass index (FFMI) and obstructive lung disease in Korea. DESIGN: Based on a large population-based, nationwide survey conducted in Korea, 822 subjects with airway obstruction and the same number of healthy control subjects were selected. Spirometry and dual-energy X-ray absorptiometry were used for analysis. RESULTS: Subjects with airway obstruction had a lower mean BMI and FFMI than the control group (23.6 vs. 23.9 kg/m(2) for BMI, P = 0.015 and 17.2 vs. 17.5 kg/m(2) for FFMI, P = 0.013); the BMI (P < 0.001) and FFMI (P < 0.001) values decreased significantly in subjects with severe airway obstruction. The proportion of subjects who were underweight or who had a low FFMI was significantly higher in the severe airway obstruction group (P < 0.001). The decrease in FFMI was more prominent in the lower extremities, followed by the upper extremities and the trunk. Subjects who were underweight had significantly lower one-second forced expiratory volume (FEV1; P = 0.001) and FEV1/forced vital capacity values (P < 0.001). CONCLUSION: We suggest that lower BMI and FFMI are associated with degree of airway obstruction and that the assessment of BMI and body composition is necessary in patients with severe airway obstruction.

Validation of a scoring tool to predict drug-resistant pathogens in hospitalised pneumonia patients.

BACKGROUND: Health care-associated pneumonia (HCAP) affects a heterogeneous group of patients in frequent contact with health care systems. However, HCAP criteria poorly predict infection with drug-resistant (DR) pathogens. OBJECTIVE: To validate our previously reported risk-scoring model (predictive of DR pathogen infection) in patients admitted to hospital with pneumonia. DESIGN: We evaluated 580 patients admitted with culture-positive bacterial pneumonia. We identified risk factors, evaluated the risk-scoring model's capacity to predict infection by DR pathogens and compared the model's diagnostic accuracy with that of current HCAP criteria. RESULTS: DR pathogens were observed in 227/580 patients (39.1%). Of 269 HCAP patients, 153 (56.9%) were infected with DR pathogens. Overtreatment was more common in HCAP than in community-acquired pneumonia (58.7% vs. 41.2%, P < 0.001). Recent hospitalisation, admission from a long-term care facility, recent antibiotic treatment and tube feeding were independently associated with DR pathogens. For pathogen prediction, the risk-scoring model showed better diagnostic accuracy than HCAP criteria (area under receiver operating-characteristic curve = 0.723 vs. 0.673, P < 0.001). CONCLUSION: According to current HCAP criteria, half of the HCAP patients were treated unnecessarily with broad-spectrum antibiotics. Risk scoring by stratifying risk factors could improve the identification of patients likely to be infected with DR pathogens.

Comparison of the tuberculin skin test and interferon-γ release assay for the diagnosis of latent tuberculosis infection before kidney transplantation.

PURPOSE: The evaluation of latent tuberculosis infection (LTBI) is recommended before kidney transplantation. The interferon-γ release assay has been reported to be more specific than the tuberculin skin test (TST) for detecting LTBI. We compared the TST and QuantiFERON-TB Gold In-Tube test (QFT-GIT) for the screening for LTBI and determined the agreement between the two tests in renal transplant recipients before transplantation. METHODS: Adult patients who were evaluated for renal transplantation between May 2010 and February 2012 at Severance Hospital in South Korea were prospectively enrolled. We performed TST and QFT-GIT. RESULTS: Of the 126 patients, 23 (19.3 %) had positive TST results and 53 (42.1 %) had positive QFT-GIT results. Agreement between the TST and QFT-GIT was fair (κ = 0.26, P < 0.001). The induration size of TST was significantly correlated with a positive rate of QFT-GIT (P = 0.015). Age (odds ratio [OR] 1.08, 95 % confidence interval [CI] 1.03-1.13, P = 0.003), male sex (OR 2.73, 95 % CI 1.17-6.38, P = 0.021), and risk for LTBI (OR 4.62, 95 % CI 1.15-18.64, P = 0.031) were significantly associated with positive QFT-GIT results. For positive TST results, only male sex was associated (OR 4.29, 95 % CI 1.40-13.20, P = 0.011). CONCLUSION: The positivity for QFT-GIT was higher than the positivity for TST, and QFT-GIT more accurately reflected the risk for LTBI. However, a further longitudinal study is needed in order to confirm that the QFT-GIT test can truly predict the development of TB after renal transplantation.

Conversion rates of an interferon-γ release assay and the tuberculin skin test in the serial monitoring of healthcare workers.

PURPOSE: Regular monitoring of latent tuberculosis (TB) infection in healthcare workers (HCWs) is recommended, but the view about the effective method and performance of serial monitoring is controversial. The aim of this study was to determine differences in conversion rates according to TB exposure risk using the tuberculin skin test (TST) and the QuantiFERON-TB Gold In-Tube (QFT-GIT), and to evaluate the reproducibility and within-subject variability of the QFT-GIT in South Korea. METHODS: Fifty-three HCWs were grouped according to their risk for TB exposure: group 1, high risk (n = 21); group 2, low risk (n = 32). Baseline and follow-up TSTs and QFT-GITs were performed from June 2009 to July 2011. Enzyme-linked immunosorbent assays (ELISAs) were repeated for the second QFT-GIT and a third QFT-GIT was performed after 8 weeks when discordant results of the second TST and QFT-GIT or a conversion or reversion were observed. RESULTS: No difference in the QFT-GIT conversion rate was evident between the two groups (15.4 vs. 6.5 %, p = 0.57), and no TST conversion was observed. The rate of QFT-GIT positivity was higher in the high-risk group (first QFT-GIT: 38.1 vs. 3.1 %, p = 0.002; second QFT-GIT: 33.3 vs. 9.4 %, p = 0.039). The re-test reproducibility of QFT-GIT results was high (100 %), and the within-subject results of repetitive QFT-GITs were variable. CONCLUSIONS: Stricter prevention strategies remain necessary in HCWs at high risk of TB exposure, and serial interferon-γ release assays (IGRAs) should be interpreted with caution in HCWs.

The responses of multiple cytokines following incubation of whole blood from TB patients, latently infected individuals and controls with the TB antigens ESAT-6, CFP-10 and TB7.7.

The development of clinically relevant biomarkers is important for diagnosing latent tuberculosis infection (LTBI) and active tuberculosis (TB) and predicting their prognoses. This study examined whether the responses of multiple cytokines can be used as a biomarker to distinguish the TB infection status and mycobacterial load. We analysed the responses of multiple cytokines (IFN-γ, IL-2, IL-10, IL-13, IL-17 and TNF-α) in the supernatant from the QuantiFERON-TB Gold In-Tube assay following stimulation of whole blood from the TB group (n = 32), LTBI group (n = 19) and healthy controls (n = 30) with TB antigens (ESAT-6, CFP-10 and TB7.7). The median responses of IFN-γ, IL-2, IL-10 and IL-13 were higher in the LTBI and active TB groups than in the non-TB control group (IFN-γ, P < 0.001; IL-2, P < 0.001; IL-10, P = 0.012; IL-13, P < 0.001). The median IL-2/IFN-γ ratio of the LTBI group was higher than that of the active TB group (P = 0.014) and differed significantly between patients with LTBI, patients with smear-negative TB and patients with smear-positive TB (P = 0.027). This difference was especially evident between the patients with LTBI and patients with smear-positive TB (P = 0.047). In conclusion, IFN-γ, IL-2, IL-10 and IL-13 can serve as biomarkers for distinguishing TB infection. In addition, the IL-2/IFN-γ ratio appears to be a biomarker for diagnosing LTBI and may be useful as a prognostic factor and for evaluating treatment responses.

Chronic obstructive pulmonary disease and metabolic syndrome: a nationwide survey in Korea.

SETTING: Systemic inflammation has been suggested to be involved in the pathogenesis of chronic obstructive pulmonary disease (COPD) and metabolic syndrome. However, the association between these two conditions is not fully understood. OBJECTIVE: To evaluate the relationship between COPD and metabolic syndrome. DESIGN: Among subjects aged ≥40 years from the 2001 Korean National Health and Nutrition Examination Survey, 1215 subjects with two or more acceptable spirometry measurements and complete anthropometric/laboratory examinations were analysed. RESULTS: A total of 133 subjects (11%, 100 men and 33 women) were newly diagnosed with COPD (forced expiratory volume in 1 second/forced vital capacity ≤ 70%). The prevalence of metabolic syndrome, based on the National Cholesterol Education Program Adult Treatment Panel III, was significantly higher in COPD subjects compared with non-COPD subjects in both sexes (33.0% vs. 22.2% in men and 48.5% vs. 29.6% in women). In men, the risk of COPD was higher in subjects with metabolic syndrome than in those without (OR 2.03, 95%CI 1.08-3.80), after adjusting for potential confounders. There was a borderline significant association between COPD and abdominal obesity among the individual component of metabolic syndrome (OR 1.95, 95%CI 0.93-4.11). CONCLUSION: In the Republic of Korea, metabolic syndrome was associated with COPD in men.

Pre-transplant risk factors for tuberculosis after kidney transplant in an intermediate burden area.

OBJECTIVE: To examine pre-transplant risk factors for the development of post-kidney transplant tuberculosis (TB) in an intermediate TB burden country, as this is important for early detection and prophylaxis to prevent post-transplant TB. DESIGN: A retrospective, longitudinal cohort study of 1097 kidney transplant patients was performed at the Severance Hospital, Seoul, South Korea, between January 2000 and March 2010. The standardised incidence ratio (SIR) of post-transplant TB compared to the general population was calculated and pre-transplant risk factors were analysed. RESULTS: Among the 1097 kidney transplant patients, 2.1% (23/1097) developed post-transplant TB, with an incidence of 445.2 cases per 100,000 patients per year. The SIR of TB in kidney transplant patients compared with the general population was 4.26 (95%CI 2.6-6.45). A positive tuberculin skin test (TST; RR 3.54, 95%CI 1.13-11.11, P = 0.03) and previously healed TB on chest radiograph (CXR; RR 8.71, 95%CI 1.00-75.84, P = 0.05) were significant pre-transplant risk factors for post-transplant TB on multivariate analysis. CONCLUSION: The incidence of TB in kidney transplant patients was higher than in the general population. Positive TST results and previously healed TB lesions visible on pre-transplant CXR were significant pre-transplant risk factors for post-kidney transplant TB.

Feasibility of hypomethylating agents followed by allogeneic hematopoietic cell transplantation in patients with myelodysplastic syndrome.

The role of hypomethylating agent therapy (HMT) as a bridge to allogeneic hematopoietic cell transplantation (alloHCT) in patients with myelodysplastic syndrome (MDS) remains undetermined. We investigated the feasibility of HMT followed by alloHCT in patients with MDS. In all, 19 patients who received HMT followed by alloHCT were analyzed. A total of 7 patients were classified as low-risk and 12 as high-risk, based on World Health Organization (WHO) classification at the time of HMT. HMT consisted of decitabine in 9 patients and azacitidine in 10. After HMT, two patients achieved CR, six mCR, three hematologic improvement alone, and six SD in terms of best response. HMT did not alter WHO classification in 15 patients (79%), whereas 1 patient (5%) improved and 3 (16%) progressed to AML. Most patients (95%) received a non-myeloablative conditioning regimen based on fludarabine/BU/anti-thymocyte globulin, and peripheral blood-mobilized stem cells. Neutrophil and platelet engraftments were achieved in 95 and 79% of patients, respectively. The incidences of acute and chronic GVHD were 42 and 26%, respectively. In all, 2-year OS rates were 68%, and the overall outcomes of those who achieved CR/mCR with HMT tended to be superior to those without CR/mCR. HMT followed by alloHCT was a feasible and effective treatment strategy for patients with MDS.