Hypersensitivity reactions to multiple anti-tuberculosis drugs.

OBJECTIVE: This study aimed to evaluate hypersensitivity reactions to anti-tuberculosis (TB) drugs. METHODS: We retrospectively compared the clinical manifestations and treatment outcomes of single and multiple drug hypersensitivity reactions (DHRs). RESULTS: Twenty-eight patients were diagnosed with anti-TB DHRs using oral drug provocation tests. Of these 28 patients, 17 patients (60.7%) had DHRs to a single drug and 11 (39.3%) had multiple DHRs. The median age of patients was 57.5 years (interquartile range [IQR], 39.2-73.2). Of the total patients, 18 patients (64.3%) were men. The median number of anti-TB drugs causing multiple DHRs was 2.0 (IQR 2.0-3.0). Rifampin was the most common drug that caused DHRs in both the single and multiple DHR groups (n = 8 [47.1%] and n = 9 [52.9%], respectively). The treatment success rate was lower in the multiple DHR group than in the single DHR group; however, the difference was not statistically significant (81.8% vs. 94.1%; P = 0.543). CONCLUSIONS: Multiple anti-TB DHRs were common in all patients who experienced DHRs, and rifampin was the most common causative drug. The treatment outcomes appeared to be poorer in patients with multiple DHRs than in those with single DHRs.

Feasibility of re-biopsy and EGFR mutation analysis in patients with non-small cell lung cancer.

BACKGROUND: In cases of EGFR-tyrosine kinase inhibitor (TKI) failure, re-biopsy may be useful to understand resistance mechanisms and guide further treatment decisions. However, performing re-biopsy is challenging because of several hurdles. We assessed the feasibility of re-biopsy in advanced non-small cell lung cancer (NSCLC) patients in real-world clinical practice. METHODS: We retrospectively reviewed the clinical and pathologic data of advanced NSCLC patients who experienced disease progression after previous treatment with EGFR-TKIs at a single tertiary hospital in Korea between January 2014 and December 2016. Re-biopsy specimens included small biopsy, surgical tissue, or liquid-based cytology. EGFR mutation was tested using peptide nucleic acid-mediated clamping PCR. RESULTS: Of the 230 NSCLC patients that experienced progression after EGFR-TKI therapy, 105 (45.7%) underwent re-biopsy. Re-biopsy was successfully performed in 94 (89.5%) patients, and 11 patients were diagnosed with no malignancy. The complication rate was 8.6%, including seven cases of pneumothorax. EGFR mutation testing was performed on 75 patients using re-biopsy specimens. Of the 57 patients who had sensitizing mutations at diagnosis, T790M mutations were found in 19 (33.3%), while 38 (66.7%) had no T790M mutation. Multivariate analysis showed that the re-biopsy group was younger (P = 0.002) and exhibited a previous response to EGFR-TKIs (P < 0.001). CONCLUSION: Re-biopsy in advanced NSCLC is feasible in real world clinical practice, particularly in younger patients and those who achieved a previous response to EGFR-TKIs.

Impact of diabetes mellitus on indeterminate results of the QuantiFERON TB Gold In-Tube test: A propensity score matching analysis.

BACKGROUND: The sensitivity of interferon-gamma release assays (IGRAs) in the detection of Mycobacterium tuberculosis infection could be affected by conditions of immune dysregulation. For this reason, diabetes mellitus (DM) may increase the frequency of indeterminate results of IGRAs. However, there have been inconsistent reports of role of DM on indeterminate IGRA results. METHODS: We retrospectively reviewed all patients who underwent QuantiFERON-TB Gold In-Tube testing (QFT-GIT) at Chonnam National University Hospital. We collected the clinical and laboratory data of these patients. RESULTS: Of all 3,391 subjects, 1,265 (37.3%) had a positive QFT-GIT result, 266 (7.8%) had an indeterminate result, and 1,860 (54.9%) had a negative result. The mean age was 54.8 ± 18.1 years and 55.0% of the patients were male. There were 512 (15.1%) patients with DM. Multivariable analysis revealed that systemic corticosteroid use, tuberculosis, lymphocytopenia, low serum albumin, and high serum C-reactive protein (CRP) levels were significantly associated with indeterminate QFT-GIT results. However, DM was not associated with indeterminate QFT-GIT results (adjusted odds ratio, 0.98; 95% confidence interval, 0.69-1.41; P = 0.939). After propensity score matching, DM was not associated with indeterminate results of QFT-GIT. CONCLUSION: In this large cohort study, DM does not affect the incidence of indeterminate results of QFT-GIT.

Clinical factors associated with weaning failure in patients requiring prolonged mechanical ventilation.

BACKGROUND: For patients requiring prolonged mechanical ventilation (PMV), weaning is difficult and mortality is very high. PMV has been defined recently, by consensus, as constituting ≥21 consecutive days of mechanical ventilation (MV) for ≥6 hours per day. This study aimed to evaluate the clinical factors predicting weaning failure in patients undergoing PMV in medical intensive care unit (ICU). METHODS: We retrospectively reviewed the clinical and laboratory characteristics of 127 patients who received MV for more than 21 days in the medical ICU at Chonnam National University Hospital in South Korea between January 2005 and December 2014. Patients who underwent surgery or experienced trauma were excluded from this study. RESULTS: Among the 127 patients requiring PMV, 41 (32.3%) were successfully weaned from MV. The median age of the weaning failure group was higher than that of the weaning success group (74.0 vs. 70.0 years; P=0.003). The proportion of male patients was 58.5% in the weaning success group and 72.1% in the weaning failure group, respectively. The most common reasons for ICU admission were respiratory causes (66.1%) followed by cardiovascular causes (16.5%) in both groups. ICU mortality and in-hospital mortality rates were 55.1% and 55.9%, respectively. In the multivariate analysis, respiratory causes of ICU admission [odds ratio (OR), 3.98; 95% confidence interval (CI), 1.29-12.30; P=0.016] and a high sequential organ failure assessment (SOFA) score on day 21 of MV (OR, 1.47; 95% CI, 1.17-1.85; P=0.001) were significantly associated with weaning failure in patients requiring PMV. The area under the receiver operating characteristic (ROC) curve of the SOFA score on day 21 of MV for predicting weaning failure was 0.77 (95% CI, 0.67-0.87; P=0.000). CONCLUSIONS: Respiratory causes of ICU admission and a high SOFA score on day 21 of MV could be predictive of weaning failure in patients requiring PMV.

Acute respiratory distress syndrome and chemical burns after exposure to chlorine-containing bleach: a case report.

Chlorine-containing bleach can cause acute respiratory distress syndrome (ARDS) and chemical burns. However, simultaneous occurrence of the two conditions caused by this agent is very rare. We describe the case of a 74-year-old female who presented with shortness of breath and hemoptysis following accidental exposure to chlorine-containing bleach. She had second- to third-degree chemical burns on both buttocks and thighs, and received mechanical ventilation because of the development of ARDS. Mechanical ventilation was discontinued on day 6 of hospitalization because of the rapid improvement of hypoxemia, and the patient was transferred to another hospital for further management of the chemical burns on day 18.

Risk of bladder cancer among patients with diabetes treated with a 15 mg pioglitazone dose in Korea: a multi-center retrospective cohort study.

It has not yet been determined whether chronic exposure to relatively low doses of pioglitazone increases risk of bladder cancer. We aimed to assess the risk of bladder cancer associated with pioglitazone in Korean patients. This was a retrospective cohort study of diabetic patients who had ≥ 2 clinic visits between November 2005 and June 2011 at one of four tertiary referral hospitals in Korea. A prevalent case-control analysis nested within the cohort was conducted to further adjust confounders. A total of 101,953 control patients and 11,240 pioglitazone-treated patients were included, in which there were 237 and 30 cases of incidental bladder cancer (64.9 and 54.9 per 100,000 person-years; age, sex-adjusted HR 1.135, 95% confidence interval [CI] 0.769-1.677), respectively. In the prevalent case-control analysis nested within the cohort, use of pioglitazone for a duration of > 6 months, but not ever use of pioglitazone, was associated with an increased rate of bladder cancer as compared to never use of pioglitazone. In conclusion, we failed to exclude the possible association between use of pioglitazone for a duration of > 6 months and bladder cancer.

Predictive clinical parameters and glycemic efficacy of vildagliptin treatment in korean subjects with type 2 diabetes.

BACKGROUND: The aims of this study are to investigate the glycemic efficacy and predictive parameters of vildagliptin therapy in Korean subjects with type 2 diabetes. METHODS: In this retrospective study, we retrieved data for subjects who were on twice-daily 50 mg vildagliptin for at least 6 months, and classified the subjects into five treatment groups. In three of the groups, we added vildagliptin to their existing medication regimen; in the other two groups, we replaced one of their existing medications with vildagliptin. We then analyzed the changes in glucose parameters and clinical characteristics. RESULTS: Ultimately, 327 subjects were analyzed in this study. Vildagliptin significantly improved hemoglobin A1c (HbA1c) levels over 6 months. The changes in HbA1c levels (ΔHbA1c) at month 6 were -2.24% (P=0.000), -0.77% (P=0.000), -0.80% (P=0.001), -0.61% (P=0.000), and -0.34% (P=0.025) for groups 1, 2, 3, 4, and 5, respectively, with significance. We also found significant decrements in fasting plasma glucose levels in groups 1, 2, 3, and 4 (P<0.05). Of the variables, initial HbA1c levels (P=0.032) and history of sulfonylurea use (P=0.026) were independently associated with responsiveness to vildagliptin treatment. CONCLUSION: Vildagliptin was effective when it was used in subjects with poor glycemic control. It controlled fasting plasma glucose levels as well as sulfonylurea treatment in Korean type 2 diabetic subjects.

Pattern of Stress-Induced Hyperglycemia according to Type of Diabetes: A Predator Stress Model.

BACKGROUND: We aimed to quantify stress-induced hyperglycemia and differentiate the glucose response between normal animals and those with diabetes. We also examined the pattern in glucose fluctuation induced by stress according to type of diabetes. METHODS: To load psychological stress on animal models, we used a predator stress model by exposing rats to a cat for 60 minutes and measured glucose level from the beginning to the end of the test to monitor glucose fluctuation. We induced type 1 diabetes model (T1D) for ten Sprague-Dawley rats using streptozotocin and used five Otsuka Long-Evans Tokushima Fatty rats as obese type 2 diabetes model (OT2D) and 10 Goto-Kakizaki rats as nonobese type 2 diabetes model (NOT2D). We performed the stress loading test in both the normal and diabetic states and compared patterns of glucose fluctuation among the three models. We classified the pattern of glucose fluctuation into A, B, and C types according to speed of change in glucose level. RESULTS: Increase in glucose, total amount of hyperglycemic exposure, time of stress-induced hyperglycemia, and speed of glucose increase were significantly increased in all models compared to the normal state. While the early increase in glucose after exposure to stress was higher in T1D and NOT2D, it was slower in OT2D. The rate of speed of the decrease in glucose level was highest in NOT2D and lowest in OT2D. CONCLUSION: The diabetic state was more vulnerable to stress compared to the normal state in all models, and the pattern of glucose fluctuation differed among the three types of diabetes. The study provides basic evidence for stress-induced hyperglycemia patterns and characteristics used for the management of diabetes patients.

Effects of a 6-Month Exenatide Therapy on HbA1c and Weight in Korean Patients with Type 2 Diabetes: A Retrospective Cohort Study.

BACKGROUND: While many studies have shown the good efficacy and safety of exenatide in patients with diabetes, limited information is available about exenatide in clinical practice in Korean populations. Therefore, this retrospective cohort study was designed to analyze the effects of exenatide on blood glucose level and body weight in Korean patients with type 2 diabetes mellitus. METHODS: We reviewed the records of the patients with diabetes who visited Seoul St. Mary's Hospital and for whom exenatide was prescribed from June 2009 to October 2011. After excluding subjects based on their race/ethnicity, medical history, whether or not they changed more than 2 kinds of oral hypoglycemic agents with exenatide treatment, loss to follow-up, or whether they stopped exenatide therapy within 6 months, a total of 52 subjects were included in the final analysis. RESULTS: The mean glycated hemoglobin (HbA1c) level and weight remarkably decreased from 8.5±1.7% to 6.7±1.0% (P<0.001) and from 82.3±15.8 kg to 78.6±16.3 kg (P<0.001), respectively. The multiple regression analysis indicated that the reduction in HbA1c level was significantly associated with a shorter duration of diabetes, a higher baseline HbA1c level, and greater weight reduction, whereas weight loss had no significant correlation with other factors. No severe adverse events were observed. CONCLUSION: These results suggest that a 6-month exenatide injection therapy significantly improved patients' HbA1c levels and body weights without causing serious adverse effects in Korean patients with type 2 diabetes.

Continuous glucose monitoring: current clinical use.

Four kinds of subcutaneous continuous glucose monitoring (CGM) machines have been currently introduced in clinical practice. These machines exhibit real-time glucose on the monitor every 5 minutes and have alarms to indicate hypoglycaemia and hyperglycaemia. However, thus far, there is no clear consensus about the clinical indications for CGM in actual clinical practice. CGM should be an ideal and powerful tool for monitoring glucose variability. Glycaemic variability has become a major concern over the years with growing evidence on its detrimental impact with respect to the risk of diabetic complications. Although the HbA1c level is ubiquitously measures in clinical practice, this level does not adequately represent glycaemic variability. Currently available evidence indicates that CGM aids in lowering the HbA1c level without increasing the incidence of severe hypoglycaemic episodes in patients with type 1 diabetes. Thus far, CGM has not been indicated for preventing severe hypoglycaemia or for treating type 2 diabetes because sufficient supporting evidence has not been obtained. Promising results have been obtained for the use of CGM for pregnant women with diabetes and for patients with hospital hyperglycaemia. Predictions regarding the feasibility of the closed-loop system have proven to be optimistic. CGM-integrated communication systems using information technology such as smart phone help controlling blood glucose more easily and effectively.

Prognostic value of 9mTc-HL91 SPECT hypoxia imaging in patients with advanced NSCLC / 中华肿瘤杂志

<p><b>OBJECTIVE</b>Tumor hypoxia can influence response to radiotherapy and other treatment modalities. Oxygenation status is proved to be an independent prognostic factor. 99mTc-HL91 (99mTc labeled 4,9-diaza-3,3,10,10-tetramethyldodecan-2,11-dione dioxime) is a potential noninvasive marker of tumor hypoxia. It has been reported that 99mTc-HL91 has certain validity for hypoxia imaging. But its clinical study had not been reported widely. This study was carried out to evaluate the relationship between the T/N ratio of HL91 SPECT hypoxia imaging and the radiotherapeutic outcome.</p><p><b>METHODS</b>32 patients with pathologically proven non-small cell lung cancer received three-dimensional conformal radiotherapy were enrolled into the study. 99mTc-HL91 SPECT scanning was performed in all patients at one or two days before radiotherapy. It was also performed in 18 patients at one or two days after the onset of radiotherapy, when they received a dose of 30 - 40 Gy already. Anterior, posterior and lateral planar images were collected at 2, 4 and 6 hours, respectively, after intravenous injection of approximately 740 MBq 99mTc-HL91. Regions of interest (ROIs) were drawn in the tumor and the contralateral normal lung tissue, and the radioactivity ratio of tumor to normal tissue (T/N) was calculated. To assess whether the tumor uptake of 99mTc-HL91 is predictive of treatment response, the SPECT results were correlated with the results of clinical follow-up.</p><p><b>RESULTS</b>The relationship between T/N ratios at 4 h images after injection was shown to be the best of three acquired images before radiotherapy. The response and overall survival to radiotherapy were analyzed for all 32 patients. The results of 9mTc-HL91 correlated well with radiotherapy response (P = 0. 002) and also patients' survival (P = 0.043). The average T/N values of 18 patients who received serial scanning were 1.57 +/- 0.18, 1.44 +/- 0.19 and 1.30 +/- 0.14, respectively. There was a significant difference between those three groups (P = 0. 000). The T/N changes during radiotherapy were not associated with the treatment outcome.</p><p><b>CONCLUSION</b>HL91 SPECT imaging can identify the hypoxia status and changes during radiotherapy in lung cancer. Hypoxia SPECT imaging with HL91 before treatment may predict radiotherapy response and patients' survival. Longer follow up in more patients is planned to confirm this result.</p>

Non-small cell lung cancer evaluated by first pass dynamic contrast-enhanced 16-slice spiral CT: correlation of tumor vascularity with pathological characteristics / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the role of first pass dynamic 16-slice spiral computed tomography in the evaluation of tumor angiogenesis in patients with non-small cell lung cancer (NSCLC) and to assess its importance in predicting pathologic characteristics.</p><p><b>METHODS</b>The first pass dynamic 16-slice spiral computed tomography was performed in 33 patients with NSCLC. Their peak heights (PH) were measured with dynamic evaluation software. Their angiogenesis were labelled by anti-CD34 monoclonal antibody. The first pass peak heights (PH) in 33 patients with NSCLC were compared with their microvessel densities (MVD) and their relationships were assessed by linear regression analysis.</p><p><b>RESULTS</b>Among the 33 patients with NSCLCs, the mean first pass PH and MVD of N1-2 were significantly higher than those at stage No (P < 0.01). The first pass PH of 33 NSCLC was correlated positively with MVDs. To differentiate stage N0 from stage N1-2 with 12 HU cutoff value of the first pass PH, the sensitivity, specificity, accuracy, positive predictive value and negative predictive value were 88.0%, 75.0%, 84.8%, 91.7% and 66.7%, respectively.</p><p><b>CONCLUSION</b>The first pass dynamic contrast enhanced CT may be a predictor of tumor angiogenesis in patients with NSCLC and its pathologic characteristics, and may be helpful to improve the accuracy of lymph node staging with conventional CT.</p>