Effectiveness of next-generation sequencing for patients with advanced non-small-cell lung cancer: a population-based registry study.

BACKGROUND: Despite the growing use of next-generation sequencing (NGS) in the management of advanced non-small-cell lung cancer (NSCLC), there is little evidence that its use leads to improved clinical outcomes. This study aimed to compare the effectiveness of NGS with that of single-gene testing (SGT) alone in patients with advanced NSCLC. MATERIALS AND METHODS: This was a retrospective cohort study conducted on patients diagnosed with advanced lung adenocarcinoma between 2017 and 2018 from a nationwide, population-based database. We identified patients who had SGT exclusively (SGT group) or underwent upfront NGS or NGS following SGT as an initial evaluation (NGS group). Patients were followed up until death or the end of the study (31 December 2019). The adjusted hazard ratio (aHR) for death was estimated using the Cox proportional hazards model. The factors affecting the adoption of NGS were identified. RESULTS: Of 8566 patients diagnosed with advanced lung adenocarcinoma, 402 and 6932 patients were assigned to the NGS and SGT groups, respectively. More NGS was carried out in younger patients, those with higher incomes, and those living in urban areas. After balancing these confounders through matching, no difference was observed in the median overall survival and risk of death between the NGS and SGT groups [18.5 versus 19.7 months, log-rank P = 0.783; aHR 0.98, 95% confidence interval (CI) 0.84-1.14, respectively]. Only in a subgroup for whom epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) inhibitors were not indicated, NGS was associated with better survival outcomes (14.1 versus 9.0 months, log-rank P = 0.006; aHR 0.82, 95% CI 0.69-0.97). CONCLUSIONS: In the real world, NGS for all-comers in patients with advanced NSCLC did not increase survival outcomes. When health care resources to support equal access to NGS are limited, upfront SGT followed by NGS may be a more efficient strategy.

Colloid coload versus crystalloid coload to prevent maternal hypotension in women receiving prophylactic phenylephrine infusion during caesarean delivery: a randomised controlled trial.

BACKGROUND: The optimal fluid strategy to prevent maternal hypotension during caesarean delivery remains unclear. This study aim was to compare the incidence of post-spinal anaesthesia hypotension in women receiving either colloid or crystalloid coload in the setting of prophylactic phenylephrine infusion during caesarean delivery. METHODS: Healthy mothers undergoing elective caesarean delivery under spinal anaesthesia were randomised to receive a rapid intravenous coload with 6% hydroxyethyl starch 130/0.4 10 mL/kg (colloid group) or balanced crystalloid solution (Plasma Solution A) 10 mL/kg (crystalloid group) during spinal anaesthesia. All women had a prophylactic phenylephrine infusion initiated at 25 µg/min immediately after the subarachnoid block and titrated to systolic blood pressure using a standardised protocol. The primary outcome was the incidence of hypotension (systolic blood pressure <80% of baseline) until delivery. RESULTS: The incidence of hypotension was 50% in the colloid group and 62% in the crystalloid group (absolute difference, -12% [95% CI -33% to 9%]; relative risk, 0.8 [95% CI 0.56 to 1.14]; P=0.314). No significant difference between groups was found in the number of hypotensive episodes (median 0.5 [IQR 0 to 1] vs 1 [0 to 2], P=0.132) or phenylephrine dose (675 [IQR 425 to 975] µg vs 750 [625 to 950] µg, P=0.109). The incidence of severe hypotension, symptomatic hypotension, bradycardia, nausea, and the neonatal outcomes were not significantly different. CONCLUSIONS: This study found no benefit of colloid coload compared with crystalloid coload for preventing maternal hypotension in the presence of prophylactic phenylephrine infusion during caesarean delivery.

Safety and Efficacy of Stent-Assisted Coiling of Unruptured Intracranial Aneurysms Using Low-Profile Stents in Small Parent Arteries.

BACKGROUND AND PURPOSE: Stent-assisted coiling of intracranial aneurysms arising from small vessels (≤ 2.0 mm) is a common procedure. However, data regarding its treatment outcomes are scarce. This study evaluated the clinical and radiologic outcomes of stent-assisted coiling using low-profile stents for aneurysms of small parent arteries. MATERIALS AND METHODS: From November 2015 to October 2020, sixty-four patients with 66 aneurysms arising from parent arteries of ≤2.0 mm were treated with stent-assisted coiling using a Low-Profile Visualized Intraluminal Support Junior (LVIS Jr) or the Neuroform Atlas stent in a single institution. The clinical and radiologic data were retrospectively reviewed, and the risk factors for procedure-related complications were evaluated. RESULTS: The LVIS Jr and Neuroform Atlas stents were used in 22 (33.3%) and 44 (66.7%) cases, respectively. Technical success was achieved in 66 cases (100%). Immediate postprocedural aneurysm occlusion grades assessed by the Raymond-Roy occlusion classification were I (57.6%), II (19.7%), and III (22.7%), respectively. Procedure-related complications occurred in 10 cases (15.2%), with 8 thromboembolic complications (12.1%) and 2 hemorrhagic complications (3.0%). Procedure-related morbidity was 4.5% without mortality. On multivariate analysis, current smoking (odds ratio = 7.1, P = .021) had a statistically significant effect on procedure-related complications. CONCLUSIONS: Stent-assisted coiling of intracranial aneurysms with low-profile stents in small vessels (≤ 2.0 mm) had a 100% success rate and a 15.2% overall complication rate with 4.5% morbidity. Current smoking was a significant risk factor associated with procedure-related complications.

Enhanced wound healing using a 3D printed VEGF-mimicking peptide incorporated hydrogel patch in a pig model.

There is a need for effective wound healing through rapid wound closure, reduction of scar formation, and acceleration of angiogenesis. Hydrogel is widely used in tissue engineering, but it is not an ideal solution because of its low vascularization capability and poor mechanical properties. In this study, gelatin methacrylate (GelMA) was tested as a viable option with tunable physical properties. GelMA hydrogel incorporating a vascular endothelial growth factor (VEGF) mimicking peptide was successfully printed using a three-dimensional (3D) bio-printer owing to the shear-thinning properties of hydrogel inks. The 3D structure of the hydrogel patch had high porosity and water absorption properties. Furthermore, the bioactive characterization was confirmed by cell culture with mouse fibroblasts cell lines (NIH 3T3) and human umbilical vein endothelial cells. VEGF peptide, which is slowly released from hydrogel patches, can promote cell viability, proliferation, and tubular structure formation. In addition, a pig skin wound model was used to evaluate the wound-healing efficacy of GelMA-VEGF hydrogel patches; the results suggest that the GelMA-VEGF hydrogel patch can be used for wound dressing.

Severe Periodontal Disease Increases Acute Myocardial Infarction and Stroke: A 10-Year Retrospective Follow-up Study.

This study aimed to evaluate the causal association of periodontal disease with acute myocardial infarction (AMI) and stroke, after controlling for various confounders among the Korean population. A retrospective cohort study using the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) was performed during 2002 to 2015 (baseline: 2002 to 2005; follow-up: 2006 to 2015) in the Republic of Korea. A total of 298,128 participants with no history of AMI or stroke were followed up for 10 y. AMI and stroke were defined by a diagnosis using the International Classification of Diseases, 10th Revision (ICD-10) guideline. Periodontal condition was classified into 3 groups (healthy, moderate periodontal disease, severe periodontal disease [SPD]) using the combination of ICD codes, treatment codes in the NHIS, and recommendation of periodontal treatment by the dentists in HEALS. Various confounders, such as sociodemographic, behavioral, systemic, and oral health factors, including hypercholesterolemia, were considered. Multivariable Cox regression analysis was applied to estimate adjusted incidence rate ratio (adjusted hazard ratio [aHR]) based on person-year of periodontal condition for AMI, stroke, and nonfatal major adverse cardiovascular events (MACEs) encompassing AMI or stroke controlling for various confounders. Stratified analyses according to age group, sex, and toothbrushing frequency were also performed. After controlling for various confounders, participants with SPD compared with non-SPD participants had a higher incidence by 11% for AMI (aHR, 1.11; 95% confidence interval [CI], 1.02-1.20), by 3.5% for stroke (aHR, 1.035; 95% CI, 1.01-1.07), and by 4.1% for MACEs (aHR, 1.04; 95% CI, 1.01-1.07). The association of SPD with AMI and MACE was highly modified in females and adults aged 40 to 59 y. In the total Korean population, SPD increased total AMI events by 4.3%, total stroke events by 1.4%, and the total MACEs by 1.6%. Our data confirmed that SPD was causally associated with the new events of AMI and stroke.

Vesicular glutamate transporter-immunopositive axons that coexpress neuropeptides in the rat and human dental pulp.

AIM: To examine the type of vesicular glutamate transporter (VGLUT)-immunopositive (+) axons that coexpress neuropeptides in the rat and human dental pulp, which may help understand peripheral mechanism of pulpal inflammatory pain in rats and humans. METHODOLOGY: The trigeminal ganglia (TG) and the dental pulp of the maxillary molar teeth from three male Sprague-Dawley rats weighing 300-330 g and dental pulps of three healthy human (male) maxillary premolar teeth from three 16 to 28-year-old patients extracted for orthodontic treatment were used. The type of VGLUT + axons that coexpress substance P (SP)- and/or calcitonin gene-related peptide (CGRP) and parvalbumin in the rat TG and in the axons of the rat and the human dental pulp was examined by double fluorescence immunohistochemistry and quantitative analysis. Results were analyzed using one-way anova and the Kruskal-Wallis test. RESULTS: SP and CGRP were expressed in many human VGLUT1 + pulpal axons but not in the rat VGLUT1 + TG neurons and pulpal axons (P < 0.05). SP and CGRP were expressed in a considerable number of human VGLUT2 + pulpal axons and also in many rat TG neurons and pulpal axons. The fraction of VGLUT1 + axons expressing parvalbumin was about three times higher in the rat than in the human dental pulp (P < 0.05). CONCLUSIONS: These findings suggest that the types of VGLUT + axons, which release neuropeptides, may be different between the rat and the human dental pulp, raising a possibility that peripheral mechanism of pulpal inflammatory pain may be different between rats and humans.

Association of left ventricular hypertrophy with the level of thyroid hormone in euthyroid state.

PURPOSE: It has been demonstrated that variation in thyroid hormone levels even within normal range was associated with increased cardiovascular risk. However, available data are still insufficient on association between left ventricular hypertrophy (LVH) and thyroid hormone levels within euthyroid state. METHODS: In 69,298 Koreans with euthyroid function, we evaluated association between echocardiographically detected LVH and thyroid hormone levels within the normal range. Study participants were categorized into elderly (age ≥ 40) and younger (age < 40) groups, where subjects were divided into four groups according to quartile levels of thyroxine (FT4), triiodothyronine (FT3), and thyroid-stimulating hormone (TSH). Multivariable adjusted logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence interval (CI) for LVH (adjusted ORs [95% CI]) across quartile levels of thyroid hormones. RESULTS: In elderly group, adjusted ORs for LVH generally higher in the first quartile group than other quartile groups, despite no statistical significance in some cases (first quartile: reference, second quartile: 0.86 [0.67-1.11] in TSH, 0.75 [0.58-0.95] in FT4 and 0.63 [0.49-0.81] in FT3, third quartile: 0.70 [0.54-0.92] in TSH, 0.79 [0.61-1.02] in FT4 and 0.72 [0.55-0.93] in FT3, fourth quartile: 0.81 [0.65-1.04] in TSH, 0.85 [0.65-1.10] in FT4 and 0.58 [0.44-0.77] in FT3). This finding was similarly found in the younger group, despite discrepancy in some cases. CONCLUSION: In euthyroid state, low normal levels in FT4, FT3 and TSH were more strongly associated with LVH.

Risk factors and renal outcomes of low bone mineral density in patients with non-dialysis chronic kidney disease.

Bone disorder is a common complication of chronic kidney disease (CKD). The clinical usefulness of bone mineral density (BMD) in CKD is not well known. Our study shows that low BMD is associated with physical activity and dietary Na/K intake ratio and can predict poor renal outcome in non-dialysis CKD. PURPOSE: Despite evidence of a link between bone mineral disorders and chronic kidney disease (CKD), the clinical implications of bone mineral density (BMD) in CKD are not well established. We investigated risk factors and renal outcomes of low BMD in CKD. METHODS: We analyzed data from the KNOW-CKD. BMD measured by dual-energy x-ray absorptiometry was classified by T score: normal (T score ≥ - 1.0), osteopenia (- 1.0 > T score > - 2.5), and osteoporosis (T score ≤ - 2.5) of the lumbar spine, hip, or femoral neck. Logistic regression analysis to assess risk factors of low BMD (T score < - 1.0) and Cox proportional hazards models to estimate risk of incident end-stage renal disease (ESRD). RESULTS: Low BMD was prevalent (osteopenia 33%; osteoporosis 8%) in 2128 adults with CKD (age 54 ± 12 years; male 61%). Over a median follow-up of 4.3 years, there were 521 cases of incident ESRD. Lower BMD was associated with female sex, older age, low eGFR, low BMI, and lifestyle factors of physical activity (odds ratio (OR) = 0.62, 95% confidence interval (0.49-0.77)) and spot urine Na/K ratio (1.07 (1.00-1.15)). In adjusted Cox models, low BMD was associated with increased incident ESRD (hazard ratio (HR) = 1.14 (0.92-1.41) for osteopenia; 1.43 (1.01-2.04) for osteoporosis, P for trend < 0.05) compared with the reference of normal BMD. The association between low BMD and ESRD was similar according to T score discordance classification. CONCLUSIONS: Low BMD was associated with modifiable lifestyle factors including low physical activity and high dietary Na/K intake ratio. The presence of low BMD is associated with poor renal outcomes in non-dialysis CKD.

Semi-automatic segmentation and surface reconstruction of computed tomography images by using rotoscoping and warping techniques.

BACKGROUND: Quick and large-scale segmentation along with three-dimensional (3D) reconstruction is necessary to make precise 3D musculoskeletal models for surface anatomy education, palpation training, medical communication, morphology research, and virtual surgery simulation. However, automatic segmentation of the skin and muscles remain undeveloped. MATERIALS AND METHODS: Therefore, in this study, we developed workflows for semi-automatic segmentation and surface reconstruction, using rotoscoping and warping techniques. RESULTS: The techniques were applied to multi detector computed tomography images, which were optimised to quickly generate surface models of the skin and the anatomical structures underlying the fat tissue. CONCLUSIONS: The workflows developed in this study are expected to enable researchers to create segmented images and optimised surface models from any set of serially sectioned images quickly and conveniently. Moreover, these optimised surface models can easily be modified for further application or educational use.

Randomized, Open-Label, Phase IV, Korean Study of Kidney Transplant Patients Converting From Cyclosporine to Prolonged-Release Tacrolimus Plus Standard- or Reduced-Dose Corticosteroids.

BACKGROUND: This 24-week, multicenter, randomized, exploratory, comparative, open-label, phase-IV study assessed the safety and efficacy of prolonged-release tacrolimus (PR-T) with reduced-dose versus standard-dose corticosteroids in stable kidney transplant recipients in Korea after converting from cyclosporine-based therapy. METHODS: At baseline, patients were converted from cyclosporine-based to PR-T-based immunosuppression and randomized (1:1) to receive either corticosteroids maintained at prestudy dose (standard-dose group) or tapered from week 4 to 50% of the prestudy dose by week 12 (reduced-dose group). Patients were seen at baseline and weeks 1, 4, 12, and 24. The primary endpoint was change in estimated glomerular filtration rate (Modification-of-Diet-in-Renal-Disease-4) between baseline and week 24. Secondary endpoints included either acute rejection or patient-reported satisfaction with PR-T. Adverse events (AEs) were recorded. RESULTS: Overall, 150 patients were randomized into a reduced-dose group (n = 73) and a standard-dose group (n = 77). At week 24, mean ± standard deviation for corticosteroid dose was 2.5 ± 0.9 mg and 5.0 ± 1.3 mg, respectively. Mean change in estimated glomerular filtration rate from baseline to week 24 was +1.5 ± 9.1 mL/min/1.73 m2 (P = .1567) and +3.4 ± 10.6 mL/min/1.73 m2 (P = .0065), respectively, and not significantly different between groups. There were no acute rejection episodes. Most respondents (>70%) considered PR-T more convenient than cyclosporine. AE incidence was similar between groups. The most common AEs experienced by ≥3% of patients in either treatment group were gastrointestinal events (20.8% and 28.6% of patients receiving reduced- and standard-dose corticosteroids, respectively). Most AEs in both treatment groups were mild or moderate in severity. CONCLUSION: Renal function was maintained following conversion from cyclosporine to PR-T, irrespective of corticosteroid regimen; PR-T enables reduced corticosteroid dosage.

Comparison between general, spinal, epidural, and combined spinal-epidural anesthesia for cesarean delivery: a network meta-analysis.

BACKGROUND: This study is a network meta-analysis to compare maternal and fetal outcomes associated with four different anesthetic techniques for cesarean delivery. METHODS: An arm-based, random-effects frequentist network meta-analysis was performed. A random effect model was selected considering deviance information criteria. Randomized trials reporting the following outcomes were included: Apgar score at 1- or 5-min; umbilical arterial and venous pH; umbilical arterial pH <7.2; and neonatal score at 2-4 hours. Loop-specific heterogeneity was evaluated by risk of odds ratio and τ2. Quality of evidence was assessed using the GRADE approach. RESULTS: Data from 46 randomized trials including 3689 women contributed to the study. There were significant differences in Apgar score ≤6 at 1 min between spinal versus general anesthesia (odds ratio 0.27, 95% confidence interval [CI] 0.13 to 0.55: moderate quality evidence) and Apgar scores at 1- and 5-min, favoring spinal anesthesia. Umbilical venous pH associated with epidural anesthesia was significantly higher than that with general anesthesia (mean difference 0.010, 95% CI 0.001 to 0.020: moderate quality evidence) or spinal anesthesia. Spinal anesthesia was ranked best for Apgar score ≤6 at 1-min (SUCRA=89.8), Apgar score at 1-min (SUCRA=80.4) and 5-min (SUCRA=90.5). Epidural anesthesia was ranked highest for umbilical venous pH (SUCRA=87.4) and neonatal score (SUCRA=79.3). CONCLUSIONS: Spinal and epidural anesthesia were ranked high regarding Apgar scores and epidural anesthesia was ranked high regarding umbilical venous pH, but the results were based on small heterogeneous studies with high or unclear risks of bias.

A Case Series of Asymptomatic Hemodialysis Catheter-Related Right Atrial Thrombi That Are Incidentally Detected Prior to Kidney Transplantation.

A hemodialysis (HD) catheter-related right atrial thrombus (RAT) is rarely encountered prior to kidney transplantation (KT) but necessitates a decision about whether to anticoagulate and/or delay the surgery. There is controversy surrounding the clinical implications of a RAT in this situation. It is sometimes considered fatal but other opinions consider it to be benign, especially when incidentally detected. We reviewed the clinical characteristics, management, and outcomes of a patient series with HD catheter-related RAT detected prior to KT and speculated on its clinical significance. Among 3677 cases of KT performed on 3607 patients between January 1997 and September 2015 in our single tertiary center, 11 cases of HD catheter-related RAT detected on transthoracic echocardiography (TTE) prior to KT were included for analysis. The average maximal diameter of the RAT was 23.2 ± 16.3 (SD in mm) and 9 (81.8%) of these 11 patients had no symptoms associated with the RAT. Four patients (36.3%) had their catheters replaced, 5 patients (45.5%) had their catheters removed, and the catheters were maintained in the remaining 2 patients (18.2%). Six patients (54.5%) were anticoagulated with either heparin or warfarin. However all 11 patients had a successful KT suggesting that a HD catheter-related RAT incidentally detected prior to this surgery may not be as serious as previously considered and should not be a reason for delaying the transplantation.

Effect of prolonged inspiratory time on gas exchange during robot-assisted laparoscopic urologic surgery.

BACKGROUND: Gas exchange disturbance may develop during urologic robotic laparoscopic surgery with the patient in a steep Trendelenburg position. This study investigated whether prolonged inspiratory time could mitigate gas exchange disturbances including hypercapnia. METHODS: In this randomized cross-over trial, 32 patients scheduled for robot-assisted urologic surgery were randomized to receive an inspiratory to expiratory time ratio (I:E) of 1:1 for the first hour of pneumoperitoneum followed by 1:2 for last period of surgery (group A, n = 17) or I:E of 1:2 followed by 1:1 (group B, n = 15). Arterial blood gas analysis, airway pressure and hemodynamic variables were assessed at four time points (T1: 10 min after induction of general anesthesia, T2: 1 h after the initiation of pneumoperitoneum, T3: 1 h after T2 and T4: at skin closure). The carry over effect of initial I:E was also evaluated over the next hour through arterial blood gas analysis. RESULTS: There was a significant decrease in partial pressure of oxygen in arterial blood (PaO2) for both groups at T2 and T3 compared to T1 but in group B the PaO2 at T4 was not decreased from the baseline. Partial pressure of carbon dioxide in arterial blood (PaCO2) increased with I:E of 1:2 but did not significantly increase with I:E of 1:1; however, there were no differences in PaO2 and PaCO2 between the groups. CONCLUSION: Decreased oxygenation by pneumoperitoneum was improved and PaCO2 did not increase after 1 h of I:E of 1:1; however, the effect of equal ratio ventilation longer than 1 h remains to be determined. There was no carryover effect of the two different I:E ratios.

Pharmacological interventions for protecting renal function after cardiac surgery: a Bayesian network meta-analysis of comparative effectiveness.

Many drugs have been investigated as potentially protective of renal function after cardiac surgery. However, their comparative effectiveness has not been established. We performed an arm-based hierarchical Bayesian network meta-analysis including 95 randomised controlled trials with 28,833 participants, which allowed us to compare some agents not previously compared directly. Renal outcomes, including: the incidence of postoperative renal dysfunction and haemodialysis; serum creatinine level at 24 hours postoperatively; all-cause mortality; and length of hospital and ICU stay, were compared. Exploratory meta-regression was conducted for potential effect modifiers. A random effects model was selected according to the evaluation of model fit by deviance information criteria. Atrial natriuretic peptide (odds ratio (95%CrI) 0.28 (0.17-0.48); moderate-quality evidence), B-type natriuretic peptide, dexmedetomidine, levosimendan and N-acetyl cysteine significantly decreased the rate of postoperative renal dysfunction compared with placebo. Atrial natriuretic peptide (OR (95%CrI) 0.24 (0.10-0.58); low-quality evidence), B-type natriuretic peptide, and dexamethasone significantly decreased the need for haemodialysis. Levosimendan significantly decreased mortality, OR (95%CrI) 0.49 (0.27-0.91); low-quality evidence). The benefit of atrial natriuretic peptide was still apparent when baseline renal function was normal. None of the potential effect modifiers were significantly correlated with our renal outcomes. Atrial natriuretic peptide was ranked best regarding renal dysfunction, haemodialysis and length of hospital stay. Levosimendan was ranked best regarding mortality and ICU stay. However, our results should be interpreted cautiously given the assumptions made about transitivity and consistency.

U-shaped relationship between depression and body mass index in the Korean adults.

BACKGROUND: Although a number of studies have examined the relationship between depression and obesity, it is still insufficient to establish the specific pattern of relationship between depression and body mass index (BMI) categories. Thus, this study was aimed to investigate the relationship between depression and BMI categories. METHODS: A cross-sectional study was conducted for a cohort of 159,390 Korean based on Kangbuk Samsung Health Study (KSHS). Study participants were classified into 5 groups by Asian-specific cut-off of BMI (18.5, 23, 25 and 30kg/m2). The presence of depression was determined by Center for Epidemiologic Studies-Depression scales (CES-D)≥16 and≥25. The adjusted odd ratios (ORs) for depression were evaluated by multiple logistic regression analysis, in which independent variable was 5 categories of BMI and dependent variable was depression. Subgroup analysis was conducted by gender and age. RESULTS: When normal group was set as a reference, the adjusted ORs for depression formed U-shaped pattern of relationship with BMI categories [underweight: 1.31 (1.14-1.50), overweight: 0.94 (0.85-1.04), obese group: 1.01 (0.91-1.12), severe obese group: 1.28 (1.05-1.54)]. This pattern of relationship was more prominent in female and young age group than male and elderly subgroup. BMI level with the lowest likelihood of depression was 18.5kg/m2 to 25kg/m2 in women and 23kg/m2 to 25kg/m2 in men. CONCLUSIONS: There was a U-shaped relationship between depression and BMI categories. This finding suggests that both underweight and severe obesity are associated with the increased risk for depression.

Comparison of the characteristics of Mycobacterium tuberculosis isolates from sputum and lung lesions in chronic tuberculosis patients.

Mycobacterium tuberculosis (Mtb) in sputum originates from lung cavities in tuberculosis (TB) patients. But drug susceptibility testing (DST) of sputum Mtb can not be conducted the same as in the lung because mutagenesis of bacilli may be happening in the lung during treatment and result in the possibility of the presence of heterogeneous drug-resistant subpopulations in the different lung lesions. This could be one of the reasons for low cure rates for multi-drug resistant (MDR)-TB. We studied the resected lungs of nine surgery patients with chronic TB. The isolates isolated from the sputum and different lung lesions of each patient were tested for phenotypic DST and genotyped using restriction fragment length polymorphism (RFLP) typing method. Genetic analysis to resistance to first and second line drugs was also performed. Five of nine patients were MDR-TB and three XDR-TB. DST results for ten anti-TB drugs were in accordance among different lung lesions in eight patients. However, only three of these eight patients showed the concordance of DST with sputum. Even though the isolates were heteroresistant, genotyping them by RFLP showed the clonal population in each individual patient. Six of eight followed-up patients achieved successful cure. In conclusion, the heteroresistance between sputum and lung lesions and a clonal population without mixed infection might provide useful information in establishing treatment regimen and surgery decision for MDR- and XDR-TB.

Testosterone effects on pain and brain activation patterns.

BACKGROUND: This study investigated whether pain and pain-related unpleasantness ratings were altered by blood testosterone levels. We also investigated whether activation of brain regions that represent pain intensity [primary somatosensory cortex (S1)] and pain-related unpleasantness [perigenual ACC (pACC) and orbitofrontal cortex (OFC)] were affected by blood testosterone levels. METHODS: Twenty-six healthy men were recruited. Blood testosterone levels were measured before fMRI scanning. The participants were classified into two groups (high vs. low testosterone) according to their blood testosterone level (each group n = 13). The middle finger was immersed in a 50°C water bath (50°C, 30 s, five times) to induce identical noxious stimulation in all participants. RESULTS: The low testosterone group showed statistically significantly higher pain (P = 0.047), unpleasantness (P = 0.047), anxiety (P = 0.015), and fear ratings (P = 0.01) than the high testosterone group. Fear rating increased as pain rating rose and as testosterone level decreased (P < 0.001). When participants received noxious stimulation, the pACC and OFC were more highly activated in the low testosterone group compared to the high testosterone group. Activation of S1, a region related to pain intensity, did not differ between both groups. CONCLUSION: Compared to the high testosterone group, the low testosterone group had significant activation in the pACC and OFC, regions that represent pain-related unpleasantness, but not in S1 that represents pain intensity, leading to higher pain ratings. These findings emphasize the importance of considering the effects of testosterone levels when treating patients.

Weight loss and waist reduction is associated with improvement in gastroesophageal disease reflux symptoms: A longitudinal study of 15 295 subjects undergoing health checkups.

BACKGROUND: General obesity and abdominal obesity is an established risk factor of gastroesophageal reflux disease (GERD). However, the influence of weight or waist change on improvement of GERD is unclear. Our aim was to investigate if weight loss or waist reduction improves GERD symptoms and esophagitis. METHODS: A retrospective longitudinal study of 15 295 subjects who underwent gastroscopy for a health checkup and reported GERD symptoms between 2011 and 2013, and repeated a checkup until 2014 was conducted. The improvement of GERD symptoms and esophagitis according to weight loss (≥-2, -0.5 to -2 kg/m2 in body mass index [BMI]), waist reduction (≥-5, -0.1 to -0.5 cm) and baseline BMI/waist circumference (WC) categories was assessed using logistic regression. KEY RESULTS: Weight loss or waist reduction was associated with improvement in GERD symptoms only in subjects with general or abdominal obesity. Among subjects with general obesity (BMI ≥25 kg/m2 ) and decreased ≥2 kg/m2 in BMI, the adjusted odds ratio (OR) of improvement in GERD symptoms was 2.34 (95% confidence interval [CI] 1.70-2.83). Among subjects with abdominal obesity (WC ≥90 cm) and decreased ≥5 cm in WC, the corresponding OR was 2.16 (95% CI 1.56-2.90). There was no association between weight loss or waist reduction and improvement in esophagitis. CONCLUSIONS & INFERENCES: Weight loss or waist reduction was associated with improvement in GERD symptoms only in subjects with general or abdominal obesity. Weight loss or waist reduction will be an important treatment option in obese patients.