Trends of antibiotic use at the end-of-life of cancer and non-cancer decedents: a nationwide population-based longitudinal study (2006-2018).

Objective: This study aimed to assess the actual burden of antibiotic use among end-of-life (EOL) patients in South Korea and to compare trends between cancer and non-cancer decedents. Design: Population-based mortality follow-back study. Setting: Data from the Korean National Health Insurance Database, covering the period from January1, 2006, to December 31, 2018, provided for research by the National Health Insurance Service (NHIS), were used. Participants: All decedents from 2006 to 2018 were included and categorized as cancer decedents or non-cancer decedents. Methods: Annual antibiotic consumption rates and prescription rates were calculated, and Poisson regression was used to estimate their trends. Results: Overall antibiotic consumption rates decreased slightly among decedents in their final month with a less pronounced annual decrease rate among cancer decedents compared to non-cancer decedents (0.4% vs 2.3% per year, P <.001). Over the study period, although narrow spectrum antibiotics were used less, utilization and prescription of broad-spectrum antibiotics steadily increased, and prescription rates were higher in cancer decedents compared to non-cancer controls. Specifically, carbapenem prescription rates increased from 5.6% to 18.5%, (RR 1.087, 95% CI 1.085-1.088, P <.001) in cancer decedents and from 2.9% to 13.2% (RR 1.115, 95% CI 1.113-1.116, P <.001) in non-cancer decedents. Conclusions: Our findings show that patients at the EOL, especially those with cancer, are increasingly and highly exposed to broad-spectrum antibiotics. Measures of antibiotic stewardship are required among this population.

Differences in the risk of clinical failure between thiopurine and methotrexate in bio-naïve patients with Crohn's disease: a Korean nationwide population-based study.

Background: Although immunomodulators are widely prescribed in patients with Crohn's disease (CD), it is unclear whether there is a difference in treatment outcomes between thiopurines and methotrexate (MTX). Objective: To compare the risk of clinical failure between thiopurines and MTX in bio-naïve patients with CD. Design: Nationwide, population-based study. Methods: We used claims data from the Korean National Health Insurance Service. After inverse probability of treatment weighting, logistic regression and Cox proportional hazard analyses were used to evaluate the risk of clinical failure in bio-naïve patients with CD treated with thiopurine (thiopurine group) or MTX (MTX group). Results: Overall, 10,296 adult and pediatric patients with CD [9912 (96.3%) and 384 (3.7%) in the thiopurine and MTX groups, respectively] were included. The odds ratios (ORs) of failure to induce remission were significantly higher in the MTX group than in the thiopurine group [adjusted OR (aOR), 1.115; 95% confidence interval (CI), 1.045-1.190; p = 0.001]. However, the opposite result was observed only in patients without concomitant steroid use: the MTX group had a lower risk of induction failure than the thiopurine group (aOR, 0.740; 95% CI, 0.673-0.813; p < 0.001). The risk of overall maintenance failure was higher in the MTX group than in the thiopurine group [adjusted hazard ratio (aHR), 1.117; 95% CI, 1.047-1.191; p = 0.001]. The risk of overall maintenance failure was higher in the standard-dose MTX group than in the low-dose MTX group (aHR, 1.296; 95% CI, 1.134-1.480; p < 0.001). There was no significant difference in the risk of maintenance failure according to the administration route of MTX. Conclusion: Thiopurine is more effective than MTX in inducing and maintaining remission in bio-naïve patients with CD; however, the concomitant use of steroids influences inducing remission.

Differences in treatment efficacy between thiopurine and methotrexate in patients with Crohn's disease who were not treated with biologics Immunomodulators (IMMs) used in the treatment of Crohn's disease (CD) include medications such as thiopurine and methotrexate (MTX). Although IMMs are widely prescribed for patients with CD, it remains unclear whether treatment outcomes differ according to the specific types and dosages of IMMs and administration routes of MTX. In this study, we investigated the risk of treatment failure between thiopurines and MTX in CD patients not undergoing biologic treatment. Patients treated with MTX had a higher risk of maintenance failure than those treated with thiopurines. There was no difference in the risk of treatment failure according to the dosage of thiopurine. However, the risk of maintenance failure was higher in patients receiving standard-dose MTX than in those receiving low-dose MTX. There was no difference in the risk of maintenance failure according to the administration route of MTX. Our study enriches the knowledge regarding the treatment efficacy of thiopurines and MTX for patients with CD and may help clinicians develop appropriate treatment plans.

Effect of multimorbidity on hypertension management.

Multimorbidity, the coexistence of multiple health conditions, is associated with functional decline, disability, and mortality. We aimed to investigate the effects of multimorbidity on hypertension treatment and control rates by analyzing data from the Korean National Health and Nutrition Examination Survey database, which is a cross-sectional, nationally representative survey conducted by the Korean government. Multimorbidity, defined as having two or more chronic diseases, was evaluated by blood pressure measurements, blood chemistry examinations, and questionnaires. We classified the participants according to the number of multimorbidities from 0 to ≥ 6. Association analysis was performed to identify the patterns of multimorbidity related to hypertension control. From 2016 to 2020, 30,271 adults (≥ 20 years) were included in the analysis (age: 52.1 ± 16.8 years, male: 44.0%), and 14,278 (47.2%) had multimorbidity. The number of chronic conditions was significantly higher in older adults, women, and hypertensive patients. Multimorbidity was associated with hypertension treatment. The number of chronic conditions was significantly higher in controlled compared to uncontrolled patients (3.6 ± 1.7 vs 2.9 ± 1.6, p < 0.001). But the control rate of hypertension among treated patients was lower in patients with multimorbidity (75.6% in hypertension only group vs 71.8% in multimorbidity group, p = 0.009). Multimorbidity patterns showed distinct features in treated and controlled hypertensive patients. In conclusion, multimorbidity has a beneficial effect on the treatment of hypertension, but the control rate of systolic blood pressure was lower among the patients with multimorbidity. More attention should be paid to the hypertensive patients with multimorbidity to improve the control rate of hypertension.

Epidemiology and demographics of slipped capital femoral epiphysis in South Korea: A nationwide cohort study.

BACKGROUND: This study investigated the epidemiology and demographics of slipped capital femoral epiphysis (SCFE) in South Korea using a nationwide population-based database. METHODS: Information on sex, age at onset, endocrine comorbidities, history of growth hormone therapy, history of radiation therapy, surgical methods, and complications in patients with SCFE aged younger than 18 years between 2007 and 2019 was retrieved from the Korean Health Insurance Review and Assessment Service database. RESULTS: Data were available for 586 children (429 boys, 157 girls). The average age at onset was 11.1 ± 1.8 years (boys, 11.3 ± 1.9; girls, 10.6 ± 1.5). Five hundred and twenty-nine (90.3%) patients were aged 9-14 years; the incidence rate in this age group was 6.0/100,000 (95% confidence interval, 5.5-6.6) and significantly higher in boys (8.4 vs 3.5, p<0.001). There was a significant increase in the annual incidence rate from 0.96/100,000 in 2009 to 2.05/100,000 in 2019 (p = 0.006). Ninety-five patients (16.2%) had endocrine comorbidities or a history of hormone/radiation therapy. Osteotomy and internal fixation were performed in 59 patients and in situ pinning in 527. Seventy-six patients developed postoperative complications. CONCLUSION: The annual incidence rate of SCFE in South Korea has increased since 2009.

Negative Conversion of Polymerase Chain Reaction and Clinical Outcomes according to the SARS-CoV-2 Variant in Critically Ill Patients with COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an ongoing global public health threat and different variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been identified. This study aimed to analyse the factors associated with negative conversion of polymerase chain reaction (PCR) and prognosis in critically ill patients according to the SARS-CoV-2 variant. METHODS: This study retrospectively analysed 259 critically ill patients with COVID-19 who were admitted to the intensive care unit of a tertiary medical center between January 2020 and May 2022. The Charlson comorbidity index (CCI) was used to evaluate comorbidity, and a negative PCR test result within 2 weeks was used to define negative PCR conversion. The cases were divided into the following three variant groups, according to the documented variant of SARS-CoV-2 at the time of diagnosis: non-Delta (January 20, 2020-July 6, 2021), Delta (July 7, 2021- January 1, 2022), and Omicron (January 30, 2022-April 24, 2022). RESULTS: The mean age of the 259 patients was 67.1 years and 93 (35.9%) patients were female. Fifty (19.3%) patients were smokers, and 50 (19.3%) patients were vaccinated. The CCI (hazard ratio [HR], 1.555; p<0.001), vaccination (HR, 0.492; p=0.033), and Delta variant (HR, 2.469; p=0.002) were significant factors for in-hospital mortality. The Delta variant (odds ratio, 0.288; p=0.003) was associated with fewer negative PCR conversion; however, vaccination (p=0.163) and remdesivir (p=0.124) treatments did not. CONCLUSION: The Delta variant of SARS-CoV-2 is associated with lower survival and negative PCR conversion. Contrary to expectations, vaccination and remdesivir may not affect negative PCR conversion in critically ill patients with COVID-19.

Long-term Effects of the Eradication of Helicobacter pylori on Metabolic Parameters, Depending on Sex, in South Korea.

Background/Aims: Helicobacter pylori (HP) infection is positively associated with metabolic syndrome (MS). However, the long-term effects of eradication therapy on MS and sex differences have not been thoroughly studied. We aimed to investigate the long-term effects of HP eradication on MS and sex differences. Methods: This study included 2,267 subjects who visited a tertiary referral center between May 2003 and May 2019. HP was diagnosed by histology, a Campylobacter-like organism test, and culture, and the subjects were prospectively followed up. The participants were categorized into three groups: HP uninfected, HP infected but non-eradicated, and HP eradicated. The baseline characteristics and changes in metabolic parameters after HP eradication were compared over a 5-year follow-up period. Results: Among 1,521 subjects, there was no difference in baseline metabolic parameters between the HP-uninfected (n=509) and HP-infected (n=1,012) groups, regardless of sex. Analysis of the metabolic parameters during follow-up among HP-uninfected (n=509), HP-non-eradicated (n=346), and HP-eradicated (n=666) groups showed that high-density lipoprotein (HDL) and the body mass index (BMI) increased after eradication, with a significant difference at 1-year of follow-up. In females, HDL increased after eradication (p=0.023), and the BMI increased after eradication in male subjects (p=0.010). After propensity score matching, the HDL change in female remained significant, but the statistical significance of the change in BMI in the male group became marginally significant (p=0.089). Conclusions: HP eradication affected metabolic parameters differently depending on sex. HDL significantly increased only in females over time, especially at 1-year of follow-up. In contrast, BMI showed an increasing tendency over time in males, especially at the 1-year follow-up.

Efficacy and safety of daily home-based transcranial direct current stimulation as adjunct treatment for bipolar depressive episodes: Double-blind sham-controlled randomized clinical trial.

Background: Although transcranial direct current stimulation (tDCS) is known to be a promising therapeutic modality for unipolar depression, the efficacy and safety of tDCS for bipolar depressive episodes (BD) are still unknown and clinical trials of home-based tDCS treatment are scarce. As a result, we set out to investigate the efficacy and safety of home-based tDCS for the treatment BD. Methods: Participants (n = 64), diagnosed as bipolar disorder as per the diagnostic and statistical manual of mental disorders (DSM-5), were randomly assigned to receive tDCS. Hamilton Depression Rating Scale (HDRS-17) scores were measured at the baseline, week 2, 4, and 6, and home-based tDCS (for 30 min with 2 mA) was self-administered daily. Results: Of the 64 patients (15.6% bipolar disorder I, 84.4% bipolar disorder II), 41 patients completed the entire assessment. In the intention-to-treat analysis, time-group interaction for the HDRS-17 [F (3, 146.36) = 2.060; p = 0.108] and adverse effect differences between two groups were not statistically significant, except the pain score, which was higher in the active group than the sham group (week 0-2: p < 0.01, week 2-4: p < 0.05, and week 4-6: p < 0.01). Conclusion: Even though we found no evidence for the efficacy of home-based tDCS for patients with BD, this tool was found to be a safe and tolerable treatment modality for BD. Clinical trial registration: [https://clinicaltrials.gov/show/NCT03974815], identifier [NCT03974815].

Effect of valproate and lithium on dementia onset risk in bipolar disorder patients.

Although valproate and lithium are most commonly prescribed for bipolar disorder patients, studies comparing their effects on the risk of dementia are limited. Choosing a safer mood stabilizer is clinically crucial as elderly bipolar disorder patients are at high risk of dementia onset. Therefore, we aim to evaluate and compare the effects of valproate and lithium on the risk of dementia in elderly bipolar disorder patients. This study involved 4784 bipolar disorder patients aged 50 years or older from the Korean Health Insurance Review and Assessment Service database. We estimated the risk of dementia in valproate-only users, lithium-only users, and both users compared to both medication non-users using multivariable Cox proportional hazard models. Compared to non-users, valproate-only users and both users showed a higher risk of dementia (59% and 62%, respectively). In sub-group analysis, valproate increased the dementia risk when prescribed for at least 59 days or 23 cumulative defined daily doses. However, the dementia risk associated with lithium is unclear. Therefore, we concluded that lithium has the potential to be the safer choice as a mood stabilizer over valproate for elderly bipolar disorder patients considering the risk of dementia.

Postoperative Hormone Replacement Therapy and Survival in Women with Ovarian Cancer.

The effect of postoperative hormone replacement therapy (HRT) on survival in women with ovarian cancer remains unclear. This study aimed to investigate the impact of postoperative HRT on survival in women with ovarian cancer using the nationwide cohort study. Women aged ≤60 and diagnosed with ovarian cancer that received primary surgery were followed-up for 5.6 ± 2.9 years. Mean ages of women administered HRT (the HRT group; n = 263) or not administered HRT (the control group; n = 1521) were 41.5 ± 8.5 and 41.0 ± 11.4 years, respectively. After adjustment for covariables, OS was significantly greater in the HRT group (HR 0.618; 95% CI 0.414−0.922; p = 0.018). Kaplan−Meier curve analysis showed OS was significantly higher in the HRT group (85.3% vs. 76.6%; p = 0.016). The ratio of women with HRT to women without HRT increased significantly with time (restricted mean survival times for OS, p < 0.001). In addition, OS was significantly greater for those that received HRT for >5 years than for those that received HRT for ≤0.5 years (HR 0.234; 95% CI 0.059−0.936; p = 0.040). Postoperative HRT improved survival among women with ovarian cancer. The impact of HRT on survival increased with time and treatment duration.

Evaluation of Patients' Adverse Events During Contact Isolation for Vancomycin-Resistant Enterococci Using a Matched Cohort Study With Propensity Score.

Importance: Although contact isolation has been widely recommended for multidrug-resistant organisms, contact isolation has raised some concerns that it may bring unintended patient harms. Objective: To compare adverse events between a contact isolation group with vancomycin-resistant Enterococcus (VRE) and a matched comparison group using a relatively large data set from full electronic medical records (EMR) and propensity score-matching methods. Design, Setting, and Participants: This retrospective, matched cohort study was conducted at Seoul National University Bundang Hospital (SNUBH) in Korea, a tertiary, university-affiliated hospital that has 1337 inpatient beds. Participants included a total of 98 529 hospitalized adult patients (aged ≥18 years) during 2015 to 2017. Exposures: Contact isolation in a single or shared double room. Main Outcomes and Measures: As adverse contact isolation-related outcomes, falls and pressure ulcers were included. All relevant EMR data were extracted from the SNUBH clinical data warehouse. Risk factors for adverse events were included in the propensity score model based on literature reviews, such as Braden scale score and Hendrich II fall risk score. A fine stratification and weighting (FSW) and a 1:10 nearest neighbor (NN) propensity score matching as a sensitivity analysis were adopted to compare adverse events between the 2 groups for the observation period from the study entry date and the exit date. Time-to-event analyses with a Cox proportional hazard model were conducted in December 2021. Results: For comparison of outcomes in wards, 177 patients (mean [SD] age, 67.38 [14.12] years; 98 [55.4%] female) with VRE and 93 022 patients (mean [SD] age, 56.44 [16.88] years; 49 462 [53.2%] female) without VRE were included and no difference was found in basic characteristics from the FSW (VRE contact isolation [n = 172] vs comparison [n = 69 434]) as well as from the 1:10 NN (VRE contact isolation [n = 168] vs comparison [n = 1650]). Among 177 patients with VRE contact isolation, 8 pressure ulcers and 3 falls occurred during their hospital stays; incidence rates of adverse events were 2.5 and 0.9 per 1000 patient-days, respectively (pressure ulcer incidence rate from the FSW: 2.53 per 1000 patient-days [95% CI, 1.09-4.99 per 1000 patient-days]; pressure ulcer incidence rate from the 1:10 NN: 2.54 per 1000 patient-days [95% CI, 1.10-5.01 per 1000 patient-days]; fall incidence rate from the FSW: 0.87 per 1000 patient-days [95% CI, 0.18-2.54 per 1000 patient-days]; fall incidence rate from the 1:10 NN: 0.87 per 1000 patient-days [95% CI, 0.18-2.55 per 1000 patient-days]). The hazard ratios for adverse events showed no statistically significant differences for both groups: 1.42 (95% CI, 0.67-2.99) for pressure ulcer and 0.66 (95% CI, 0.20-2.13) for fall from the FSW. Conclusions and Relevance: In this cohort study, no association was found between the likelihood of adverse events and contact isolation using propensity score-matching methods and closely related covariates for adverse events.

Association of asthma comorbidity with poor prognosis of coronavirus disease 2019.

BACKGROUND: While global health agencies have listed asthma as a vulnerability for severe cases of coronavirus disease 2019 (COVID-19), the evidence supporting this is scarce. METHODS: A nationwide cohort study was conducted using the validated Korean national health insurance claim data of patients diagnosed with COVID-19 between January 1 and April 8, 2020. Asthma comorbidity was determined using a diagnosis code assigned by the physician and the prescription of asthma-related medications. The clinical course of COVID-19 was classified into 3 severity grades according to the requirements for oxygen supply and mechanical ventilation. We also evaluated the association of asthma with overall and in-hospital mortality of COVID-19. RESULTS: Asthma morbidity was a significant risk factor for severe COVID-19 (grade 2 requiring oxygen supply) (adjusted odds ratio [aOR] = 1.341, 95% confidence interval [CI], 1.051-1.711, P = 0.018) and grade 3 requiring mechanical ventilation or leading to death (aOR = 1.723, 95% CI: 1.230-2.412, P = 0.002) multinomial logistic regression adjusting co-risk factors. Asthma was also significantly associated with mortality of COVID-19 (aOR = 1.453, 95% CI: 1.015-2.080, P = 0.041) and was revealed to have a shorter time to in-hospital mortality of COVID-19 (P < 0.001). Patients with recent asthma exacerbation showed more severe COVID-19 of grade 3 (OR = 7.371, 95% CI: 2.018-26.924, P = 0.003) and higher mortality (OR = 9.208, 95% CI: 2.597-32.646, P < 0.001) in univariable analysis, but the statistical significance was not found in multivariable analysis. CONCLUSION: Asthma morbidity was associated with severity and mortality of COVID-19. Patients with asthma should pay more attention to avoid worsening of COVID-19.

Lung cancer probability and clinical outcomes of baseline and new subsolid nodules detected on low-dose CT screening.

BACKGROUND: Limited data are available regarding the management of subsolid nodules detected on lung cancer screening with low-dose CT (LDCT). We aimed to determine the characteristics of screen-detected subsolid nodules, and to evaluate the probability of lung cancer and the clinical course of subsolid nodules detected at baseline and during follow-up screening. METHODS: We evaluated 50 132 asymptomatic adults (22 631 never-smokers and 27 501 ever-smokers) who underwent LDCT screening for lung cancer between May 2003 and June 2019 at a tertiary centre in South Korea. The incidence, characteristics and clinical outcomes of the baseline and new screen-detected subsolid nodules were determined. RESULTS: A total of 6725 subsolid nodules (5116 pure ground glass opacity nodules and 1609 part-solid nodules) were detected in 4545 participants (1484 new subsolid nodules detected in 937 (1.9%) participants; the overall incidence of subsolid nodules: 10.7% in never-smokers and 7.7% in ever-smokers, p<0.001). Among 4918 subsolid nodules that underwent follow-up with CT scans (the mean number of CT scans, including the baseline LDCT scan: 4.6), 2116 nodules (30.0% of baseline subsolid nodules and 78.9% of new subsolid nodules) resolved spontaneously. Among 293 biopsied subsolid nodules, 227 (77.5%) nodules were diagnosed as lung cancer, of which 226 (99.6%) were adenocarcinomas. No significant difference was observed in pathological invasiveness or the initial stage between the baseline and new cancerous subsolid nodules. Multivariable analyses revealed that new detection at follow-up screening was significantly associated with a lower probability of lung cancer (OR 0.26, 95% CI 0.14 to 0.49) and overall growth (OR 0.39, 95% CI 0.26 to 0.59), but with a higher probability of resolution (OR 6.30, 95% CI 5.09 to 7.81). CONCLUSIONS: LDCT screening led to a considerably high rate of subsolid nodule detection, particularly in never-smokers. Compared with the baseline subsolid nodules, the new subsolid nodules were associated with a lower probability of lung cancer and higher probability of spontaneous resolution, indicating their more inflammatory nature. Less aggressive follow-up may be allowed for new subsolid nodules, particularly in screening programmes for Asian populations.

Ten-year trends of hypertension treatment and control rate in Korea.

We analyzed the Korean National Health and Nutrition Examination Survey (KNHANES) database to determine the trends of hypertension treatment and control rate in Korea over the past 10 years. In addition, we tried to investigate the effect of chronic medical conditions on hypertension management. We investigated the hypertension prevalence, awareness, treatment, and control rate from 2008 to 2017. KNHANES, which uses a stratified multistage sampling design, is a cross-sectional, nationally representative survey conducted by the Korean government. A total of 59,282 adults (≥ 20 years) were included, which was representative of the total population of around 40 million Koreans per year. The mean age was 50.7 ± 16.4 years and 42.6% were male. The prevalence of hypertension, hypercholesterolemia, diabetes mellitus, and obesity significantly increased over the 10 years. During this period, the hypertension treatment and control rate significantly improved. Hypertension treatment rate was significantly lower in the younger age group compared to the older age group, but the control rate among the treated patients was not significantly different between age groups. The treatment and control rates of hypertension were higher in patients with multimorbidity, which implies that it has a favorable effect on the treatment and control of hypertension. Hypertension treatment and control rate have improved over the past 10 years. The higher treatment and control rate in patients with multimorbidity suggest that the more aggressive surveillance might be associated with the improvement of hypertension treatment and control rate in Korea.

Gender Differences in Patients with Metastatic Pancreatic Cancer Who Received FOLFIRINOX.

BACKGROUND: The combination of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) is a very effective chemotherapeutic regimen for unresectable pancreatic cancer. Previous studies have reported that female gender may be a predictor of a better response to FOLFIRINOX. This study was aimed at investigating the clinical outcomes and dose modification patterns of FOLFIRINOX by gender. METHODS: Patients with metastatic pancreatic cancer (MPC) who began FOLFIRINOX as the first-line therapy at Seoul National University Bundang Hospital between 2013 and 2018 were enrolled. The patients received at least four chemotherapy cycles. Local regression and a linear mixed model were used to analyze dose modification patterns by gender. RESULTS: Ninety-seven patients with MPC (54 men; 43 women) were enrolled. In the first FOLFIRINOX cycle, there were significant differences in age and body surface area between the genders (58.8 (men) and 64.9 years (women), p = 0.005; 1.7 (men) and 1.6 m2 (women), p < 0.001, respectively). The median progression-free survival (PFS) and overall survival (OS) were 10.8 and 18.0 months, respectively. There was a trend of longer PFS (10.3 (men) and 11.9 months (women), p = 0.153) and a significantly longer OS (17.9 (men) and 25.9 months (women), p = 0.019) in female patients. During the first year of FOLFIRINOX treatment, there was a significant difference of the age-corrected dose reduction pattern by gender (a mean of 95.6% dose at the initial cycle and -0.35% of dose reduction per week in men versus a mean of 90.7% dose at the initial cycle and -0.53% of dose reduction per week in women, p-value of the slope: <0.001). There was no difference in the adverse event rates between the genders. CONCLUSIONS: Female patients showed longer OS despite a more rapid dose reduction during each cycle. Gender differences should be considered during FOLFIRINOX treatment.

Toll-like receptor 2 downregulation and cytokine dysregulation predict mortality in patients with Staphylococcus aureus bacteremia.

BACKGROUND: Staphylococcus aureus bacteremia (SAB) presents heterogeneously, owing to the differences in underlying host conditions and immune responses. Although Toll-like receptor 2 (TLR2) is important in recognizing S. aureus, its function during S. aureus infection remains controversial. We aimed to examine the association of TLR2 expression and associated cytokine responses with clinical SAB outcomes. METHODS: Patients from a prospective SAB cohort at two tertiary-care medical centers were enrolled. Blood was sampled at several timepoints (≤5 d, 6-9 d, 10-13 d, 14-19 d, and ≥ 20 d) after SAB onset. TLR2 mRNA levels were determined via real-time PCR and serum tumor necrosis factor [TNF]-α, interleukin [IL]-6, and IL-10 levels were analyzed with multiplex-high-sensitivity electrochemiluminescent ELISA. RESULTS: TLR2 levels varied among 59 SAB patients. On days 2-5, TLR2 levels were significantly higher in SAB survivors than in healthy controls (p = 0.040) and slightly but not significantly higher than non-survivors (p = 0.120), and SAB patients dying within 7 d had lower TLR2 levels than survivors (P = 0.077) although statistically insignificant. IL-6 and IL-10 levels were significantly higher in non-survivors than in survivors on days 2-5 post-bacteremia (P = 0.010 and P = 0.021, respectively), and those dying within 7 d of SAB (n = 3) displayed significantly higher IL-10/TNF-α ratios than the survivors did (P = 0.007). CONCLUSION: TLR2 downregulation and IL-6 and IL-10 concentrations suggestive of immune dysregulation during early bacteremia may be associated with mortality from SAB. TLR2 expression levels and associated cytokine reactions during early-phase SAB may be potential prognostic factors in SAB, although larger studies are warranted.

Hip and Subtrochanteric or Femoral Shaft Fractures after Bisphosphonate Use in Korean Women, Using Korean National Sample Cohort.

BACKGROUND: Concern about bisphosphonate-associated subtrochanteric and femoral shaft (ST/FS) fractures has been raised. However, its real risk is still debatable, because there is no study to estimate risk and benefit of bisphosphonate. The objective of this study was to evaluate the risk of typical hip fractures and ST/FS fractures among bisphosphonate users using nationwide database. METHODS: We performed a retrospective cohort study using National Health Insurance Service-National Sample Cohort. We evaluated occurrence of the ST/FS and femoral neck and intertrochanteric (FN/IT) fractures among female bisphosphonate new users. Incidence rate of ST/FS and FN/IT fractures were compared between long-term users (≥ 1 year) and short-term users (< 1 year). Number needed to harm (NNH) for ST/FS and number needed to treat (NNT) for typical hip fracture were analyzed. RESULTS: Among 46,420 bisphosphonate users, we identified 14,689 long-term users and 21,840 short-term users. During the study period, 61 long-term users and 36 short-term users had ST/FS fractures, while 204 long-term users and 511 short-term users had FN/IT fractures. The long-term user showed higher incidence rate of ST/FS fractures (67.1/100,000 person-years; 95% confidence interval [CI], 50.3-83.9) comparing with 31.2/100,000 person-years (95% CI, 21.0-41.4) in the short-term users. The incidence rate of FN/IT fractures was 225.5/100,000 person-years (95% CI, 194.6-256.5) in the long-term users and 448.6/100,000 person-years (95% CI, 409.7-487.5) in the short-term users. The NNH for ST/FS was 400, while the NNT for typical hip fracture was 105. CONCLUSION: Our study suggested that physicians keep the significant benefit of bisphosphonate to prevent typical hip fracture in mind, even the concerns about bisphosphonate-associated ST/FS fractures.

A population-based observational study of patients with pulmonary disorders in intensive care unit.

BACKGROUND/AIMS: Only a few epidemiologic studies on the patients with pulmonary disorders admitted to intensive care unit exist. We investigated the characteristics and clinical outcomes of the patients with severe pulmonary disorders. METHODS: The sample cohort database of National Health Insurance Sharing Service from 2006 to 2015 was used. Operational definition of critically ill patients was adults who were either admitted to intensive care unit for at least 3 days or expired within first 2 days in the unit. The pulmonary disorder group comprised of critically ill patients with respiratory disease as the main diagnosis. RESULTS: Among the 997,173 patients, 12,983 (1.3%) in 383 intensive care units were categorized as critically ill. Patients in the pulmonary disorder group tended to have more comorbidities or disabilities. The length of hospital stay and duration of mechanical ventilation were longer in the pulmonary disorder group. Overall mortality and re-admission were higher in the pulmonary disorder group, with adjusted incidence rate ratios of 1.22 (95% confidence interval, 1.18 to 1.27) and 1.26 (95% confidence interval, 1.17 to 1.36), respectively. After adjustment by Cox regression, the pulmonary disorder group was an independent risk factor for in-hospital mortality. CONCLUSION: In critically ill patients with pulmonary disorder, the use of healthcare resources was higher, and their clinical outcomes were significantly worse than the non-pulmonary disorder group.

The effect of neuromuscular reversal agent on postoperative pain after laparoscopic gastric cancer surgery: Comparison between the neostigmine and sugammadex.

Use of sugammadex for neuromuscular block reversal is associated with fewer postoperative complications than neostigmine; however, the effects on postoperative pain outcomes are largely unknown. In this retrospective study, we investigated the relationship between neuromuscular reversal agents and postoperative pain-related outcomes following laparoscopic gastric cancer surgery.We reviewed the electronic health records of patients who underwent laparoscopic gastric cancer surgery between January 2010 and June 2017. Patients were divided into a sugammadex group and a neostigmine group, according to the neuromuscular block reversal agent used. We compared the pain outcomes in the first 3 days postoperatively (POD 0-3), length of hospital stay, and postoperative complications (Clavien-Dindo grade ≥II).During the study period, 3056 patients received sugammadex (n = 901) or neostigmine (n = 2155) for neuromuscular reversal. After propensity score matching, 1478 patients (739 in each group) were included in regression analysis. In linear regression analysis, intravenous morphine equivalent consumption (mg) during POD 0 to 3 was higher in the sugammadex group than in the neostigmine group [coefficient 103.41, 95% confidence interval (CI): 77.45-129.37; P <.001]. However, hospital stay was shorter (coefficient: -0.60, 95% CI -1.12 to -0.08; P = .025) and postoperative complication rate was lower (odds ratio: 0.20, 95% CI 0.07-0.58; P = .003) in the sugammadex group.In this retrospective study, patients undergoing laparoscopic gastric cancer surgery who received sugammadex for neuromuscular block reversal exhibited greater postoperative analgesic requirements than those who received neostigmine but had a shorter hospital stay and a lower postoperative complication rate. A randomized and blinded study should be conducted in the future to confirm the findings of the present study.

Effect of sevoflurane-based or propofol-based anaesthesia on the incidence of postoperative acute kidney injury: A retrospective propensity score-matched analysis.

BACKGROUND: Propofol may help to protect against ischaemic acute kidney injury (AKI); however, research on this topic is sparse. OBJECTIVE: The current study aimed to investigate whether there were differences in the incidence of postoperative AKI after lung resection surgery between patients who received propofol-based total intravenous anaesthesia (TIVA) and those who received sevoflurane-based inhalational anaesthesia. DESIGN: A retrospective observational study. SETTING: A single tertiary care hospital. PATIENTS: Medical records of patients aged 19 years or older who underwent curative lung resection surgery for nonsmall cell lung cancer between January 2005 and February 2018 were examined. MAIN OUTCOME MEASURES: After propensity score matching, the incidence of AKI in the first 3 postoperative days was compared between patients who received propofol and those who received sevoflurane. Logistic regression analyses were also used to investigate whether propofol-based TIVA lowered the risk of postoperative AKI. RESULTS: The analysis included 2872 patients (1477 in the sevoflurane group and 1395 in the propofol group). After propensity score matching, 661 patients were included in each group; 24 (3.6%) of the 661 patients in the sevoflurane group developed AKI compared with 23 (3.5%) of the 661 patients in the propofol group (95% confidence intervals of difference in incidence -0.019 to 0.022, P = 0.882). The logistic regression analyses revealed that the incidence of AKI was not different in the two groups (odds ratio 0.96, 95% confidence interval 0.53 to 1.71, P = 0.882). CONCLUSION: In this retrospective study, no significant difference was found in the incidence of postoperative AKI after lung resection surgery between patients who received propofol-based TIVA and those who received sevoflurane-based inhalational anaesthesia. Considering the methodological limitation of this retrospective study, further studies are required to confirm these results.

Association between intraoperative magnesium sulfate infusion and mortality after non-cardiac surgery: a retrospective propensity score matched analysis.

The short-term effects of magnesium sulfate infusion during surgery are well known. However, the long-term outcomes of intraoperative magnesium sulfate infusion remain unknown. Medical records of patients aged ≥20 years who underwent non-cardiac surgical procedures at Seoul National University Bundang Hospital between January, 2010 and October, 2016 were analyzed. After propensity score matching, 12,652 patients were included in the final analysis, 6326 each in the magnesium and non-magnesium groups. There were no significant differences in 30-day or 1-year mortality between subjects [30-day mortality, hazard ratio (HR): 1.31, 95% CI: 0.64-2.69, P = 0.465; 1-year mortality, HR: 1.20, 95%CI: 0.94-1.53, P = 0.136]. Intraoperative magnesium sulfate infusion was not significantly associated with postoperative 30-day or 1-year mortality.