Proton pump inhibitor therapy and risk of knee replacement surgery: a general population-based cohort study.

OBJECTIVE: Proton pump inhibitors (PPIs) are among the most commonly used medications for patients with osteoarthritis (OA). Various types of PPIs have different impacts on lowering serum magnesium level that may affect knee OA progression. We aimed to compare the risk of clinically relevant endpoint of knee replacement (KR) among initiators of five different PPIs with that among histamine-2 receptor antagonist (H2RA) initiators. DESIGN: Among patients with knee OA (≥50 years) in The Health Improvement Network database in the UK we conducted five sequential propensity-score matched cohort studies to compare the risk of KR over 5-year among patients who initiated omeprazole (n = 2,672), pantoprazole (n = 664), lansoprazole (n = 3,747), rabeprazole (n = 751), or esomeprazole (n = 827) with those who initiated H2RA. RESULTS: The prevalence of PPI prescriptions among participants with knee OA increased from 12.7% in 2000-44.0% in 2017. Two-hundred-and-seventy-four KRs (30.8/1,000 person-years) occurred in omeprazole initiators and 230 KRs (25.4/1,000 person-years) in H2RA initiators. Compared with H2RA initiators, the risk of KR was 21% higher in omeprazole initiators (hazard ratio [HR] = 1.21,95% confidence interval [CI]:1.01-1.44). Similar results were observed when pantoprazole use was compared with H2RA use (HR = 1.38,95%CI:1.00-1.90). No such an increased risk of KR was observed among lansoprazole (HR = 1.06,95%CI:0.92-1.23), rabeprazole (HR = 0.97,95%CI:0.73-1.30), or esomeprazole (HR = 0.83,95%CI:0.60-1.15) initiators compared with that among H2RA initiators. CONCLUSIONS: In this population-based cohort study, initiation of omeprazole or pantoprazole use was associated with a higher risk of KR than initiation of H2RA use. This study raises concern regarding an unexpected risk of omeprazole and pantoprazole on accelerating OA progression.

Association of tramadol with risk of myocardial infarction among patients with osteoarthritis.

OBJECTIVE: Tramadol has been widely used among patients with osteoarthritis (OA); however, there is paucity of information on its cardiovascular risk. We aimed to examine the association of tramadol with risk of myocardial infarction (MI) among patients with OA. DESIGN: Among OA patients aged 50-90 years without history of MI, cancer, or opioid use disorder in The Health Improvement Network database in the United Kingdom (2000-2016), three sequential propensity-score matched cohort studies were assembled, i.e., (1) patients who initiated tramadol or naproxen (negative comparator); (2) patients who initiated tramadol or diclofenac (positive comparator); and (3) patients who initiated tramadol or codeine (a commonly used weak opioid). The outcome was incident MI over six-months. RESULTS: Among tramadol and naproxen initiators (n = 33,024 in each cohort), 77 (4.8/1000 person-years) and 46 (2.8/1000 person-years) incident MI occurred, respectively. The rate difference (RD) and hazard ratios (HR) for incident MI with tramadol initiation were 1.9 (95% confidence interval [CI] 0.6 to 2.3)/1000 person-years and 1.68 (95% CI 1.16 to 2.41) relative to naproxen initiation, respectively. Among tramadol and diclofenac initiators (n = 18,662 in each cohort), 58 (6.4/1000 person-years) and 47 (5.1/1000 person-years) incident MIs occurred, respectively. The corresponding RD and HR for incident MI were 1.2 (95%CI -2.1 to 14.1)/1000 person-years and 1.24 (95%CI 0.84 to 1.82), respectively. Among tramadol and codeine initiators (n = 42,722 in each cohort), 127 (6.1/1000 person-years) and 103 (5.0/1000 person-years) incident MI occurred, respectively, and the corresponding RD and HR were 1.1 (95%CI:-0.3 to 2.5)/1000 person-years and 1.23 (95%CI:0.95 to 1.60), respectively. CONCLUSIONS: In this population-based cohort of patients with OA, the six-month risk of MI among initiators of tramadol was higher than that of naproxen, but comparable to, if not lower than, those of diclofenac or codeine.

Thiazide diuretics and risk of knee replacement surgery among patients with knee osteoarthritis: a general population-based cohort study.

OBJECTIVE: Thiazide diuretic use is associated with higher bone mineral density (BMD) and possibly lower serum magnesium levels than loop diuretic use, and both high BMD and low serum magnesium have been linked to high prevalent knee osteoarthritis. This study aimed to compare the risk of a clinically relevant endpoint, knee replacement (KR) surgery, among initiators of thiazide and loop diuretics. DESIGN: Among patients aged ≥50 years with a diagnosis of knee osteoarthritis in The Health Improvement Network (THIN) in United Kingdom, we conducted a propensity score-matched cohort study to examine the relation of thiazide diuretic initiation vs loop diuretic initiation to the risk of KR over 5 years. RESULTS: Among thiazide and loop diuretic initiators (n = 3,488 for each group; mean age: 73 years; female ratio: 59%), 359 (28.6/1,000 person-years) and 283 (24.1/1,000 person-years) KRs occurred during the follow-up period, respectively. The hazard ratio (HR) of KR for thiazide diuretic initiation vs loop diuretic initiation was 1.26 (95% confidence interval [CI]: 1.08-1.47). The adherence-adjusted HR of KR for continuous use of thiazide diuretics was 1.44 (95% CI: 1.21-1.72). CONCLUSIONS: In this population-based cohort of patients with knee osteoarthritis, thiazide diuretic use was associated with a higher risk of KR than loop diuretic use. This association may potentially be due to thiazide diuretics' effect on BMD and serum magnesium.

Risk factor heterogeneity for medial and lateral compartment knee osteoarthritis: analysis of two prospective cohorts.

OBJECTIVE: To evaluate the etiologic heterogeneity between medial and lateral tibiofemoral radiographic osteoarthritis (ROA). METHODS: Knees without medial or lateral tibiofemoral ROA at baseline were followed for 60-month in Multicenter Osteoarthritis Study (MOST) and for 48-month in Osteoarthritis Initiative (OAI). We examined the relation of previously reported risk factors to incident medial and lateral tibiofemoral ROA separately and determined the etiology heterogeneity with a ratio of rate ratios (RRs) (i.e., the RR for medial tibiofemoral ROA divided by the RR for lateral tibiofemoral ROA) using a duplication method for Cox proportional hazard regression. RESULTS: Of 2,016 participants in MOST, 436 and 162 knees developed medial or lateral tibiofemoral ROA, respectively. Obesity and varus malalignment were 95% and 466% more strongly associated with incident medial tibiofemoral ROA than with lateral tibiofemoral ROA, respectively (ratios of RRs, 1.95 [95% confidence interval (CI):1.05-3.62] and 5.66 [95% CI:3.20-10.0]). In contrast, the associations of female sex and valgus malalignment with incident medial tibiofemoral ROA were weaker or in an opposite direction compared with lateral tibiofemoral Osteoarthritis (OA) (ratios of RRs, 0.40 [95% CI:0.26-0.63] and 0.20 [95% CI:0.12-0.34], respectively). Older age tended to show a weaker association with incident medial tibiofemoral ROA than with incident lateral tibiofemoral ROA. No heterogeneity was observed for the relation of race, knee injury, or contralateral knee ROA. These findings were closely replicated in OAI. CONCLUSION: Risk factor profiles for medial and lateral tibiofemoral ROA are different. These results can provide a framework for the development of targeted prevention and potential treatment strategies for specific knee OA subtypes.

Intra-articular corticosteroids and the risk of knee osteoarthritis progression: results from the Osteoarthritis Initiative.

OBJECTIVE: A recent randomized clinical trial reported that repeated intra-articular corticosteroids (IACs) were associated with a greater cartilage loss. This study aimed to examine the relation of IACs to knee radiographic osteoarthritis (ROA) progression in a real-world setting. DESIGN: A cohort that initiated IACs and a comparison cohort without IACs from participants with mild to moderate knee ROA in the Osteoarthritis Initiative (OAI) were assembled (from 0-month to 48-month). Two measures of knee ROA progression were assessed during the follow-up period: (1) an increase in Kellgren and Lawrence (KL) grade by ≥1 grade or having a knee replacement (i.e., KL grade worsening); and (2) a decrease in joint space width (JSW) by ≥0.7 mm or having a knee replacement (i.e., JSW worsening). The associations of IACs initiation using a propensity-score matched cohort study and continuous IACs using marginal structural models with the risk of knee ROA progression were examined. RESULTS: Among 684 propensity-score matched participants at baseline (148 IACs initiators, 536 comparators), 65 knees (21.7/100 person-years) in the IACs initiation cohort and 90 knees (7.1/100 person-years) in the comparison cohort experienced KL worsening. The hazard ratios (HRs) of KL worsening from IACs initiation and continuous IACs were 3.02 (95% confidence interval [CI], 2.19-4.16) and 4.67 (95% CI, 2.92-7.47), respectively. The corresponding HRs of JSW worsening were 2.93 (95% CI, 2.13-4.02) and 3.26 (95% CI, 1.78-5.96), respectively. All HRs for continuous use of IACs were further away from the null. CONCLUSIONS: IACs, especially continuous IACs, may be associated with an increased risk of knee ROA progression.

The value of neck drain in esophageal surgery: a randomized trial.

The use of surgical drains in certain clean elective operations remains controversial. To evaluate the role of closed-suction drain for an esophageal anastomosis in the neck, we conducted a randomized, controlled study in 40 patients with esophageal carcinoma who underwent esophagectomy with an esophageal anastomosis in the neck, half of whom had a neck drain inserted at the end of operation. The median (range) duration of drainage was 46 hours (36 to 88 hours). The median (range) amount of drainage was 63 ml (15 to 210 ml). There was no incidence of haematoma or seroma formation in both the drained and non-drained groups. Anastomotic leakage did not occur in any patient. The benefits of closed suction neck drain could not be demonstrated. Routine use of neck drain for esophageal anastomosis in the neck is not necessary.

Randomized clinical trial of chewing gum after laparoscopic colorectal resection.

BACKGROUND: Chewing gum may enhance intestinal motility after surgery. This trial studied whether chewing gum could lead to a further reduction in ileus in patients who had a laparoscopic colorectal resection and followed an enhanced recovery programme. METHODS: Patients undergoing laparoscopic colorectal resection were randomized to a control or intervention group. Patients in the control group received a standardized recovery programme. Patients in the intervention group were, in addition, given chewing gum three times daily from day 1 until discharge. Primary outcome measures were time to first flatus and first bowel motion. Time to feeling hungry and hospital stay were secondary outcome measures. RESULTS: Forty-one patients were randomized into each group. Thirty-seven patients underwent rectal resection and 45 had a colonic resection. Time to passage of flatus was shorter (18 versus 34 h; P = 0·007), first bowel motion occurred earlier (19 versus 44 h; P = 0·001) and time to feeling hungry was earlier (16 versus 25 h; P = 0·001) in the intervention group. There was no difference in the duration of hospital stay (5 days in the intervention group versus 5·5 days in the control group). Subgroup analyses revealed that the benefits of chewing gum were clearer in patients who had a colonic resection, with a shorter time to first flatus (20 versus 35 h; P = 0·043), first bowel motion (19 versus 53 h; P = 0·014) and feeling hungry (14 versus 40 h; P = 0·001). No adverse events were attributed to chewing gum. CONCLUSION: Chewing gum is a simple intervention that speeds intestinal transit in patients managed with a recovery programme after laparoscopic colorectal resection. REGISTRATION NUMBER: NCT02419586 (https://clinicaltrials.gov/).

Plasma uric acid concentrations and risk of ischaemic stroke in women.

BACKGROUND AND PURPOSE: Elevated plasma uric acid has been inconsistently associated with an increased risk of total stroke; however, data are sparse amongst women. The association between plasma uric acid concentrations and ischaemic stroke amongst women was examined and the effect modification by key cardiovascular risk factors was evaluated. METHODS: A nested case-control design with matching by age, race/ethnicity, smoking status, menopausal status, postmenopausal hormone therapy use, date of blood draw and fasting status was utilized amongst female participants of the Nurses' Health Study who provided blood samples between 1989 and 1990. Plasma uric acid was measured on stored blood samples. The National Survey of Stroke criteria were utilized to confirm 460 incident cases of ischaemic stroke by medical records from 1990 to 2006. Multivariable conditional logistic regression models were estimated. RESULTS: In matched analysis, risk of ischaemic stroke increased by 15% for each 1 mg/dl increase in plasma uric acid [95% confidence interval (CI) 3%-28%], but was no longer significant after adjustment for cardiovascular risk factors, particularly history of hypertension. The highest quartile of uric acid was significantly associated with greater risk of ischaemic stroke (relative risk 1.56; 95% CI 1.06-2.29, extreme quartiles) in matched analysis, but estimates were no longer significant after adjustment for cardiovascular risk factors (relative risk 1.43; 95% CI 0.93-2.18). Significant effect modification by key cardiovascular risk factors was not observed. CONCLUSIONS: Plasma uric acid levels were not independently associated with increased risk of ischaemic stroke in this cohort of women. Whilst plasma uric acid was associated with stroke risk factors, it was not independently associated with stroke risk.

Performance of PCR-REBA assay for screening and identifying pathogens directly in whole blood of patients with suspected sepsis.

AIMS: Rapid and accurate identification of a broad range of bacterial and fungal pathogens is the key to successful management of patients with bloodstream infections (BSIs). The aim of this study was to evaluate the diagnostic performance of PCR-REBA Sepsis-ID test for the detection of BSIs pathogens. METHODS AND RESULTS: EDTA anticoagulated blood for REBA Sepsis-ID assay and blood culture samples from 882 patients with suspected sepsis were simultaneously collected from January 2014 to December 2014. Of 115 patients with positive blood culture, 64 (55·7%) were Gram-positive bacteria, 35 (30·4%) were Gram-negative bacteria, 1 (0·9%) was Candida albicans and 15 (13·0%) were polymicrobial infections. The concordance rate of blood culture system and PCR-REBA Sepsis ID test was 83·0% (95% confidence interval (CI), 79·8-84·8, P < 0·0001). Compared to blood culture, the diagnosis of bacterial proven pathogens by PCR-REBA revealed 81·0% (95% CI, 73·4-86·8, P < 0·0001) sensitivity, 83·4% (95% CI, 80·0-85·4, P < 0·0001) specificity, 80·9% positive and 95·8% negative predictive values respectively. In 10 cases with PCR-REBA positive but blood culture negative, the levels of C-reactive protein were significantly elevated 18·5 mg dl(-1) (SD ± 13·7, 95% CI 1·8-41·9) and six cases has been proven to have pathogen by bacterial 16S rRNA sequencing. Although the sensitivity for pathogen identification was not significantly different between PCR-REBA and blood culture (P = 0·5), the combination of the two methods resulted in a significantly increased rate of pathogen detection (P = 0·002). The results of this study suggested that PCR-REBA may be helpful when added to blood culture in the diagnosis and management of sepsis. CONCLUSIONS: PCR-REBA Sepsis-ID test is a useful tool for the rapid identification of pathogenic isolates in whole blood to ensure adequate treatment for the causative agents of BSIs. SIGNIFICANCE AND IMPACT OF THE STUDY: Although the cost of molecular diagnostic assays is higher than the cost of conventional methods, clinical and economic cost-benefit analysis is still needed. PCR-REBA may provide essential information for accelerating therapeutic decisions to ensure effective treatment with antibiotics in the acute phase of pathogen infection.

Incident long-term warfarin use and risk of osteoporotic fractures: propensity-score matched cohort of elders with new onset atrial fibrillation.

UNLABELLED: Association between warfarin use and fracture risk is unclear. We examined the association between long-term warfarin use and fracture risk at the hip, spine, and wrist in elders. No significant association was found between long-term warfarin use and fracture risk, despite biological plausibility. INTRODUCTION: Prior studies examining the association of warfarin use and osteoporotic fractures have been conflicting, potentially related to methodological limitations. Thus, we examined the association of long-term warfarin use with risk of hip, spine, and wrist fractures among older adults with atrial fibrillation, attempting to address prior methodologic challenges. METHODS: We included men and women ≥ 65 years of age with incident atrial fibrillation and without prior history of fractures from The Health Improvement Network followed between 2000 and 2010. Long-term warfarin use was defined in two ways: (1) warfarin use ≥ 1 year; (2) warfarin use ≥ 3 years. Propensity-score matched cohorts of warfarin users and nonusers were created to evaluate the association between long-term warfarin use and risk of hip, spine, and wrist fractures separately as well as combined, using Cox-proportional hazards regression models. RESULTS: Among >20,000 participants with incident atrial fibrillation, the hazard ratios (HR) for hip fracture with warfarin use ≥ 1 and ≥ 3 years, respectively, were 1.08 (95%CI 0.87, 1.35) and 1.13 (95% CI 0.84, 1.50). Similarly, no significant associations were observed between long-term warfarin use and risk of spine or wrist fracture. When risk of any fracture was assessed with warfarin use, no association was found [HR for warfarin use ≥ 1 year 0.92 (95%CI 0.77, 1.10); HR for warfarin use ≥ 3 years 1.12 (95%CI 0.88, 1.43)]. CONCLUSIONS: Long-term warfarin use among elders with atrial fibrillation was not associated with increased risk of osteoporotic fractures and therefore does not appear to necessitate additional surveillance or prophylaxis.

Charge frustration in a triangular triple quantum dot.

We experimentally investigate the charge (isospin) frustration induced by a geometrical symmetry in a triangular triple quantum dot. We observe the ground-state charge configurations of sixfold degeneracy, the manifestation of the frustration. The frustration results in omnidirectional charge transport, and it is accompanied by nearby nontrivial triple degenerate states in the charge stability diagram. The findings agree with a capacitive interaction model. We also observe unusual transport by the frustration, which might be related to elastic cotunneling and the interference of trajectories through the dot. This work demonstrates a unique way of studying geometrical frustration in a controllable way.

Controlled dephasing of an electron interferometer with a path detector at equilibrium.

Controlled dephasing of electrons, via "which path" detection, involves, in general, coupling a coherent system to a current driven noise source. However, here we present a case in which a nearly isolated electron puddle within a quantum dot, at thermal equilibrium and in millikelvin range temperature, fully dephases the interference in a nearby electronic interferometer. Moreover, the complete dephasing is accompanied by an abrupt π phase slip, which is robust and nearly independent of system parameters. Attributing the robustness of the phenomenon to the Friedel sum rule--which relates a system's occupation to its scattering phases--proves the universality of this powerful rule. The experiment allows us to peek into a nearly isolated quantum dot, which cannot be accessed via conductance measurements.

Characterization of filamentous bacteriophage PE226 infecting Ralstonia solanacearum strains.

AIMS: The aim of this study was to isolate and characterize new bacteriophages that infect a wide range of plant pathogenic Ralstonia solanacearum strains. METHODS AND RESULTS: Fifteen bacteriophages were isolated from pepper, tomato and tobacco plant rhizospheres infected with R. solanacearum. A host specificity analysis of the isolated phages using nine strains of R. solanacearum indicated great phage diversity in a single soil. Two phages, PE226 and TM227, showed clear plaques on all nine bacterial hosts tested and were virtually identical in morphology and genome. PE226, an Inovirus, is a long, flexible, filamentous phage carrying a circular (+) sense single-strand DNA genome of 5475 nucleotides. DNA sequences of PE226 exhibited nine open reading frames (ORF) that were not highly similar to those of other phages infecting R. solanacearum. The genome organization of PE226 was partially similar to that of p12J of Ralstonia pickettii. One ORF of PE226 showed identity to the zot gene encoding zonula occludens toxin of Vibrio cholera. Orf7 of PE226 was also present in the genome of R. solanacearum strain SL341. However, SL341, a highly virulent strain in tomato, was still sensitive to phage PE226. CONCLUSIONS: A new, flexible, filamentous phage PE226 infected wide range of R. solanacearum strains and carried unique circular single-strand DNA genome with an ORF encoding Zot-like protein. SIGNIFICANCE AND IMPACT OF THE STUDY: PE226 may be a new type of temperate phage, based on its lytic nature on a wide range of hosts and the presence of a zot homologue in a host bacterial genome.

Immune regulatory effects of simvastatin on regulatory T cell-mediated tumour immune tolerance.

Statins are potent inhibitors of hydroxyl-3-methylglutaryl co-enzyme A (HMG-CoA) reductase, and have emerged as potential anti-cancer agents based on preclinical evidence. In particular, compelling evidence suggests that statins have a wide range of immunomodulatory properties. However, little is known about the role of statins in tumour immune tolerance. Tumour immune tolerance involves the production of immunosuppressive molecules, such as interleukin (IL)-10, transforming growth factor (TGF)-beta and indoleamine-2,3-dioxygenase (IDO) by tumours, which induce a regulatory T cell (T(reg)) response. In this study, we investigated the effect of simvastatin on the production of IL-10, TGF-beta and IDO production and the proliferation of T(regs) using several cancer cell lines, and Lewis lung cancer (3LL) cells-inoculated mouse tumour model. Simvastatin treatment resulted in a decrease in the number of cancer cells (3LL, A549 and NCI-H292). The production of the immune regulatory markers IL-10, TGF-beta in 3LL and NCI-H292 cells increased after treatment with simvastatin. The expression of IDO and forkhead box P3 (FoxP3) transcription factor was also increased in the presence of simvastatin. In a murine 3LL model, there were no significant differences in tumour growth rate between untreated and simvastatin-treated mice groups. Therefore, while simvastatin had an anti-proliferative effect, it also exhibited immune tolerance-promoting properties during tumour development. Thus, due to these opposing actions, simvastatin had no net effect on tumour growth.

Diagnosis of Pierce's disease using biomarkers specific to Xylella fastidiosa rRNA and Vitis vinifera gene expression.

Pierce's disease (PD), caused by Xylella fastidiosa, represents one of the most damaging diseases of cultivated grape. Management of PD in the vineyard often relies on the removal of infected individuals, which otherwise serve as a source of inoculum for nearby healthy vines. Effective implementation of such control measures requires early diagnosis, which is complicated by the fact that infected vines often harbor high titers of the pathogen in advance of visual symptom development. Here, we report a biomarker system that simultaneously monitors Xylella-induced plant transcripts as well as Xylella ribosomal (r)RNA. Plant biomarker genes were derived from a combination of in silico analysis of grape expressed sequence tags and validation by means of reverse-transcriptase polymerase chain reaction (RT-PCR). Four genes upregulated upon PD infection were individually multiplexed with an X. fastidiosa marker rRNA and scored using either real-time RT-PCR or gel-based conventional RT-PCR techniques. The system was sufficiently sensitive to detect both host gene transcript and pathogen rRNA in asymptomatic infected plants. Moreover, these plant biomarker genes were not induced by water deficit, which is a component of PD development. Such biomarker genes could have utility for disease control by aiding early detection and as a screening tool in breeding programs.

The incidence and seasonal variation of necrotizing fasciitis in Korea: a nationwide cross-sectional study.

INTRODUCTION: Necrotizing fasciitis (NF) is a rare but fatal disease, and there is no known annual incidence of NF in Korea. The aim of this study was to investigate the incidence and seasonal variation of NF in Korea. METHODS: We analysed claims from the nationwide Korean Health Insurance Review and Assessment Service database. Patients who were hospitalized with an NF diagnosis code and received surgical intervention were classified as NF cases. Poisson regression models were used to assess the relationships of incidence rates with year, age and sex. A multivariate Poisson regression model was used to investigate variations in monthly NF incidence trends. RESULTS: From 2012 to 2017, the overall average annual NF incidence rate was found to be 0.86 per 100 000 population. NF incidence increased with age and was 2.5 times higher among males across all age groups. Two-thirds of cases occurred among patients with diabetes. The peak NF incidence occurred during the summer. Multivariate Poisson regression modelling using national meteorological variables suggested that mean temperatures and number of NF cases in the previous month were associated with the number of NF cases in the current month. DISCUSSION: Clinicians should consider NF when encountering an elderly man with diabetes during the summer.

Two different variants of the jugulocephalic vein with supraclavicular course.

The jugulocephalic anastomosis is a rare anatomical variant which normally undergoes atrophy during embryonic development. We found 2 cases of the jugulocephalic vein variant with supraclavicular course in Korean male cadavers. In a 50-year-old cadaver, the right cephalic vein ascended anterior to the clavicle, and terminated into the external jugular vein as well as to the axillary vein through a classic branch. In a 76-year-old cadaver, the left cephalic vein ascended supraclavicular course without any branch to the axillary vein, and terminated to the external jugular vein. We discussed the embryological explanation as well as its frequency since this jugulocephalic vein variant could cause unpredicted danger during clinical procedures.

Timing of antibiotics in septic patients: a prospective cohort study.

OBJECTIVES: To evaluate the effect of timing and appropriateness of antibiotics administration on mortality in patients diagnosed with sepsis according to the Sepsis-3 definition. METHODS: This prospective cohort study was conducted in patients diagnosed with sepsis according to the Sepsis-3 definition at the emergency department of Korea University Ansan Hospital from January 2016 to January 2019. The time to antibiotics was defined as the time in hours from emergency department arrival to the first antibiotic administration. Cox proportional hazards regression analysis was used to estimate the association between time to antibiotics and 7-, 14- and 28-day mortality. RESULTS: Of 482 patients enrolled onto this study, 203 (42.1%) of 482 and 312 (64.7%) of 482 were diagnosed with septic shock and high-grade infection respectively. The median time to receipt of antibiotic therapy was 115 minutes. Antibiotics were administered within 3 and 6 hours in 340 (70.4%) of 482 and 450 (93.2%) of 482 patients respectively. Initial appropriate empirical antibiotics were administered in 375 (77.8%) of 482 patients. The time to and appropriateness of the initial antibiotics were not associated with 7-, 14- and 28-day mortality in multivariate analysis. The Sequential Organ Failure Assessment (SOFA) score (adjusted hazard ratio (aHR) 1.229, 95% confidence interval (CI) 1.093-1.381, p 0.001) and initial lactate levels (aHR 1.128, 95% CI 1.034-1.230, p 0.007), Charlson comorbidity index (aHR 1.115, 95% CI 1.027-1.210, p 0.014), 2-hour lactate level (aHR 1.115, 95% CI 1.027-1.210, p 0.009) and SOFA score (aHR 1.077, 95% CI 1.013-1.144, p 0.018) affected 7-, 14- and 28-day mortality respectively. Subgroup analysis with septic shock, bacteraemia and high-grade infection did not affect mortality rates. CONCLUSIONS: Time to receipt of antibiotics may not affect the prognosis of patients with sepsis if a rapid and well-trained resuscitation is combined with appropriate antibiotic administration within a reasonable time.

Dual energy computed tomography in tophaceous gout.

OBJECTIVE: To evaluate the potential utility of a dual energy CT (DECT) scan in assessing urate deposits among patients with tophaceous gout, and obtain computerised quantification of tophus volume in peripheral joints. METHODS: 20 consecutive patients with tophaceous gout and 10 control patients with other arthritic conditions were included. DECT scans were performed using a renal stone colour-coding protocol that specifically assessed the chemical composition of the material (ie, urate coloured in red, calcium coloured in blue). An automated volumetric assessment of DECT was used to measure the volume of urate deposits in all peripheral joint areas. RESULTS: All 20 patients with gout showed red colour-coded urate deposits on their DECT scans, whereas none of 10 controls showed urate deposits. DECT scans revealed a total of 440 areas of urate deposition in 20 patients, whereas physical examination showed 111 areas of urate deposition (mean 22 vs 6 per patient, respectively, p<0.001). Total urate volume in a given patient ranged from 0.63 cm(3) to 249.13 cm(3), with a mean of 40.20 cm(3). CONCLUSIONS: DECT scans can produce obvious colour displays for urate deposits and help to identify subclinical tophus deposits. Furthermore, tophus volume can be measured by DECT scans through an automated volume estimation procedure.