Metformin activates AMPK and mTOR to Inhibit RANKL-stimulated osteoclast formation.

OBJECTIVE: Metformin is a medication used to treat type 2 diabetes by inhibiting hepatic glucose production through adenosine monophosphate-activated protein kinase (AMPK) activation. Autophagy is closely related to the homeostasis and stress mechanisms of the body. In recent years, much research has arisen on therapeutic methods utilizing autophagy mechanisms to treat diagnoses such as metabolic diseases, tumors, and Alzheimer's disease. This study thus aimed to investigate the effects of metformin treatment on the differentiation of osteoclasts and changes in AMPK mechanisms, which play an important role in regulating energy homeostasis, and mTOR, a highly conserved kinase that regulates autophagy. MATERIALS AND METHODS: Experimentation, including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, tartrate-resistant acid phosphate (TRAP) staining, pit formation assay, immunofluorescence, western blotting, and real-time polymerase chain reaction (PCR) was performed to investigate the effects of metformin on osteoclast differentiation. Additionally, to investigate its association with AMPK and pathways, the AMPK inhibitor compound C and mammalian targets of rapamycin (mTOR) activator leucine were used to examine the expression of osteoclast- or autophagy-related proteins, genes, and TRAP-positive cells. RESULTS: Metformin showed no cytotoxic effects on mouse osteoblastic cell lines (MC3T3-E1) and murine macrophage cell lines (RAW264.7) but did inhibit osteoclast differentiation. Furthermore, metformin was found to inhibit osteoclast differentiation through AMPK activation and mTOR inhibition. In turn, AMPK inhibition using compound C promoted osteoclast differentiation, and mTOR activation using leucine inhibited autophagy and osteoclast differentiation. CONCLUSIONS: Metformin activates the AMPK pathway while functioning as an activator of mTOR, thereby leading to the inhibition of autophagy and osteoclast differentiation.

Influence of 12 weeks of basketball training on college students' heart function.

OBJECTIVE: This study aims to investigate the influence of 12 weeks of basketball training on college students' heart function. SUBJECTS AND METHODS: The subjects were 30 college male basketball players. Carry out 8-week interval training, monitor the training load and interval time of athletes, and strictly control the heart rate during the interval. Before and after training, we used safe and effective experimental instruments - without any damage to the athletes - to detect the relevant indicators of the athletes' physiological functions; hence we compared and analyzed the various indicators before and after training. RESULTS: The time domain indexes Root Mean Square of Successive Differences (RMSSD), Statistically Determined Spatial Drift (SDSD), percentage of NN50 in the total number of NN intervals (PNN50), and Standard Deviation of all NN intervals for all 5-min segment (SDNN) after training were significantly higher than those before training, and the differences were statistically significant (p<0.05). Average (Avag) and Statistically Determined Allocation Weights (SDAW) after training were significantly higher than those before training, the difference was statistically significant (p<0.05); Asymmetry (Asym) and Tension index (TI) were significantly lower than those before training, the difference was statistically significant (p<0.05), Application Information Index (ApInf) had no significant difference (p>0.05). There was no significant difference in shooting hit rate (p>0.05). The speed of the 8-character dribble in the whole field after training was significantly lower than that before training, and the differences were statistically significant (p<0.05). There was no significant difference in average jump height, maximum jump height, average time in the air, and best jump time in the air after training (p>0.05). For the test of athletes' explosive power, five vertical jumps in situ were selected for testing, and the jump height and time in the air of each vertical jump were counted to calculate the maximum and average values of five vertical jumps. The results showed that there was no significant change in the explosive force of the athletes' lower limbs after training. The reason may be that strength training needs to follow the principles of heavy load, specialization, exercise sequence and reasonable interval. The intermittent training method used during training is not specialized in strength training, and the reasonable interval of strength training was not considered in the training process. CONCLUSIONS: Intermittent training can increase the tension of the cardiac vagus nerve of college basketball players, increase the cardiac reserve function and the load that the heart can bear, so that the cardiac function can be improved well. It can improve the cardiopulmonary function and aerobic work ability of college basketball players. It can improve the adjustment ability of the heart, lungs, liver, and other organs of college basketball players. It also can increase the load intensity that the central nerve can bear and improve the function of the central nerve and autonomic nerve. The anti-fatigue ability of athletes can be improved. It can improve the speed quality of college basketball players.

Significance of photodocumentation-associated factors in colonoscopy on the detection rate of colorectal neoplasms.

OBJECTIVE: It is unclear whether photodocumentation is associated with colorectal neoplasm (CRN) detection at colonoscopy, despite its ability to take more images with the development of affordable digital imaging systems. This study aimed to investigate whether photodocumentation-related factors could affect the detection rate of CRNs in healthy subjects. PATIENTS AND METHODS: A total of 2,637 subjects undergoing screening colonoscopy in routine health check-ups at CHA Bundang Medical from January to September 2016 were enrolled in this study. Only the endoscopic image data for observation purposes during colonoscopy withdrawal was used in this analysis. The number of observation images, observation time and the speed of photodocumentation (SPD) defined as the number of observation images per minute were used as quantity measures of photodocumentation. The presence of documented anatomical landmarks such as appendix orifice (AO), ileocecal valve (ICV), anorectal junction was used as quality measures of photodocumentation. RESULTS: Among subject-related factors, the independent factors for CRN detection in the multivariate analysis were age, male sex, waist circumference, and family history of colorectal cancer. In photo-documentation-related factors, SPD [Odds ratio (OR) 0.800; 95% confidence interval (CI), 0.740 to 0.864], observation time over 6 min (OR 1.671; 95% CI, 1.145 to 2.439), clear documentation of appendix orifice (AO) (OR 5.976; 95% CI, 4.548 to 7.852) and ileocecal valve (ICV) (OR 3.826; 95% CI, 2.985 to 4.904), and endoscopists (p < 0.001) were independently significant factors. However, the number of observation images was not associated with the detection of CRNs. CONCLUSIONS: Lower SPD and clear documentation of cecal landmarks might be associated with an increased detection rate of CRNs.

The Safety of Intra-arterial Tirofiban during Endovascular Therapy after Intravenous Thrombolysis.

BACKGROUND AND PURPOSE: The safety and efficacy of tirofiban during endovascular therapy in patients undergoing intravenous thrombolysis with recombinant IV tPA remain unclear. This study aimed to investigate the safety and efficacy of intra-arterial tirofiban use during endovascular therapy in patients treated with IV tPA. MATERIALS AND METHODS: Using a multicenter registry, we enrolled patients with acute ischemic stroke who underwent endovascular therapy. Safety outcomes included postprocedural parenchymal hematoma type 2 and/or thick subarachnoid hemorrhage, intraventricular hemorrhage, and 3-month mortality. Efficacy outcomes included the successful reperfusion rate, postprocedural reocclusion, and good outcomes at 3 months (mRS scores of 0-2). The tirofiban effect on the outcomes was evaluated using a multivariable analysis while adjusting for potential confounders. RESULTS: Among enrolled patients, we identified 314 patients with stroke (279 and 35 patients in the no tirofiban and tirofiban groups, respectively) due to an intracranial artery occlusion who underwent endovascular therapy with intravenous thrombolysis. A multivariable analysis revealed no association of intra-arterial tirofiban with postprocedural parenchymal hematoma type and/or thick subarachnoid hemorrhage (adjusted OR, 1.07; 95% CI, 0.20-4.10; P = .918), intraventricular hemorrhage (adjusted OR, 0.43; 95% CI, 0.02-2.85; P = .467), and 3-month mortality (adjusted OR, 0.38; 95% CI, 0.04-1.87; P = .299). Intra-arterial tirofiban was not associated with good outcome (adjusted OR, 2.22; 95% CI, 0.89 -6.12; P = .099). CONCLUSIONS: Using intra-arterial tirofiban during endovascular therapy after IV tPA could be safe.

Integrase strand transfer inhibitor treatment does not increase the incidence of immune reconstitution inflammatory syndrome in HIV-infected Koreans.

OBJECTIVES: Immune reconstitution inflammatory syndrome (IRIS) is a major concern when starting antiretroviral therapy (ART) in patients with advanced HIV infection. The aim of this study was to determine the incidence and risk factors of IRIS in HIV-infected Koreans initiating ART, and whether integrase strand transfer inhibitor (INSTI) treatment increases the risk of IRIS. METHODS: This retrospective analysis included adults living with HIV, seen at four university-affiliated hospitals in South Korea, who were naïve to ART and had a CD4 T-cell count < 200 cells/µL between January 2004 and May 2019. IRIS was determined through a medical record review within 6 months of ART initiation. Propensity score-matched case-control study between the non-INSTI and INSTI groups was performed. RESULTS: The study included 501 patients; 192 were assigned to the INSTI group, who started ART based on INSTIs as the initial treatment. There were opportunistic infections (OIs) in 253 (50.5%) cases before ART initiation. The three most common OIs were Pneumocystis jirovecii pneumonia, candidiasis and tuberculosis (TB). We identified 47 cases of IRIS; TB-IRIS was the most common type. The incidence of IRIS within 6 months of ART initiation was 9.4%, and there were no significant differences in baseline characteristics and incidence of IRIS between the matched groups. The risk factors for IRIS were pre-ART CD4 T-cell count (< 30 cells/µL), higher pre-ART viral load (≥ 75 000 copies/mL), and TB-OI. CONCLUSIONS: The incidence of IRIS was 9.4% in Korean HIV patients. The INSTI regimen was not related to IRIS occurrence.

Anatomy of the superior hypogastric plexus and its application in nerve-sparing paraaortic lymphadenectomy.

BACKGROUND: The purpose of this study was to clarify the anatomy of the superior hypogastric plexus, which would contribute to advancement of nerve-sparing paraaortic lymphadenectomy. MATERIALS AND METHODS: Eighteen cadavers were dissected and morphometrically analysed based on photographic images. Anatomical landmarks such as aortic bifurcation, transitional points of abdominal aorta to bilateral common iliac arteries, and cross point of the right ureter and pelvic brim, and cross point of sigmoid mesentery and pelvic brim were selected as reference points. RESULTS: The left lowest lumbar splanchnic nerve was located more laterally to transitional point of abdominal aorta to in 11/18 specimens, whereas the right lowest lumbar splanchnic nerve passed onto the right transitional point in only one specimen. The lowest lumbar splanchnic nerves or the superior hypogastric plexus covered the aortic bifurcation in 11/18 specimens. The superior hypogastric plexus was separate from the cross point of right ureter and pelvic brim as well as cross point of sigmoid mesentery and pelvic brim. CONCLUSIONS: The superior hypogastric plexus is at risk of injury during paraaortic lymphadenectomy because of its topography. Preservation of the superior hypogastric plexus regarding its anatomic basis during paraaortic lymphadenectomy is required.

Both cardiovascular and cerebrovascular events are decreased following long-term narrowband ultraviolet B phototherapy in patients with vitiligo: a propensity score matching analysis.

BACKGROUND: Systemic effects of long-term narrowband ultraviolet B (NB-UVB) phototherapy have not been well studied in vitiligo patients. An 11-year nationwide population-based retrospective cohort study was conducted using the Korean National Health Insurance claims database (2007-2017). OBJECTIVES: To investigate the effects of long-term NB-UVB phototherapy on the risk of cardiovascular and cerebrovascular events in vitiligo patients. METHODS: This study included vitiligo patients with ≥100 phototherapy sessions (phototherapy group, n = 3229) and <3 phototherapy sessions (no phototherapy group, n = 9687), in which covariables with age, sex, insurance type and comorbidities such as diabetes, hypertension and hyperlipidemia were matched by 1 : 3 propensity score matching. The outcomes of interest were cardiovascular (ischaemic heart disease and myocardial infarction) and cerebrovascular events (cerebrovascular infraction and haemorrhage). Cox proportional hazards models were used to assess the associations between NB-UVB phototherapy and each event. RESULTS: The risk of cardiovascular or cerebrovascular events was significantly decreased in the phototherapy group compared with the no phototherapy group [hazard ratio (HR) 0.637, 95% confidence interval (CI) 0.523-0.776]. Subgroup analysis revealed that the risk of cardiovascular (HR: 0.682, 95% CI: 0.495-0.940) and cerebrovascular events (HR: 0.601, 95% CI: 0.470-0.769) were significantly lower in the phototherapy group than the no phototherapy group, respectively. CONCLUSIONS: Our findings suggest that long-term NB-UVB phototherapy could decrease the risk of cardiovascular and cerebrovascular events in patients with vitiligo.

Bifidobacterium longum DS0956 and Lactobacillus rhamnosus DS0508 culture-supernatant ameliorate obesity by inducing thermogenesis in obese-mice.

Excessive body fat and the related dysmetabolic diseases affect both developed and developing countries. The aim of this study was to investigate the beneficial role of a bacterial culture supernatant (hereafter: BS) of Lactobacillus and Bifidobacterium and their potential mechanisms of action on white-fat browning and lipolysis. For selection of four candidates among 55 Lactic acid producing bacteria (LAB) from human infant faeces, we evaluated by Oil Red O staining and Ucp1 mRNA quantitation in 3T3-L1 preadipocytes. The expression of browning and lipolysis markers was examined along with in vitro assays. The possible mechanism was revealed by molecular and biological experiments including inhibitor and small interfering RNA (siRNA) assays. In a mouse model, physiological, histological, and biochemical parameters and expression of some thermogenesis-related genes were compared among six experimental groups fed a high-fat diet and one normal-diet control group. The results allow us to speculate that BS treatment promotes browning and lipolysis both in vitro and in vivo. Moreover, the BS may activate thermogenic programs via a mechanism involving PKA-CREB signaling in 3T3-L1 cells. According to our data, we can propose that two LAB strains, Bifidobacterium longum DS0956 and Lactobacillus rhamnosus DS0508, may be good candidates for a dietary supplement against obesity and metabolic diseases; however, further research is required for the development as dietary supplements or drugs.

Statin exposure and the risk of dementia in individuals with hypercholesterolaemia.

OBJECTIVES: This study aimed to examine the association between statin exposure and dementia risk in individuals with hypercholesterolaemia using data from the NHIS-HEALS database between 2002 and 2015. METHODS: Subjects were classified into statin exposure and statin nonexposure groups according to medication possession ratio. Dementia was defined as those with primary diagnostic dementia codes such as F00-F03, G30, G31.1, G31.9 or G31.82. Cox proportional hazards regression models were adopted after stepwise adjustment for confounders to investigate the prospective association between statin exposure and dementia risk. RESULTS: During the follow-up period (median follow-up 11.7 years), 711 cases of dementia occurred, accounting for 11.5% of the total study population (statin exposure group, 8.2%; statin nonexposure group, 12.9%). Compared to the statin nonexposure group, fully adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) for overall dementia in the statin exposure group were 0.63 (0.43-0.91) and 0.62 (0.50-0.78) in men and women, respectively. Compared to the statin nonexposure group, the HRs (95% CIs) for Alzheimer's disease and related dementia, vascular dementia and other types of dementia in the statin exposure group were 0.54 (0.32-0.91), 2.45 (0.69-8.68) and 0.59 (0.32-1.07), respectively, in men and 0.53 (0.38-0.73), 1.29 (0.42-3.96) and 0.70 (0.51-0.96), respectively, in women. CONCLUSIONS: Hypercholesterolaemic individuals exposed to statin had a lower risk of overall dementia and Alzheimer's disease and related dementia in both sexes, and a lower risk of other types of dementia in women, than subjects who were not exposed to statins.

Effect of Tack Cure on Polymerization Shrinkage of Resin-based Luting Cements.

CLINICAL RELEVANCE: Self-cure after tack cure could result in a lower polymerization shrinkage in some resin-based luting cements, which is closely related to lower degree of cure.

Chlorhexidine sensitivity in staphylococci isolated from patients with central line-associated bloodstream infection.

Since 2011, 2% chlorhexidine in 70% isopropyl alcohol (2% chlorhexidine tincture) has been widely used in Korea. To investigate changes in chlorhexidine sensitivity of staphylococci causing central line-associated bloodstream infections, 264 blood culture isolates from adult patients treated in intensive care units of five university hospitals between 2008 and 2016 were analysed. We observed no significant changes in chlorhexidine minimum inhibitory and bactericidal concentrations, or in the prevalence of resistance-associated genes before and after introduction of 2% chlorhexidine tincture. Thus, there was no evidence of increased resistance to chlorhexidine in staphylococci causing central line-associated bloodstream infections.

Effect of leg-length discrepancy following total hip arthroplasty on collapse of the contralateral hip in bilateral non-traumatic osteonecrosis of the femoral head.

AIMS: The purpose of this study was to examine whether leg-length discrepancy (LLD) following unilateral total hip arthroplasty (THA) affects the incidence of contralateral head collapse and subsequent THA in patients with bilateral osteonecrosis, and to determine factors associated with subsequent collapse. PATIENTS AND METHODS: We identified 121 patients with bilateral non-traumatic osteonecrosis who underwent THA between 2003 and 2011 to treat a symptomatic hip, and who also exhibited medium-to-large lesions (necrotic area ≥ 30%) in an otherwise asymptomatic non-operated hip. Of the 121 patients, 71 were male (59%) and 50 were female (41%), with a mean age of 51 years (19 to 71) at the time of initial THA. All patients were followed for at least five years and were assessed according to the presence of a LLD (non-LLD vs LLD group), as well as the LLD type (longer non-operated side vs shorter non-operated side group). RESULTS: Overall, 68 hips (56%) became painful and progressed to collapse at a mean of 2.6 years (0.2 to 13.8), resulting in 59 THAs (49%). The five-year collapse-free survival rate for the non-LLD group was 59% (95% confidence interval (CI) 46.8 to 71.8) compared with 45% (95% CI 32.9 to 57.5) for the LLD group (p = 0.036), and 66% (95% CI 55.2 to 77.2) for the longer non-operated side group compared with 32% (95% CI 19.1 to 44.9) for the shorter non-operated side group (p < 0.001). Multivariate regression analyses found that large lesions had a higher risk of collapse than medium-size lesions (odds ratio (OR) 4.19, 95% confidence interval (CI) 1.69 to 10.38; p = 0.002). Meanwhile, patients with a LLD < 3 mm (OR 0.20, 95% CI 0.08 to 0.52; p = 0.001) or a longer non-operated leg (OR 0.11, 95% CI 0.04 to 0.28; p < 0.001) after THA were less likely to experience a subsequent collapse. CONCLUSION: We found that LLD may be a modifiable risk factor for femoral head collapse. Minimizing LLD and particularly avoiding a shorter non-operated limb after THA may lead to a lower risk of collapse of the asymptomatic hip in patients with bilateral non-traumatic osteonecrosis. Cite this article: Bone Joint J 2019;101-B:303-310.

The effect of haemodynamic and peripheral vascular variability on cardiac output monitoring: thermodilution and non-invasive pulse contour cardiac output during cardiothoracic surgery.

While haemodynamic variability interferes with the assumption of constant flow underlying thermodilution cardiac output calculation, variability in (peripheral) arterial vascular physiology may affect pulse contour cardiac output methods. We compared non-invasive finger arterial pressure-derived continuous cardiac output measurements (Nexfin® ) with cardiac output measured using thermodilution during cardiothoracic surgery and determined the impact of cardiovascular variability on either method. We compared cardiac output derived from non-invasive finger arterial pressure with cardiac output measured by thermodilution at four grades (A-D) of cardiovascular variability. We defined Grade A data as heart rate and mean arterial pressure variability < 5% and the absence of arrhythmias (implying stable flow) and Physiocal® interval (as measure of variability in finger arterial physiology) > 30 beats. Grade B included all levels of heart rate/mean arterial pressure variability and arrhythmias (Physiocal < 30 excluded). Grade C included all Physiocal intervals (heart rate/mean arterial pressure variability > 5% and arrhythmias excluded). Grade D included all data. Comparison results were quantified as percentage errors. We analysed measurements in 27 patients undergoing coronary artery bypass surgery. Before extracorporeal circulation, the percentage error was 23% (n = 14 patients) in grade A, 28% (n = 20) in grade B, 32% (n = 22) in grade C and 37% (n = 26) in grade D, with a significant increase in variance (p = 0.035). Bias did not differ between grades. After extracorporeal circulation (n = 27), percentage errors became larger, but were not different between grades. Variability during cardiothoracic surgery affected the comparison between thermodilution and non-invasive finger arterial pressure-derived cardiac output. When the main sources of variability were included, percentage errors were large. Future cardiac output methodology comparison studies should report haemodynamic variability.

Proliferation of prostate epithelia induced by IL-6 from stroma reacted with Trichomonas vaginalis.

Benign prostatic hyperplasia (BPH) is characterized by the proliferation of stromal and epithelial cell types in the prostate, and interactions between the two types of cells. We demonstrated previously that proliferation of prostate stromal cells was induced by BPH epithelial cells in response to Trichomonas vaginalis (Tv) infection via crosstalk with mast cells. In this study, we investigated whether IL-6 released by the proliferating stromal cells in turn induce the BPH epithelial cells to multiply. When culture supernatants of the proliferating prostate stromal cells were added to BPH epithelial cells, the latter multiplied, and expression of cyclin D1, FGF2 and Bcl-2 increased. Blocking the IL-6 signalling pathway with anti-IL-6R antibody or JAK1/2 inhibitor inhibited the proliferation of the BPH epithelial cells and reduced the expression of IL-6, IL-6R and STAT3. Also, epithelial-mesenchymal transition was detected in the proliferating BPH epithelial cells. In conclusion, IL-6 released from proliferating prostate stromal cells induced by BPH epithelial cells infected with Tv in turn induces multiplication of the BPH epithelial cells. This result provides first evidence that the inflammatory microenvironment of prostate stromal cells resulting from Tv infection induces the proliferation of prostate epithelial cells by stromal-epithelial interaction.

Evaluation of Quality of Life Outcomes Following Palliative Treatment of Bone Metastases with Magnetic Resonance-guided High Intensity Focused Ultrasound: An International Multicentre Study.

AIMS: To determine quality of life (QoL) outcomes after palliation of pain from bone metastases using magnetic resonance-guided high intensity focused ultrasound (MR-guided HIFU), measured using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C15-PAL and the QLQ-BM22 questionnaires. MATERIALS AND METHODS: Twenty patients undergoing MR-guided HIFU in an international multicentre trial self-completed the QLQ-C15-PAL and QLQ-BM22 questionnaires before and on days 7, 14, 30, 60 and 90 post-treatment. Descriptive statistics were used to represent changes in symptom and functional scales over time and to determine their clinical significance. QoL changes were compared in pain responders and non-responders (who were classified according to change in worst pain score and analgesic intake, between baseline and day 30). RESULTS: Eighteen patients had analysable QoL data. Clinically significant improvements were seen in the QoL scales of physical functioning, fatigue, appetite loss, nausea and vomiting, constipation and pain in the 53% of patients who were classified as responders at day 30. No significant changes were seen in the 47% of patients who were non-responders at this time point. CONCLUSION: Local treatment of pain from bone metastases with MR-guided HIFU, even in the presence of disseminated malignancy, has a substantial positive effect on physical functioning, and improves other symptomatic QoL measures. This indicated a greater response to treatment over and above pain control alone. MR-guided HIFU is non-invasive and should be considered for patients with localised metastatic bone pain and poor QoL.

Comparative outcomes of cefazolin versus nafcillin for methicillin-susceptible Staphylococcus aureus bacteraemia: a prospective multicentre cohort study in Korea.

OBJECTIVES: No randomized controlled trials have evaluated the comparative outcomes of cefazolin versus nafcillin for methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia. METHODS: A prospective observational cohort study including all S. aureus bacteraemia was conducted at 10 hospitals. Patients (≥15 years) with MSSA bacteraemia who received cefazolin or nafcillin as definitive antibiotics were included. The rates of treatment failure (premature discontinuation of antibiotics because of adverse effects, switching of antibiotics because of clinical failure, all-cause mortality within 1 month, or recurrence) were compared between the cefazolin and nafcillin groups. Propensity score matching analyses were performed to balance the factors influencing the selection of antibiotics. RESULTS: Among the 242 included cases, the bones and joints (36.8%) were the most common sites of infection and 60.7% of the patients had sepsis. The overall treatment failure rate was 43.8% (106/242). All-cause mortality within 1 month was 6.2% (15/242). After propensity score matching, the treatment failure rate of cefazolin was lower than that of nafcillin (30.4% (24/79) vs. 49.4% (39/79), p 0.015) because of a higher rate of discontinuation caused by adverse events. When the data were limited to patients with sepsis, the treatment failure rates of both groups were not significantly different. Approximately 22% (24/110) of MSSA isolates exhibited a cefazolin-inoculum effect (CIE) that had significant impact on the failure rate and mortality of the cefazolin group. CONCLUSIONS: Cefazolin might be recommended as an adequate and better-tolerated treatment for MSSA bacteraemia in the absence of CIE.

agr functionality affects clinical outcomes in patients with persistent methicillin-resistant Staphylococcus aureus bacteraemia.

Methicillin-resistant Staphylococcus aureus bacteremia (MRSAB) often persists despite appropriate antibiotic therapy. It is unclear what microbiological factors contribute to poor clinical outcomes in persistent MRSAB (pMRSAB). We aimed to identify clinical and microbiological risk factors for in-hospital mortality in pMRSAB. We analysed MRSAB cases prospectively collected between 2009 and 2016 at 11 hospitals in Korea, defining cases of pMRSAB as MRSAB lasting ≥5 days despite administration of effective antibiotics. The first blood isolates from the pMRSAB cases were tested for staphylococcal cassette chromosome mec type, staphylococcal protein A type, accessary gene regulator (agr) type, genes for Panton-Valentine leukocidin and phenol-soluble modulin-mec, vancomycin minimum inhibitory concentration, vancomycin heteroresistance, and agr functionality. We also collected clinical information for each case. Of 960 MRSAB cases, 152 pMRSAB were finally eligible. Univariable analysis revealed that in-hospital mortality was significantly associated with Charlson's comorbidity-weighted index (CCWI) score, Pitt bacteremia score, sequential organ failure assessment score, presentation with septic shock, pneumonia, agr dysfunction, and vancomycin heteroresistance. Bone and joint infections were negatively associated with in-hospital mortality. Multivariable analysis revealed the following independent risk factors for in-hospital mortality: CCWI score [adjusted odds ratio (aOR), per one point, 1.25; 95% confidence interval (CI), 1.08-1.44; P = 0.003), Pitt bacteremia score (aOR, per one point, 1.33; 95% CI, 1.09-1.62; P = 0.005), non-eradicated foci of infection (aOR, 3.12; 95% CI, 1.18-8.27; P = 0.022), and agr dysfunction (aOR, 2.48; 95% CI, 1.12-5.47; P = 0.025). agr dysfunction is an independent risk factor for in-hospital mortality in pMRSAB.

Progression of Osteoporosis After Kidney Transplantation in Patients With End-Stage Renal Disease.

BACKGROUND: This study investigated the prevalence of osteoporosis and the risk factors for its progression in kidney transplant recipients (KTRs). METHODS: Dual energy X-ray absorptiometry was used to prospectively measure changes in bone mineral density (BMD) before kidney transplantation (KT) and 1 year after transplantation in 207 individuals. We also analyzed the risk factors of osteoporosis progression during this period. RESULTS: Prior to KT, the mean BMD score (T-score of the femur neck area) was -2.1 ± 1.2, and the prevalence of osteoporosis was 41.5% (86/207). At 1 year post-transplantation, the mean BMD score significantly decreased to -2.3 ± 1.1 (P < .001), and the prevalence of osteoporosis increased to 47.3% (98/207; P = .277). The BMD score worsened over the study period in 69.1% (143/207) of patients, improved in 24.1% (50/207), and showed no change in 6.8% (14/207). Minimal intact parathyroid hormone (iPTH) improvement after KT was found to be an independent risk factor of osteoporosis progression. CONCLUSIONS: This study demonstrates progressive loss of BMD after KT and sustained secondary hyperparathyroidism might influence the progression of osteoporosis.

A Case of Ectopic Paragonimiasis in a 17th Century Korean Mummy.

Archaeoparasitological studies on fossilized feces obtained from Joseon Dynasty (1392-1910 CE) mummies have provided invaluable data on the patterns of parasitic infection in pre-modern Korean societies. In our recent radiological investigation of a 17th century Joseon mummy discovered in Cheongdo (South Korea), we located a liver mass just below the diaphragm. Anatomical dissection confirmed the presence of a mass of unknown etiology. A subsequent parasitological examination of a sample of the mass revealed a large number of ancient Paragonimus sp. eggs, making the current report the first archaeoparasitological case of liver abscess caused by ectopic paragonimiasis.