Summary
The risk factors for atypical femur fracture in patients exposed to bisphosphonates for at least 1 year were examined. Prolonged and continuous use of bisphosphonates, long-term use of ...glucocorticoids, and a higher body mass index were associated with increased risk of atypical femur fracture.
Introduction
The purpose of the present study is to determine whether rheumatoid arthritis (RA) and other clinical factors are associated with an increased risk of bisphosphonate (BP)-related atypical femur fracture (AFF).
Methods
A retrospective nested case-control study of patients who had taken BPs for at least 1 year was conducted. Patients with AFF were identified by reviewing surgical and radiographic records. Three controls with no history of AFFs were randomly selected and age- and sex-matched to each patient with AFFs. Cox proportional hazard models were used to analyze the independent contribution of risk factors to BP-related AFF.
Results
Among the 35,104 patients prescribed BPs for at least 1 year, 43 females (mean age, 68 years) suffered AFFs (0.12%). Patients with AFFs were exposed to BPs for a mean of 7.3 years. Patients with AFFs were exposed to BPs for longer than those without AFFs and continued treatment without a drug holiday. More patients with AFF than controls had taken glucocorticoids and disease-modifying anti-rheumatic drugs. Multivariate Cox regression analyses estimated that long-term use of glucocorticoids, prolonged exposure to BP without cessation, and every 1 kg/m
2
increase in the body mass index (BMI) increased the hazard ratio for AFFs by 3.0, 5.2, and 1.2, respectively.
Conclusions
Prolonged and continuous use of BPs, long-term use of glucocorticoids, and a higher BMI increase the risk of AFFs. Switching long-term BP and glucocorticoid users to other bone-protective agents should be considered.
Objective: The aim was to investigate the white matter abnormalities of drug‐naïve patients with obsessive–compulsive disorder (OCD) using diffusion tensor‐imaging and the white matter changes in ...the patients after pharmacotherapy.
Method: Thirteen drug‐naïve OCD patients and 13 age‐ and sex‐matched healthy comparison subjects were examined using diffusion tensor‐imaging and structural magnetic resonance imaging. Measurements were made in OCD patients before and after 12 weeks of citalopram treatment.
Results: Compared with controls, the drug‐naïve OCD patients showed significant increases in fractional anisotropy (FA) in the corpus callosum, the internal capsule and white matter in the area superolateral to the right caudate. The increases in FA were mostly no longer observed in patients after 12 weeks of treatment compared with controls.
Conclusion: Our findings suggest that white matter alterations are associated with the pathophysiology of OCD, and the abnormalities may be partly reversible with pharmacotherapy.
An open-label, randomized trial was conducted to examine the effects of risedronate versus menopausal hormone therapy (MHT) in postmenopausal women with recent hip fracture.
Among 1165 eligible ...women, 281 were recruited and randomly assigned to receive oral risedronate (35 mg/week) or percutaneous estradiol gel (1.5 mg/day) plus oral micronized progesterone (100 mg/day) for 4 years. The primary end point was recurrent fracture and the secondary end points were mortality and bone mineral density (BMD).
Kaplan-Meier analyses showed no significant differences in fracture recurrence and mortality between the two groups. The incidence of any new fracture per 100 person-years (PY) was 8.63 in the risedronate group and 12.86 in the MHT group (p = 0.180); that of clinical fracture was 4.75 and 6.99, respectively (p = 0.265); and that of asymptomatic vertebral fracture was 4.87 and 5.58, respectively (p = 0.764). The respective incidence of death per 100 PY was 3.58 and 4.40 (p = 0.503). BMD increased comparably at the lumbar spine in both groups. BMD at the total hip did not change in the risedronate group, but increased significantly by 2.8% in the MHT group.
MHT might not differ from risedronate in the prevention of secondary fractures and death among postmenopausal women with recent hip fracture.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
An analysis of atmospheric neutrino data from all four run periods of Super-Kamiokande optimized for sensitivity to the neutrino mass hierarchy is presented. Confidence intervals for Δm322, sin2θ23, ...sin2θ13 and δCP are presented for normal neutrino mass hierarchy and inverted neutrino mass hierarchy hypotheses, based on atmospheric neutrino data alone. Additional constraints from reactor data on θ13 and from published binned T2K data on muon neutrino disappearance and electron neutrino appearance are added to the atmospheric neutrino fit to give enhanced constraints on the above parameters. Over the range of parameters allowed at 90% confidence level, the normal mass hierarchy is favored by between 91.9% and 94.5% based on the combined Super-Kamiokande plus T2K result.
Summary
Polymorphonuclear (PMN) leucocytes participate in acute inflammatory pathologies such as acute respiratory distress syndrome (ARDS) following traumatic injury and shock, which also activates ...the coagulation system systemically. Trauma can prime the PMN nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex for an enhanced respiratory burst, but the relative role of various priming agents in this process remains incompletely understood. We therefore set out to identify mediators of PMN priming during coagulation and trauma‐shock and determine whether PMN reactive oxygen species (ROS) generated in this manner could influence organ injury and coagulation. Initial experiments demonstrated that PMN are primed for predominantly extracellular ROS production by products of coagulation, which was abrogated by CD88/C5a receptor(C5aR) inhibition. The importance of this was highlighted further by demonstrating that known PMN priming agents result in fractionally different amounts of extracellular versus intracellular ROS release depending on the agent used. Plasma from trauma patients in haemodynamic shock (n = 10) also primed PMN for extracellular ROS in a C5a‐dependent manner, which correlated with both complement alternative pathway activation and thrombin generation. Furthermore, PMN primed by preincubation with products of blood coagulation directly caused loss of endothelial barrier function in vitro that was abrogated by C5aR blockade or NADPH oxidase inhibition. Finally, we show in a murine model of trauma‐shock that p47phox knock‐out (KO) mice with PMN incapable of generating ROS were protected from inflammatory end‐organ injury and activated protein C‐mediated coagulopathy. In summary, we demonstrate that trauma‐shock and coagulation primes PMN for predominantly extracellular ROS production in a C5a‐dependent manner that contributes to endothelial barrier loss and organ injury, and potentially enhances traumatic coagulopathy.
Neutrophils (PMN) participate in acute inflammatory pathologies, such as ARDS following traumatic injury and shock, which also systemically activates the coagulation system. Trauma can prime the PMN NADPH oxidase complex for an enhanced respiratory burst, but the relative role of various priming agents in this process remains incompletely understood. We demonstrate that trauma‐shock and coagulation primes PMNs for predominantly extracellular ROS production in a C5a‐dependent manner that contributes to endothelial barrier loss and organ injury, and potentially enhances traumatic coagulopathy.
BACKGROUND AND PURPOSEThe 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 METHODSUsing 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. RESULTSAmong 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). CONCLUSIONSUsing intra-arterial tirofiban during endovascular therapy after IV tPA could be safe.
Abstract Background and aim Adipocyte fatty acid-binding protein (FABP4) is abundantly expressed in adipocytes and plays a role in glucose homeostasis. We analysed the relationship between serum ...FABP4 levels and the progression of metabolic syndrome in healthy adults. Methodsand results A total of 465 subjects were selected from participants in a medical check-up programme at a Health Promotion Center. Baseline serum FABP4 levels were measured, and the subjects were evaluated for the presence of metabolic syndrome (MetS) according to the recommendations of the American Heart Association/National Heart, Lung, and Blood Institute. The subjects were re-evaluated 4 years later. Baseline FABP4 concentrations were significantly higher in subjects with MetS than in those without MetS ( P < 0.001). At the 4-year follow-up, subjects in the highest FABP4 tertile at baseline exhibited higher values for body mass index, fat mass and percent body fat, as well as blood pressure, fasting glucose, total cholesterol, triglycerides, low-density lipoprotein (LDL)-cholesterol, insulin, homeostasis model assessment of insulin resistance, monocyte chemoattractant protein-1 and tumor necrosis factor-α levels (all P < 0.05). The subjects with higher FABP4 levels had lower HDL-cholesterol concentrations ( P < 0.05). After adjustment for age, sex, change in percent body fat and baseline values for other metabolic and inflammatory parameters, FABP4 levels at baseline were shown to be strongly associated with the development of MetS by year 4 (odds ratio (OR), 5.75; 95% confidence interval (CI), 2.71–12.23 for highest tertile vs. lowest tertile, P < 0.001) Conclusion Baseline serum FABP4 levels appear to be a significant predictor for the future development of MetS, independent of pro-inflammatory cytokines.
There remain concerns about the safety and functional benefit of laparoscopic pylorus-preserving gastrectomy (LPPG) compared with laparoscopic distal gastrectomy (LDG). This study evaluated ...short-term outcomes of a randomized clinical trial (RCT) comparing LPPG with LDG for gastric cancer.
The Korean Laparoendoscopic Gastrointestinal Surgery Study (KLASS)-04 trial was an investigator-initiated, open-label, parallel-assigned, superiority, multicentre RCT in Korea. Patients with cT1N0M0 cancer located in the middle third of the stomach at least 5 cm from the pylorus were randomized to undergo LPPG or LDG. Participants, care givers and those assessing the outcomes were not blinded to group assignment. Outcomes were 30-day postoperative morbidity rate and death at 90 days.
Some 256 patients from nine institutions were randomized (LPPG 129 patients, LDG 127 patients) between July 2015 and July 2017 and outcomes for 253 patients were analysed. Postoperative complications within 30 days were seen in 19.3 and 15.5 per cent in the LPPG and LDG groups respectively (P = 0·419). Postoperative pyloric stenosis was observed in nine (7.2 per cent) and two (1·5 per cent) patients in the LPPG and LDG groups (P = 0·026) respectively. In multivariable analysis higher BMI was a risk factor for postoperative complications (odds ratio 1·17, 95 per cent c.i. 1·04 to 1·32; P = 0·011). Death at 90 days was zero in both groups.
Postoperative complications and mortality was comparable in patients undergoing LPPG and LDG. Registration number: NCT02595086 (http://www.clinicaltrials.gov).
Endoscopic mucosal resection (EMR) is currently not accepted as an alternative treatment to surgery in early gastric cancer (EGC) of the undifferentiated histologic type. The present retrospective ...analysis examined the correlation of various histologic factors with the presence of lymph node metastasis (LNM).
A retrospective analysis on 234 patients with poorly differentiated EGC who underwent radical gastrectomy with D2 lymph node dissection was undertaken. Several clinicopathologic factors were investigated to identify predictive factors for LNM: age, sex, type of operation, tumor location, tumor size, gross type, ulceration, lymphatic invasion, and depth of invasion.
Of the 234 lesions with poorly differentiated EGC, half (n = 116) already showed submucosal invasion in the resection specimen; 25.9 % of those (30/116) were limited to the upper third (SM1). Of the lesions confined to the mucosa, LNM was found in 3.4 % (4/118). With minor submucosal infiltration (SM1), the LNM rate was lower (0/30) in our patient population. Only with SM2/3 infiltration did the LNM rate sharply rise to around 30 %. The cut-off for submucosal infiltration depth was 500 microm (0/32 LNM), above which LNM rates were substantial (31.2 %; 24/77). There was limited correlation between the SM1-3 classification and actual measurement of submucosal infiltration depth. In a multivariate analysis, tumor size ( P = 0.033), depth of invasion ( P = 0.004), and lymphatic invasion ( P < 0.001) were associated with LNM.
Poorly differentiated EGC confined to the mucosa or with minimal submucosal infiltration (<or= 500 microm) could be considered for curative EMR due to the low risk of LNM. Given the limited case number of subgroups, these findings should be confirmed by more data from other centers, which should also focus on local recurrence after EMR in poorly differentiated EGC.
Background
The aim of this study was to compare the results of laparoscopy‐assisted total gastrectomy with those of open total gastrectomy for early gastric cancer.
Methods
Patients with gastric ...cancer who underwent total gastrectomy with curative intent in three Korean tertiary hospitals between January 2003 and December 2010 were included in this multicentre, retrospective, propensity score‐matched cohort study. Cox proportional hazards regression models were used to evaluate the association between operation method and survival.
Results
A total of 753 patients with early gastric cancer were included in the study. There were no significant differences in the matched cohort for overall survival (hazard ratio (HR) for laparoscopy‐assisted versus open total gastrectomy 0·96, 95 per cent c.i. 0·57 to 1·65) or recurrence‐free survival (HR 2·20, 0·51 to 9·52). The patterns of recurrence were no different between the two groups. The severity of complications, according to the Clavien–Dindo classification, was similar in both groups. The most common complications were anastomosis‐related in the laparoscopy‐assisted group (8·0 per cent versus 4·2 per cent in the open group; P = 0·015) and wound‐related in the open group (1·6 versus 5·6 per cent respectively; P = 0·003). Postoperative death was more common in the laparoscopy‐assisted group (1·6 versus 0·2 per cent; P = 0·045).
Conclusion
Laparoscopy‐assisted total gastrectomy for early gastric cancer is feasible in terms of long‐term results, including survival and recurrence. However, a higher postoperative mortality rate and an increased risk of anastomotic leakage after laparoscopic‐assisted total gastrectomy are of concern.
Feasible but high risk of anastomotic complication
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