Vancomycin is the most frequently used antibiotic, accounting for up to 35% of hospitalized patients with infection, because of its optimal bactericidal effectiveness and relatively low price. ...Vancomycin-associated AKI (VA-AKI) is a clinically relevant but not yet clearly understood entity in critically ill patients. The current review comprehensively summarizes the pathophysiological mechanisms of, biomarkers for, preventive strategies for, and some crucial issues with VA-AKI. The pathological manifestations of VA-AKI include acute tubular necrosis, acute tubulointerstitial nephritis (ATIN), and intratubular crystal obstruction. The proposed pathological mechanisms of VA-AKI include oxidative stress and allergic reactions induced by vancomycin and vancomycin-associated tubular casts. Concomitant administration with other nephrotoxic antibiotics, such as piperacillin-tazobactam, high vancomycin doses, and intermittent infusion strategies compared to the continuous infusion are associated with a higher risk of VA-AKI. Several biomarkers could be applied to predict and diagnose VA-AKI. To date, no promising therapy is available. Oral steroids could be considered for patients with ATIN, whereas hemodialysis might be applied to remove vancomycin from the patient. In the future, disclosing more promising biomarkers that could precisely identify populations susceptible to VA-AKI and detect VA-AKI occurrence early on, and developing pharmacological agents that could prevent or treat VA-AKI, are the keys to improve the prognoses of patients with severe infection who probably need vancomycin therapy.
Intratumoural hypoxia induces HIF-1α and promotes tumour progression, metastasis and treatment resistance. HIF-1α stability is regulated by VHL-E3 ligase-mediated ubiquitin-dependent degradation; ...however, the hypoxia-regulated deubiquitinase that stabilizes HIF-1α has not been identified. Here we report that HAUSP (USP7) deubiquitinase deubiquitinates HIF-1α to increase its stability, induce epithelial-mesenchymal transition and promote metastasis. Hypoxia induces K63-linked polyubiquitinated HAUSP at lysine 443 to enhance its functions. Knockdown of HAUSP decreases acetylation of histone 3 lysine 56 (H3K56Ac). K63-polyubiquitinated HAUSP interacts with a ubiquitin receptor CBP to specifically mediate H3K56 acetylation. ChIP-seq analysis of HAUSP and HIF-1α binding reveals two motifs responsive to hypoxia. HectH9 is the E3 ligase for HAUSP and a prognostic marker together with HIF-1α. This report demonstrates that hypoxia-induced K63-polyubiquitinated HAUSP deubiquitinates HIF-1α and causes CBP-mediated H3K56 acetylation on HIF-1α target gene promoters to promote EMT/metastasis, further defining HAUSP as a therapeutic target in hypoxia-induced tumour progression.
Short sleep duration has been found to be associated with bone health deterioration by using bone mineral density (BMD). Only a few attempts have been made to assess the association of sleep duration ...and bone by utilizing the trabecular bone score (TBS). The aim of this study was to examine the association between sleep duration and TBS from a national database. A total of 4480 eligible participants older than 20 years who attended the United States National Health and Nutrition Examination Survey (NHANES) from 2005 to 2006 with TBS data and self-reported sleep duration. The association between sleep duration and TBS was investigated using a multivariate regression model with covariate adjustment. TBS was lowest in individuals with a short sleep duration (≤ 5 h) and it was increased in those with longer self-reported total sleep times. After a full adjustment for covariates, those sleeping less than 5 h had a significantly lower TBS than the reference group (sleep duration of 7 h). In subgroup analyses, an association between short sleep duration (≤ 5 h) and lower TBS persisted in older ages (≥ 60 years old), women, obese adults (BMI ≥ 30 kg/m
), and non-Hispanic Whites. Short sleep duration is associated with low TBS in women, obese adults (BMI ≥ 30 kg/m
), and non-Hispanic whites. Strict self-monitoring of body weight, well-tailored controls of underlying disease(s), and adequate sleep may help prevent osteoporosis.
Summary
Background
The pathogenesis of gastro‐oesophageal reflux disease (GERD) is complex and multifactorial. The oesophageal hypervigilance and anxiety scale (EHAS) is a novel cognitive‐affective ...evaluation of visceral sensitivity.
Aims
To investigate the interrelationship between EHAS and reflux symptom severity, psychological stress, acid reflux burden, phenotypes, and oesophageal mucosal integrity in patients with GERD.
Methods
Patients with chronic reflux symptoms and negative endoscopy underwent 24‐hour impedance‐pH monitoring for phenotyping, acid reflux burden, and mucosal integrity with mean nocturnal baseline impedance (MNBI) calculation. Validated scores for patient‐reported outcomes, including EHAS, GERD questionnaire (GERDQ), State‐Trait Anxiety Inventory score, and Taiwanese Depression Questionnaire score, were recorded.
Results
We enrolled 105 patients, aged 21‐64 years (mean, 48.8), of whom 58.1% were female; 27 had non‐erosive reflux disease, 43 had reflux hypersensitivity and 35 had functional heartburn. There were no significant differences in sex, EHAS, GERDQ, questionnaires of depression or anxiety among GERD phenotypes. EHAS was significantly correlated with GERDQ, questionnaires of depression and anxiety (P < 0.05). However, there were no significant correlations between GERDQ and questionnaires of depression or anxiety. Regarding patient‐reported outcomes, GERDQ positively correlated with acid exposure time and negatively correlated with MNBI (P < 0.05).
Conclusions
EHAS associates with reflux symptom severity and psychological stress but not with acid reflux burden or mucosal integrity. Thus, EHAS assessment shows promise in assessment of subjective patient outcome and satisfaction with treatment, a hitherto unmet clinical need.
The putative modulators for reflux symptom severity.
Laparoscopic gastric bypass (GB) is reportedly more effective than laparoscopic sleeve gastrectomy (SG) in the treatment of patients with a low body mass index and type 2 diabetes mellitus. However, ...the mechanism remains speculative. We compared the postprandial gut hormone patterns between patients undergoing laparoscopic GB and laparoscopic SG at 2 years after surgery in a hospital-based, prospective study.
A total of 16 laparoscopic GB and 16 laparoscopic SG patients were followed up and appraised for glucose homeostasis. Two years after surgery, the mixed meal test and gut hormones were evaluated in 13 laparoscopic GB and 13 laparoscopic SG patients who had been included in the previous randomized trial.
The preoperative characteristics, such as body mass index, body weight, waist circumference, and duration of T2DM were comparable between the 2 groups. T2DM remission was achieved in 13 (81%) laparoscopic GB and 3 (19%) laparoscopic SG patients (P < .05) 2 years after surgery. The laparoscopic GB patients had lost more weight and had a smaller waist circumference and lower levels of glucose and hemoglobin A1c, and lower insulin resistance than the SG patients. Significant differences were found in acyl ghrelin, des-acyl ghrelin, cholecystokinin, and resistin between the 2 groups, but none in obestatin, gastric inhibitory peptide, glucagon-like peptide-1, and leptin.
Both laparoscopic GB and laparoscopic SG have strong hindgut effects after surgery, but GB has a significant duodenal exclusion effect on cholecystokinin. The laparoscopic SG group had lower acyl ghrelin and des-acyl ghrelin levels but greater concentrations of resistin than the laparoscopic GB group.
Background
Laparoscopic Roux-en-Y gastric bypass (LRYGB) is considered the gold standard for the treatment of morbid obesity but is technically challenging and results in significant perioperative ...complications. While laparoscopic mini-gastric bypass (LMGB) has been reported to be a simple and effective treatment for morbid obesity, controversy exists. Long-term follow-up data from a large number of patients comparing LMGB to LRYGB are lacking.
Methods
Between October 2001 and September 2010, 1,657 patients who received gastric bypass surgery (1,163 for LMGB and 494 for LRYGB) for their morbid obesity were recruited from our comprehensive obesity surgery center. Patients who received revision surgeries were excluded. Minimum follow-up was 1 year (mean 5.6 years, from 1 to 10 years). The operative time, estimated blood loss, length of hospital stay, and operative complications were assessed. Late complication, changes in body weight loss, BMI, quality of life, and comorbidities were determined at follow-up. Changes in quality of life were assessed using the Gastrointestinal Quality of Life Index.
Results
There was no difference in preoperative clinical parameters between the two groups. Surgical time was significantly longer for LRYGB (159.2 vs. 115.3 min for LMGB,
p
< 0.001). The major complication rate was borderline higher for LRYGB (3.2 vs. 1.8 %,
p
= 0.07). At 5 years after surgery, the mean BMI was lower in LMGB than LRYGB (27.7 vs. 29.2,
p
< 0.05) and LMGB also had a higher excess weight loss than LRYGB (72.9 vs. 60.1 %,
p
< 0.05). Postoperative gastrointestinal quality of life increased significantly after operation in both groups without any significant difference at 5 years. Obesity-related clinical parameters improved in both groups without significant difference, but LMGB had a lower hemoglobin level than LRYGB. Late revision rate was similar between LRYGB and LMGB (3.6 vs. 2.8 %,
p
= 0.385).
Conclusions
This study demonstrates that LMGBP can be regarded as a simpler and safer alternative to LRYGB with similar efficacy at a 10-year experience.
The performance of hybrid perovskite‐based light‐emitting diodes (LEDs) is markedly enhanced by the application of a NiOx electrode interlayer and moderate methylamine treatment. A hybrid ...perovskite‐based LED exhibits a peak luminous efficiency of 15.9 cd A−1 biased at 8.5 V, 407.65 mA cm−2, and 65 300 cd m−2, showing a distinctive impact for future applications.
Procalcitonin (PCT) has garnered attention as a potential diagnostic biomarker for infection in cancer patients. We performed a systematic review and meta-analysis to evaluate the diagnostic accuracy ...of procalcitonin (PCT) and to compare it with C-reactive protein (CRP) in adult non-neutropenic cancer patients with suspected infection.
A systematic literature search was performed in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials to identify all relevant diagnostic accuracy studies. Original articles reporting the diagnostic accuracy of PCT for infection detection in adult patients with solid or hematological malignancies were included. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, area under the hierarchical summary receiver operator characteristic (HSROC) curve, and corresponding 95% confidence interval (CI) were calculated.
Seven studies were included in the meta-analysis. The pooled sensitivity and specificity of PCT were 60% (95% CI 45-74%) and 78% (95% CI 69-86%). The diagnostic odds ratio was estimated at 5.47 (95% CI 2.86-10.46). Three studies compared the diagnostic accuracies of PCT and CRP. The pooled sensitivity and specificity values for PCT were 57% (95% CI 26-83%) and 75% (95% CI 68-82%), and those for CRP were 67% (95% CI 35-88%) and 73% (95% CI 69-77%). The pooled sensitivity and specificity of PCT and CRP did not differ significantly (p = 0.61 and p = 0.63). The diagnostic accuracy of PCT was similar to that of CRP as measured by the area under the HSROC curve (0.73, CI = 0.61-0.91 vs. 0.74, CI = 0.61-0.95, p = 0.93).
While elevated PCT levels can be indicative of potential infection, they should not be solely relied upon to exclude infection. We recommend not using the PCT test in isolation; Instead, it should be carefully interpreted in the context of clinical findings.
Studies into the association between hypertensive disorders during pregnancy and end-stage renal disease are limited. We investigated the risk of end-stage renal disease after delivery among women ...with hypertensive disorders during pregnancy.
We used insurance claims data from 1998 to 2009 to identify 26,651 women aged 19-40 years old who experienced hypertensive disorders during pregnancy; these women had no history of hypertension, diabetes, kidney disease or lupus. We also randomly selected 213,397 women without hypertensive disorders during pregnancy as a comparison cohort; the frequency was matched by age and index year of pregnancy. We compared the incidence of end-stage renal disease in the 2 cohorts. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) after controlling for demographic and clinical factors.
Women with hypertensive disorders during pregnancy had a greater risk of chronic kidney disease and end-stage renal disease, with adjusted HRs of 9.38 (95% CI 7.09-12.4) and 12.4 (95% CI 8.54-18.0), respectively, after controlling for urban status, coronary artery disease, congestive heart failure, hyperlipidemia and abruption. The HR for end-stage renal disease was 2.72 (95% CI 1.76-4.22) after we also controlled for hypertension and diabetes. Women with preeclampsia or eclampsia had a higher risk of end-stage renal disease (adjusted HR 14.0, 95% CI 9.43-20.7) than women who had gestational hypertension only (adjusted HR 9.03, 95% CI 5.20-15.7).
Women with hypertensive disorders during pregnancy were at a high risk of end-stage renal disease. The risk was much greater for women who had preeclampsia or eclampsia than those who had gestational hypertension only.
It has been unclear whether diabetes mellitus (DM) is positively associated with a risk of venous thromboembolism (VTE). In addition, whether the risk of VTE is altered in patients with type 1 ...diabetes (T1DM) has rarely been explored.
We investigated whether patients with T1DM are at a relatively high risk of VTE development.
We retrieved data from the National Health Insurance Research Database of Taiwan to conduct this retrospective cohort study. The T1DM group consisted of 4967 patients diagnosed as having T1DM before 2003. The non-T1DM group comprised 19 868 age- and sex-matched enrollees without T1DM. Cox proportional hazard regression analysis was used to investigate the hazard ratio of VTE in patients with T1DM relative to those without T1DM.
During a mean follow-up period of 8.61 years, the risk of VTE in the T1DM group was 5.33-fold higher than in the non-T1DM group after adjusting for dyslipidemia, hypertension, stroke, lower leg fracture or surgery, and obesity. Further stratified analysis revealed that the risk of VTE was significantly high in both sexes and in all age groups below the age of 60.
T1DM appears to be an independent risk factor for VTE development.
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