Risk of Incident Atrial Fibrillation With Zoledronic Acid Versus Denosumab: A Propensity Score–Matched Cohort Study

Zoledronic acid (ZA) is an effective agent in osteoporosis and malignancy-related bone disease but may be associated with increased risk of atrial fibrillation (AF), although current studies disagree on this risk. To examine the risk of incident AF among patients receiving ZA compared with denosumab in the first year of treatment, we performed a new-user, active comparator cohort study including privately insured Americans between January 1, 2010, and June 30, 2019. Individuals aged ≥50 years without known arrhythmia or advanced kidney disease who initiated ZA were 1:1 propensity score (PS)-matched to individuals initiating denosumab in separate osteoporosis and malignancy cohorts. The primary outcome was incident diagnosis of AF (≥ 1 inpatient or ≥ 2 outpatient diagnostic codes) over 1 year. Secondary outcomes included stroke/transient ischemic attack (TIA) and nonvertebral fracture. In the osteoporosis cohort (n = 16,235 pairs), mean age was 71 years, and 93% were female. There was higher risk of AF with ZA compared with denosumab over 1 year (incidence rate [IR] = 18.6 versus 14.9 per 1000 person-years; hazard ratio [HR] = 1.25; 95% confidence interval [CI] 1.04 to 1.50). In the malignancy cohort (n = 7732 pairs), mean age was 70 years, and 66% were female. There was a numerically higher, albeit not statistically significant, risk of AF with ZA compared with denosumab over 1 year (IR = 46.9 versus 39.0 per 1000 person-years; HR = 1.19; 95% CI 1.00 to 1.43; p = 0.06). No difference in stroke/TIA rates occurred. In the malignancy cohort, ZA was less effective than denosumab at preventing nonvertebral fractures (HR = 1.32; 95% CI 1.01 to 1.74). Compared with denosumab, ZA treatment for osteoporosis and possibly for malignancy-related bone disease is associated with modestly increased risk of incident AF in the first year of treatment. © 2020 American Society for Bone and Mineral Research (ASBMR).     

Early bioprosthesis failure in mitral valve replacement

The causes of early bioprosthesis failure include infective endocarditis, pannus formation, and structural valve deterioration. We reported a patient who suffered from early mitral bioprosthesis failure due to leaflets restricted by the subvalvular apparatus and early pannus formation. In patients with symptoms relapse and mitral regurgitation recurrence early after mitral valve replacement, early pannus formation needs to be anticipated, and surgical intervention should be performed if symptoms persist after medical treatment.     

Pig kidney xenotransplantation: Progress toward clinical trials

Pig organ xenotransplantation offers a solution to the shortage of deceased human organs for transplantation. The pathobiological response to a pig xenograft is complex, involving antibody, complement, coagulation, inflammatory, and cellular responses. To overcome these barriers, genetic manipulation of the organ‐source pigs has largely been directed to two major aims—(a) deletion of expression of the known carbohydrate xenoantigens against which humans have natural (preformed) antibodies, and (b) transgenic expression of human protective proteins, for example, complement‐ and coagulation‐regulatory proteins. Conventional (FDA‐approved) immunosuppressive therapy is unsuccessful in preventing an adaptive immune response to pig cells, but blockade of the CD40:CD154 costimulation pathway is successful. Survival of genetically engineered pig kidneys in immunosuppressed nonhuman primates can now be measured in months. Non‐immunological aspects, for example, pig renal function, a hypovolemia syndrome, and rapid growth of the pig kidney after transplantation, are briefly discussed. We suggest that patients on the wait‐list for a deceased human kidney graft who are unlikely to receive one due to long waiting times are those for whom kidney xenotransplantation might first be considered. The potential risk of infection, public attitudes to xenotransplantation, and ethical, regulatory, and financial aspects are briefly addressed.     

Critically ill,tubular injury,delayed early recovery: characteristics of acute kidney disease with renal oxalosis

ObjectsThis study aimed to analyze the clinicopathological features of acute kidney disease (AKD) with renal oxalosis.MethodsData for biopsy-proven AKD with oxalosis diagnosed from Jan 2011 to Oct 2018 was collected. The underlying diseases, dietary habits, clinical and pathological characteristics of newly emerging kidney disease were analyzed. The long-term renal prognosis was observed.ResultsA total of 23 patients were included, comprised of 18 men and 5 women with a mean age of 51.6 ± 15.9 years. The peak Scr was 669.9 ± 299.8 μmol/L, and 95.7% of patients had stage 3 acute kidney injury (AKI). Drug-induced tubulointerstitial nephritis (TIN) was the most common cause (65.2%) of AKD, followed by severe nephrotic syndrome (17.4%). All patients had pathological changes indicating TIN, and 11 patients were complicated with the newly emerging glomerular disease (GD). The risk of oxalosis caused by increased enterogenous oxalate absorption accounted for only 26.1%, and others came from new kidney diseases. The majority (75%) of abundant (medium to severe) oxalosis occurred in patients without GD. There were no significant differences in the score for tubular injury (T-IS) and interstitial inflammation with different severities of oxalosis. Rate of Scr decrease (ΔScr%) at 2 weeks was negatively correlated with the severity of oxalosis (R = −0.542, p = 0.037), score for T-IS (R = −0.553, p = 0.033), and age (R = −0.736, p = 0.002). The decrease in Scr at 4 weeks was correlated with T-IS (R = −0.433), but had no correlation with oxalosis.ConclusionsThe present findings revealed that 95.7% of AKD with secondary renal oxalosis occurred in critically ill patients. AKD from tubular injury was the prominent cause. Severe oxalosis contributed to delayed early recovery of AKD.     

Characteristics affecting cervical sagittal alignment in patients with chronic low back pain

BackgroundSagittal spino-pelvic malalignment in patients with chronic low back pain (CLBP) have been reported in the past, which may also affect cervical spine lesions. The purpose of this study is to investigate the cervical alignment in patients with CLBP.MethodOf the patients who visited an orthopedic specialist due to low back pain lasting more than three months, 121 cases (average 71.5-years-old, 46 male and 75 female) with whole standing spinal screening radiographs were reviewed (CLBP group). Cervical parameters included cervical lordosis (CL), C2–C7 sagittal vertical axis (C2-7 SVA), and the T1 slope minus CL (T1S-CL). Cervical spine deformity was defined as C2-7 SVA >4 cm, CL <0°, or T1S-CL ≧20°. We compared the cervical alignment of these patients with 121 age and gender matched volunteers (control group).ResultsThe prevalence of cervical spine deformity was significantly higher in the CLBP group than in the control group (20.7% vs. 10.7%, P = 0.034). The mean CL was smaller in the CLBP group than in the control group (16.1° vs. 21.4°, P = 0.002). The mean C2-7 SVA was 17.6 mm vs. 18.7 mm in the CLBP group and in the control group, respectively (P = 0.817). The mean T1S-CL was larger in the CLBP group than in the control group (9.1° vs. 3.5°, P < 0.001). Multivariate analysis showed that people with CLBP were more likely to have cervical deformities than people without CLBP (odds ratio 2.16, 95% confidence interval 1.006 to 4.637).ConclusionsThis study results suggest that people with CLBP present with worse cervical sagittal alignment and higher prevalence of cervical spine deformities than age and gender matched volunteers with no CLBP. This means CLBP impacts cervical spine lesions negatively.Level of evidenceⅣ     

Podocyte EGFR Inhibits Autophagy Through Upregulation of Rubicon in Type 2 Diabetic Nephropathy

Renal epidermal growth factor receptor (EGFR) signaling is activated in models of diabetic nephropathy (DN), and inhibition of the EGFR signaling pathway protects against the development of DN. We have now determined that in cultured podocytes, high glucose led to increases in activation of EGFR signaling but decreases in autophagy activity as indicated by decreased beclin-1 and inhibition of LC3B autophagosome formation as well as increased rubicon (an autophagy inhibitor) and SQSTM1 (autophagy substrate). Either genetic (small interfering [si]EGFR) or pharmacologic (AG1478) inhibition of EGFR signaling attenuated the decreased autophagy activity. In addition, rubicon siRNA knockdown prevented high glucose–induced inhibition of autophagy in podocytes. We further examined whether selective EGFR deletion in podocytes affected the progression of DN in type 2 diabetes. Selective podocyte EGFR deletion had no effect on body weight or fasting blood sugars in either db/db mice or nos3^−/−; db/db mice, a model of accelerated type 2 DN. However selective podocyte EGFR deletion led to relative podocyte preservation and marked reduction in albuminuria and glomerulosclerosis, renal proinflammatory cytokine/chemokine expression, and decreased profibrotic and fibrotic components in nos3^−/−; db/db mice. Podocyte EGFR deletion led to decreased podocyte expression of rubicon, in association with increased podocyte autophagy activity. Therefore, activation of EGFR signaling in podocytes contributes to progression of DN at least in part by increasing rubicon expression, leading to subsequent autophagy inhibition and podocyte injury.     

An analysis of the ergonomic risk of surgical trainees and experienced surgeons during laparoscopic procedures

BackgroundWork-related musculoskeletal injuries have been increasingly recognized to affect surgeons. It is unknown whether such injuries also affect surgical trainees. The purpose of this study was to assess the ergonomic risk of surgical trainees as compared with that of experienced surgeons.MethodsErgonomic data were recorded from 9 surgeons and 11 trainees. Biomechanical loads during surgery were assessed using motion tracking sensors and electromyography sensors. Demanding and static positions of the trunk, neck, right/left shoulder, as well as activity from the deltoid and trapezius muscles bilaterally were recorded. In addition, participants reported their perceived discomfort on validated questionnaires.ResultsA total of 87 laparoscopic general surgery cases (48 attendings and 39 trainees) were observed. Both trainees and attendings spent a similarly high percentage of each case in static (>60%) and demanding positions (>5%). Even though residents reported overall more discomfort, all participants shared similar ergonomic risk with the exception of trainees’ trunk being more static (odds ratio: –11.42, P = .006).ConclusionSurgeons are prone to ergonomic risk. Trainees are exposed to similar postural ergonomic risk as surgeons but report more discomfort and, given that musculoskeletal injuries are cumulative over time, the focus should be on interventions to reduce ergonomic risk in the operating room.     

Protective effect of hydroxysafflor yellow A on MSCs against senescence induced by D-galactose

Objective To examine the protective effects of hydroxysafflor yellow A (HSYA) against the senescence of mesenchymal stem cells (MSCs) induced by D-galactose (D-gal) in vitro, and investigate the potential mechanism involved. Methods Grouping experiment, Normal control (NC) group: conventional culture with complete medium; Senescence group: MSCs were cultured for 48 h with complete medium containing 10 g/L D-gal; HSYA group: on the basis of senescence induction, HSYA with the suitable concentration was used to protect MSCs. The key experimental indices associated with oxidative stress, inflammatory response, cell senescence, proliferation and apoptosis were measured through chemical colorimetry, β-galactosidase staining, EdU incorporation and flow cytometry, respectively. The relative quantity (RQ) of proteins related closely to cell proliferation, apoptosis, and NF-κB signaling were measured by Western blotting. Results As compared with Senescence group, treatment with HSYA (120 mg/L) effectively ameliorated the adverse situation of MSCs. Oxidation stress and inflammation along with D-Gal induction was dramatically alleviated in MSCs; The β-Gal-positive staining indicated that MSC senescence was significantly mitigated; The proliferative capability of MSCs was significantly increased by up-regulating PCNA and inhibiting p16 expression; The anti-apoptotic effect on MSCs was exerted by down-regulating the RQ of cleaved Caspase-3 and Bax; The activity of NF-κB signaling in MSCs was notably suppressed through inhibiting phosphorylation of IKKβ and p65. Conclusion HSYA (120 mg/L) significantly delayed the D-Gal-induced senescence process in MSCs through attenuating inflammatory reaction and oxidative stress, and suppressing the activity of NF-κB signaling.