Do 'Surgeon Champions' and High-Volume Surgeons Have Lower Rates of Periprosthetic Femur Fracture? Perspective From a State-Wide Quality Improvement Registry.

BACKGROUND: Recently, a state-wide registry identified fracture as a major cause of total hip arthroplasty revision. There were 52.8% of revisions occurring within 6 months (fracture leading cause). Registry sites have a 'surgeon champion' who acts as liaison and advocate. This study evaluated the effect of surgeon volume and role of 'surgeon champion' on fracture rates. METHODS: There were 95,948 cases from 2012 to 2019 queried with peri-implant femoral fractures identified (within 6 months). Funnel plots were generated to compare individual surgeon-specific fracture rates. Surgeons who had a fracture rate below the confidence interval were labeled 'green' (lower than mean), within were 'yellow' (no difference), and above were 'red' (significantly higher). RESULTS: For all surgeons, 19.6% were red, 72.1% yellow, and 8.3% green. There were 17.2% 'surgeon champions' and 6.2% 'nonchampions' that were green (P = .01), while 20.7 and 19.3% were red (P = .82). There was a significant association between volume and performance (P < .01). No surgeons in the lower two quartiles (<84; 84 to 180 cases), while 4 and 29% of higher-volume surgeons (181 to 404; >404 cases) were green. There was no statistical difference in red status by volume (P = .53). CONCLUSION: 'Surgeon champions' and high-volume surgeons were more likely to be high performers but not less likely to be low performers. Active involvement in quality improvement and/or high volume was associated with better outcomes but did not impart complication immunity. 'Green' surgeons should mentor colleagues to help reduce fractures by re-evaluating modifiable factors. Analyzing outcomes to promote quality and decrease complications is paramount.

Investigation of HDAC8-ligands' intermolecular forces through molecular dynamics simulations: profiling of non-bonding energies to design potential compounds as new anti-cancer agents.

Histone deacetylases are zinc-dependent isoform enzymes and play important role in cellular homeostasis. Among these, HDAC8 is a potential anticancer drug target. To design new inhibitors using protein-ligand energy profiles, an all atom molecular dynamics (MD) simulations were carried out on nine HDAC8-ligand co-crystals (PDBs: 1T64, 1T69, 1T67, 3F07, 1W22, 1VKG, 5FCW, 3SFF and 3SFH). TSN, SHH, B3N, AGE, NHB, CRI, 5YA, 0DI and 1DI are ligands of PDBs, respectively. For these HDAC8-ligands, relative Gibbs binding free energy (ΔGbind) from MM/PBSA method and non-bonding energies (NBE) are in agreement with each other (r2=0.678). Therefore, the NBEs are used to analyze ligands' sub-structures, namely zinc-binding, linker and CAP groups. For linker/CAP regions, this identified carbonyl, amide, and sulfonamide moieties as desirable and alkyl/aryl moieties as electrostatically unfavourable. Using this information, systematically new compounds were designed and subjected to MD simulations. This resulted in seven compounds (NC-I to NC-VII) with encouraging energy profiles (NBE: -76.25 to -127.09 kcal/mol; ΔGbind: -17.21 to -57.42 kcal/mol) in comparison to that of the HDAC8 ligands (NBE: -46.25 to -106.29 kcal/mol; ΔGbind: -14.74 to -49.52 kcal/mol). From these, NC-VI showed best energy profile (NBE = -126.15 kcal/mol; ΔGbind = -57.42 kcal/mol) suggesting its binding affinity and thermodynamic stability. In addition to this, NC-II and NC-III have shown promising NBE and ΔGbind profiles. These may serve as lead molecules for exploration against HDAC8 in cancer therapy. This has provided a basis for designing new compounds with improved NBE and ΔGbind profiles by modifying the unfavourable or not so favourable regions of ligands. [Formula: see text] Communicated by Ramaswamy H. Sarma.

Improvement in Depression and Physical Health Following Total Joint Arthroplasty.

BACKGROUND: Depression is a common co-morbid condition seen in arthroplasty patients. Pain and depression have been understood to influence one another, which may explain why this patient group experiences higher rates of depression than the general population. Arthroplasty can relieve pain and improve function, which may thereby initiate an improvement in the patient's depressive symptoms. METHODS: This retrospective study examined physical and mental domain outcomes of Short Form-36 health-related quality of life questionnaire among 146 patients who underwent primary hip or knee arthroplasty for osteoarthritis at a single institution during 2001-2004. These patients were classified into "depressed/anxious" and "non-depressed" groups based on their pre-operative mental component summary (MCS), with MCS < 42 defining depression. MCS and the subscales from the 36-Item Short-Form Health Survey form expected to be influenced by arthroplasty, Physical Function, Pain, and Role Physical were examined at 3 months and 1 year post-operative. RESULTS: At 1 year, 66.7% of the "depressed/anxious" group reported MCS > 42, suggesting improvement of their depressive symptoms. Both groups reported similar improvements in their 36-Item Short-Form Health Survey subscale scores for Pain and Physical Function. However, the depressed group's scores were lower than the non-depressed group's at all time points. CONCLUSION: Arthroplasty significantly improved Physical Function and Pain in depressed patients, while their depressive symptoms improved. This improvement may be in response to the resolution of physical symptoms and represents an additional benefit to this elective surgery. Further studies, in larger populations, are needed to establish patient characteristics associated with non-resolution of depressive symptoms and the role of mental health interventions to optimize outcomes for hip and knee arthroplasty patients.

Bioactivity of novel transition metal complexes of N'-[(4-methoxy)thiobenzoyl]benzoic acid hydrazide.

Cu(II), Fe(III), and Mn(II) complexes of a novel ligand N'-[(4-methoxy)thiobenzoyl]benzoic acid hydrazide (H(2)mtbh) have been synthesized and characterized by elemental analyses, IR, UV-vis, NMR, mass, EPR and Mössbauer spectroscopy. The results suggest a square planar structure for [Cu(Hmtbh)Cl] and [Cu(mtbh)] whereas an octahedral structure for [Mn(Hmtbh)(2)] and [Fe(Hmtbh)(mtbh)]. Mn(II) and Fe(III) complexes were found to inhibit proliferation of HT29 cells. [Mn(Hmtbh)(2)] and [Fe(Hmtbh)(mtbh)] inhibited proliferation of HT29 cells with half maximal inhibition (IC(50)) of 8.15+/-0.87 and 68.1+/-4.8 microM, respectively, whereas H(2)mtbh showed growth inhibition with IC(50) of 90.9+/-7.8 microM and were able to inhibit NMT activity in vitro. Mn(II) and Fe(III) complexes inhibited NMT activity in a dose dependent manner with IC(50) values of 20+/-2.2 and 60+/-7.2 microM, respectively, whereas ligand (H(2)mtbh) displayed IC(50) of 3.2+/-0.5 mM.

Protective effect of resveratrol against pentylenetetrazole-induced seizures and its modulation by an adenosinergic system.

The effect of trans-resveratrol (resveratrol), a polyphenolic compound with potent antioxidant activity, was investigated against pentylenetetrazole (PTZ) induced seizures in rats. Resveratrol (20, 40, and 80 mg/kg i.p.) administered 20 min prior to convulsive challenge with PTZ (60 mg/kg i.p.) dose dependently reduced the percent incidence of generalized tonic-clonic convulsions. Resveratrol (40 mg/kg) also potentiated the effect of sodium valproate (150 mg/kg) and diazepam (2 mg/kg) against PTZ-induced seizures. Since adenosine, an endogenous anticonvulsant, has been demonstrated to modulate the action of various antiepileptics, experiments were also carried out to determine whether an adenosinergic mechanism is involved in the anticonvulsant action of resveratrol. When a subanticonvulsant dose of adenosine (500 mg/kg) was administered together with resveratrol, a significant reduction in the percent incidence of generalized tonic-clonic convulsions was observed. Moreover, the nonspecific adenosine receptor antagonist theophylline (50 mg/kg i.p.) significantly reversed the resveratrol-induced protection, whereas the specific adenosine A2 receptor antagonist 3,7-dimethyl-1-propargylxanthine (1 mg/kg i.p.) could not reverse the resveratrol-induced protection. The findings of the present study suggest an antiepileptic potential of resveratrol and that an adenosinergic mechanism may play a role in its anticonvulsant activity.