Increased complications in geriatric patients with a fracture of the hip whose postoperative weight-bearing is restricted: an analysis of 4918 patients.

AIMS: The aims of this study were to evaluate the incidence of postoperatively restricted weight-bearing and its association with outcome in patients who undergo surgery for a fracture of the hip. PATIENTS AND METHODS: Patient aged > 60 years undergoing surgery for a hip fracture were identified in the 2016 National Surgical Quality Improvement Program (NSQIP) Hip Fracture Targeted Procedure Dataset. Analysis of the effect of restricted weight-bearing on adverse events, delirium, infection, transfusion, length of stay, return to the operating theatre, readmission and mortality within 30 days postoperatively were assessed. Multivariate regression analysis was used to adjust for confounding demographic, comorbid and procedural characteristics. RESULTS: Of the 4918 patients who met inclusion criteria, 3668 (63.53%) were allowed to weight-bear as tolerated postoperatively. Controlling for patient and procedural factors, multivariate odds of any adverse event, major adverse event, delirium, infection, transfusion, length of stay ≥ 75th percentile (six days) and mortality within 30 days were all higher in patients with weight-bearing restrictions. Notably, there were no differences for thromboembolic events, return to the operating theatre or readmission within 30 days between the groups. CONCLUSION: Elderly patients with a fracture of the hip with postoperative weight-bearing restrictions have a significantly greater risk of developing most adverse events compared with those who are encouraged to weight-bear as tolerated. These findings emphasize the importance of immediate weight-bearing as tolerated to optimize the outcome in these frail patients; however nearly 25% of surgeons fail to meet this evidence-based guideline. Cite this article: Bone Joint J 2018;100-B:1377-84.

Aseptic revision total hip arthroplasty in the elderly : quantifying the risks for patients over 80 years old.

AIMS: The aim of this study was to compare the rate of perioperative complications following aseptic revision total hip arthroplasty (THA) in patients aged ≥ 80 years with that in those aged < 80 years, and to identify risk factors for the incidence of serious adverse events in those aged ≥ 80 years using a large validated national database. PATIENTS AND METHODS: Patients who underwent aseptic revision THA were identified in the 2005 to 2015 National Surgical Quality Improvement Program (NSQIP) database and stratified into two age groups: those aged < 80 years and those aged ≥ 80 years. Preoperative and procedural characteristics were compared. Multivariate regression analysis was used to compare the risk of postoperative complications and readmission. Risk factors for the development of a serious adverse event in those aged ≥ 80 years were characterized. RESULTS: The study included 7569 patients aged < 80 years and 1419 were aged ≥ 80 years. Multivariate analysis showed a higher risk of perioperative mortality, pneumonia, urinary tract infection and the requirement for a blood transfusion and an extended length of stay in those aged ≥ 80 years compared with those aged < 80 years. Independent risk factors for the development of a serious adverse event in those aged ≥ 80 years include an American Society of Anesthesiologists score of ≥ 3 and procedures performed under general anaesthesia. CONCLUSION: Even after controlling for patient and procedural characteristics, aseptic revision THA is associated with greater risks in patients aged ≥ 80 years compared with younger patients. This is important for counselling and highlights the need for medical optimization in these vulnerable patients. Cite this article: Bone Joint J 2018;100-B:143-51.

The uncertainty of predicting intact anterior cruciate ligament degeneration in terms of structural properties using T(2)(*) relaxometry in a human cadaveric model.

The combination of healing anterior cruciate ligament (ACL) volume and the distributions of T2(*) relaxation times within it have been shown to predict the biomechanical failure properties in a porcine model. This MR-based prediction model has not yet been used to assess ligament degeneration in the aging human knee. Using a set of 15 human cadaveric knees of varying ages, we obtained in situ MR measures of volume and T2(*) of the intact ACL and then related these MR variables to biomechanical outcomes (maximum and yield loads, linear stiffness) obtained via ex vivo failure testing. Using volume in conjunction with the median T2(*) value, the multiple linear regression model did not predict maximum failure load for the intact human ACL; R(2)=0.23, p=0.200. Similar insignificant results were found for yield load and linear stiffness. Naturally restricted distributions of the intact ligament volume and T2(*) (demonstrated by the respective Z-scores) in an older cadaveric population were the likely reason for the insignificant results. These restricted distributions may negatively affect the ability to detect a correlation when one exists. Further research is necessary to understand the relationship of MRI variables and ligament degeneration. While this study failed to find a significant prediction of human biomechanical outcome using these MR variables, with further research, an MR-based approach may offer a tool to longitudinally assess changes in cruciate ligament degradation.

Does mammalian heart contain only the M2 muscarinic receptor subtype?

Five muscarinic acetylcholine receptor (mAChR) subtypes, m1-m5, have been cloned and sequenced to date. The question as to which mAChR subtypes exist in mammalian heart has been studied extensively and is still under considerable debate. We used the reverse transcriptase-polymerase chain reaction to amplify mRNA from adult rat ventricular myocytes, and found that these cells express mRNA for m1 and m2 mAChRs. Immunocytochemical analysis confirmed that m1 and m2, but not m3, mAChR proteins are present on the surface of these cells. Finally, the functional significance of these receptors was examined. Administration of the m1 mAChR antagonist pirenzepine inhibited the stimulatory effect of the muscarinic agonist carbachol on Ca transients. These findings are consistent with the presence of at least two mAChR subtypes in mammalian heart, m1 and m2, and suggest that activation of m1 mAChRs is involved in the stimulatory effects of muscarinic agonists in mammalian heart.

Protective role of bradykinin in cardiac anaphylaxis. Coronary-vasodilating and antiarrhythmic activities mediated by autocrine/paracrine mechanisms.

Cardiac anaphylaxis, an acute ischemic dysfunction comprising coronary vasoconstriction and arrhythmias, is a model of clinically recognized immediate hypersensitivity reactions affecting the heart. Bradykinin, a mediator of hypersensitivity, is also a potent coronary vasodilator, acting via nitric oxide and prostacyclin production. Because ischemia increases bradykinin outflow from the heart, we questioned whether bradykinin might mitigate anaphylactic coronary vasoconstriction. Antigen challenge of hearts isolated from presensitized guinea pigs was associated with an approximately 30% increase in bradykinin overflow. Furthermore, (1) when the half-life of bradykinin was prolonged with the kininase II/angiotensin-converting enzyme inhibitors captopril and enalaprilat, anaphylactic coronary vasoconstriction was attenuated and reversed, and arrhythmias were alleviated; (2) the bradykinin B2-receptor antagonist HOE 140 prevented these effects; and (3) HOE 140 exacerbated both anaphylactic coronary vasoconstriction and arrhythmias. During cardiac anaphylaxis, the coronary overflow of cGMP, a marker of nitric oxide production, and 6-ketoprostaglandin F1 alpha, a stable prostacyclin metabolite, increased two-fold and fourfold, respectively. Because neither enalaprilat nor HOE 140 affected these changes, the enhanced overflow of cGMP and 6-ketoprostaglandin F1 alpha is likely to reflect the actions of other hypersensitivity mediators (eg, histamine and leukotrienes). We postulate that bradykinin plays a protective role in cardiac anaphylaxis by accumulating at the luminal surface of the coronary endothelium and promoting, in an autocrine mode, a B2-receptor-mediated production of nitric oxide and prostacyclin in concentrations sufficient to elicit a paracrine effect on coronary vascular smooth muscle, thus opposing the vasoconstricting effects of other anaphylactic mediators.

Nitric oxide is a mediator of hypoxic coronary vasodilatation. Relation to adenosine and cyclooxygenase-derived metabolites.

Hypoxia is a potent coronary-vasodilating signal; its mechanisms are still controversial. We have assessed the possible role of nitric oxide (NO) in hypoxic coronary vasodilatation (HCVD) in isolated guinea pig hearts perfused at constant pressure. HCVD was elicited by a 1-minute 100% N2 exposure; coronary flow doubled within 1 minute of hypoxia (early phase) and returned to baseline within 40 seconds after reoxygenation (late phase). The early phase of HCVD was associated with a rapid approximately eightfold increase in cGMP overflow, an indication of NO release. The specific NO synthase inhibitor N omega-methyl-L-arginine (NMA, 0.1-1 mM) antagonized HCVD and the associated increase in cGMP spillover (maximum inhibition, approximately 65%); excess arginine (1.2 mM) prevented both effects. The late phase of HCVD was associated with an increase in adenosine overflow and was attenuated by the adenosine receptor antagonist BW A1433 (1 microM; maximum inhibition, approximately 45%). Indomethacin (10 microM) inhibited HCVD in spontaneously beating hearts by approximately 35% but had no effect in hearts paced at faster rates. NMA and BW A1433 were more effective in combination than alone (maximum inhibition, approximately 72%). However, irrespective of the concentrations used, there was no synergism among the anti-HCVD effects of NMA, BW A1433, and indomethacin, nor was HCVD completely inhibited by the antagonists, whether alone or in combination. Our findings indicate that NO is an important mediator of the early phase of HCVD, whereas additional mechanisms and/or factors, including adenosine and vasodilatatory prostaglandins, contribute to the late phase.

L-arginine, but not N alpha-benzoyl-L-arginine ethyl ester, is a precursor of endothelium-derived relaxing factor.

N alpha-benzoyl-L-arginine ethyl ester (BAEE) is a vasorelaxant which resembles an arginine-containing peptide; its action may be partially endothelium-dependent. Because L-arginine (ARG) has little potency as a vasorelaxant, it has been proposed that an arginine-containing peptide, rather than free ARG, is the immediate precursor of endothelium-derived relaxing factor/nitric oxide (EDRF/NO). In the present study we have characterized pharmacologically the vasorelaxant effect of BAEE and assessed the ability of BAEE to serve as a substrate for EDRF/NO synthesis. BAEE elicited a concentration-dependent vasorelaxation of guinea pig pulmonary artery (EC50 of 0.36 +/- 0.05 mM). This vasorelaxation was neither antagonized by -NG-methyl-L-arginine (100 microM), a competitive inhibitor of EDRF/NO synthesis from ARG, nor potentiated by superoxide dismutase (60 U/ml), a superoxide anion scavenger that prolongs EDRF lifetime. Additionally, compound LY 83583 (1 microM) and methylene blue (10 microM), inhibitors of soluble guanylyl cyclase, failed to block BAEE-induced vasorelaxation. Moreover, endothelium removal potentiated the vasorelaxant effect of BAEE 3-fold. Thus, BAEE-induced vasorelaxation is mediated by a direct action on vascular smooth muscle that is unrelated to EDRF/NO synthesis. Furthermore, ARG, but not BAEE, overcame the inhibition by NG-methyl-L-arginine of the acetylcholine-induced endothelium-dependent cyclic GMP accumulation in guinea pig aortic rings and of A23187-induced nitrite formation by cultured bovine aortic endothelial cells (nitrite is a convenient indicator of NO biosynthesis). Thus, BAEE cannot substitute for ARG as a substrate for EDRF/NO biosynthesis. Collectively, our findings support the notion that free ARG, rather than an arginine-containing peptide related to BAEE, is the immediate biosynthetic precursor of EDRF/NO.