Evidence-based strategies to reduce the incidence of postoperative delirium: a narrative review

Delirium is one of the most commonly occurring postoperative complications in older adults. It occurs due to the vulnerability of cerebral functioning to pathophysiological stressors. Identification of those at increased risk of developing delirium early in the surgical pathway provides an opportunity for modification of predisposing and precipitating risk factors and effective shared decision-making. No single delirium prediction tool is used widely in surgical settings. Multi-component interventions to prevent delirium involve structured risk factor modification supported by geriatrician input; these are clinically efficacious and cost effective. Barriers to the widespread implementation of such complex interventions exist, resulting in an ‘implementation gap’. There is a lack of evidence for pharmacological prophylaxis for the prevention of delirium. Current evidence suggests that avoidance of peri-operative benzodiazepines, careful titration of anaesthetic depth guided by processed electroencephalogram monitoring and treatment of pain are the most effective strategies to minimise the risk of delirium. Addressing postoperative delirium requires a collaborative, whole pathway approach, beginning with the early identification of those patients who are at risk. The research agenda should continue to examine the potential for pharmacological prophylaxis to prevent delirium while also addressing how successful models of delirium prevention can be translated from one setting to another, underpinned by implementation science methodology.     

Multiscale quantification of morphological heterogeneity with creation of a predictor of longer survival in glioblastoma

Intratumor heterogeneity is a main cause of the dismal prognosis of glioblastoma (GBM). Yet, there remains a lack of a uniform assessment of the degree of heterogeneity. With a multiscale approach, we addressed the hypothesis that intratumor heterogeneity exists on different levels comprising traditional regional analyses, but also innovative methods including computer-assisted analysis of tumor morphology combined with epigenomic data. With this aim, 157 biopsies of 37 patients with therapy-naive IDH-wildtype GBM were analyzed regarding the intratumor variance of protein expression of glial marker GFAP, microglia marker Iba1 and proliferation marker Mib1. Hematoxylin and eosin stained slides were evaluated for tumor vascularization. For the estimation of pixel intensity and nuclear profiling, automated analysis was used. Additionally, DNA methylation profiling was conducted separately for the single biopsies. Scoring systems were established to integrate several parameters into one score for the four examined modalities of heterogeneity (regional, cellular, pixel-level and epigenomic). As a result, we could show that heterogeneity was detected in all four modalities. Furthermore, for the regional, cellular and epigenomic level, we confirmed the results of earlier studies stating that a higher degree of heterogeneity is associated with poorer overall survival. To integrate all modalities into one score, we designed a predictor of longer survival, which showed a highly significant separation regarding the OS. In conclusion, multiscale intratumor heterogeneity exists in glioblastoma and its degree has an impact on overall survival. In future studies, the implementation of a broadly feasible heterogeneity index should be considered.     

Biomechanical comparison of stemless humeral components in total shoulder arthroplasty

BackgroundThe purpose of this study was to compare initial fixation strength between various stemless and stemmed humeral components and to correlate implant fixation strength with bone mineral density (BMD).MethodsFive humeral stem designs were investigated: Stemless-A (four hollow fins), Stemless-B (central body, three solid fins), Stemless-C (central screw, peripheral rim-fit), Short stem (50 mm), and Standard stem (130 mm). Fifty cadaveric human humerii were obtained and divided into five groups. BMD within the humeral head was determined for all samples. The mean BMD was similar between groups. The 25 samples with the lowest and highest BMDs were categorized as “Low” and “High,” respectively, with a BMD threshold of 0.35 g/cm², creating BMD subgroups. After implantation, each sample underwent a standardized biomechanical testing protocol, with axial loading followed by torsional loading. Sensors attached to the specimen recorded micromotion throughout testing. Axial loading consisted of cyclic loading for 100 cycles at 3 peak forces (220, 520, and 820 N). Torsional loading consisted of 100 cycles of internal/external rotation at 0.1 Hz at 6 peak torques, or until failure (±2.5, 5, 7.5, 10, 12.5, and 15 Nm). Failure was defined as the torque at which any bone fracture, implant detachment from anchor/stem, or an excess of 50° internal/external rotation occurred. Groups and BMD subgroups were compared.ResultsAt maximal axial loading, Stemless-B demonstrated greater micromotion (540 μm) than Stemless-C (192 μm) (P = .003). Stemless-B and Stemless-A (387 μm) also had greater micromotion than Short stem (118 μm, P < .001, P = .03) and Standard stem (85 μm, P < .001, P = .01). When comparing low-BMD samples at maximal axial loading, these differences were accentuated, but comparison of high-BMD samples showed no significant differences between groups. Torsional testing demonstrated that Standard stem failed at greater torque (7.2 Nm) than Stemless-B (2.3 Nm, P < .001), Stemless-A (1.9 Nm, P < .001), and Stemless-C (3.9 Nm, P = .01). When comparing torsional testing results of low-BMD samples, both Standard stem and Short stem failed at greater torque than Stemless-B (P = .02, P = .003) and Stemless-A (P = .03, P = .004) but failed at a similar torque to Stemless-C. Torsional testing of high-BMD samples showed that Standard stem failed at a greater torque than all stemless designs.ConclusionStemless humeral implants should be used with caution in low-BMD settings (<0.35 g/cm²). A central screw and peripheral rim-fit stemless anchor design demonstrated greater fixation strength at low BMD when compared with other designs, while all stemless designs performed similarly at high BMD.Level of evidenceBasic Science Study; Cadaveric Study     

Effect of iron deficiency without anaemia on days alive and out of hospital in patients undergoing valvular heart surgery

Comprehensive evidence regarding the treatment of non-anaemic iron deficiency in patients undergoing valvular heart surgery is lacking. This study aimed to investigate the association between non-anaemic iron deficiency and postoperative outcomes in these patients. We retrospectively analysed 321 patients of which 180 (56%) had iron deficiency (defined as serum ferritin < 100 ng.ml^-1 or < 300 ng.ml^-1 with transferrin saturation < 20%). While the iron-deficient group had lower pre-operative haemoglobin levels than the non-iron deficient group (median (IQR [range]) 134 (127–141 [120–172]) g.l^-1, 143 (133–150 [120–179]) g.l^-1, p = 0.001), there was no between-group difference in allogeneic red blood cell transfusion. Median (IQR [range]) days alive and out of hospital at postoperative day 90 was 1 day shorter in the iron-deficient group (80 (77–82 [9–85]) days vs. 81 (79–83 [0–85]) days, p = 0.026). In multivariable analysis, only cardiopulmonary bypass duration (p = 0.032) and intra-operative allogeneic red blood cell transfusion (p = 0.011) were significantly associated with reduced days alive and out of hospital at postoperative day 90. Iron deficiency did not exert any adverse influence on secondary outcomes except length of hospital stay. Our findings indicate that non-anaemic iron deficiency alone is not associated with adverse effects in patients undergoing valvular heart surgery when it does not translate into an increased risk of allogeneic transfusion.     

Comprehensively evaluating cancer survival in children with birth defects: a population-based assessment

Cancer Causes & Control - Congenital malformations are strong risk factors for childhood cancer. Our objective was to determine whether cancer survival differs by birth defect status among...