Association of preoperative beta-blocker use and cardiac complications after major noncardiac surgery: a prospective cohort study.

INTRODUCTION: Cardiac complications after major noncardiac surgery are common and associated with high morbidity and mortality. How preoperative use of beta-blockers may impact perioperative cardiac complications remains unclear. METHODS: In a multicentre prospective cohort study, preoperative beta-blocker use was ascertained in consecutive patients at elevated cardiovascular risk undergoing major noncardiac surgery. Cardiac complications were prospectively monitored and centrally adjudicated by two independent experts. The primary endpoint was perioperative myocardial infarction or injury attributable to a cardiac cause (cardiac PMI) within the first three postoperative days. The secondary endpoints were major adverse cardiac events (MACE), defined as a composite of myocardial infarction, acute heart failure, life-threatening arrhythmia, and cardiovascular death and all-cause death after 365 days. We used inverse probability of treatment weighting to account for differences between patients receiving beta-blockers and those who did not. RESULTS: A total of 3839/10 272 (37.4%) patients (mean age 74 yr; 44.8% female) received beta-blockers before surgery. Patients on beta-blockers were older, and more likely to be male with established cardiorespiratory and chronic kidney disease. Cardiac PMI occurred in 1077 patients, with a weighted odds ratio of 1.03 (95% confidence interval [CI] 0.94-1.12, P=0.55) for patients on beta-blockers. Within 365 days of surgery, 971/10 272 (9.5%) MACE had occurred, with a weighted hazard ratio of 0.99 (95% CI 0.83-1.18, P=0.90) for patients on beta-blockers. CONCLUSION: Preoperative use of beta-blockers was not associated with decreased cardiac complications including cardiac perioperative myocardial infarction or injury and major adverse cardiac event. Additionally, preoperative use of beta-blockers was not associated with increased all-cause death within 30 and 365 days. CLINICAL TRIAL REGISTRATION: NCT02573532.

Regeneration of nerve crush injury using adipose-derived stem cells: A multimodal comparison.

INTRODUCTION: To restore full function following nerve crush injuries is critical but challenging. In an attempt to develop a viable therapy, we evaluated the effect of rat adipose-derived stem cells (rASC) in 2 different settings of a sciatic crush injury model. METHODS: In the first group, after 14 days of nerve crush injury, rASCs were injected distal to the lesion under ultrasound guidance. In the other group, alleviation of compression through clip removal (CR) was combined with epineural injection of rASCs. Gait analyses, MRI, gastrocnemius muscle weight ratio (MWR), and histomorphometry were performed for outcome analysis. RESULTS: CR combined with rASC injection resulted in less muscle atrophy, as evidenced by MWR. These findings are further supported by better functional and anatomical outcomes. DISCUSSION: Animals treated with CR and epineural stem cell injection showed enhanced anatomical and functional recovery. Muscle Nerve 58: 566-572, 2018.

Platelet concentrates in spine fusion: meta-analysis of union rates and complications in controlled trials.

PURPOSE: Platelet concentrates in spine fusion gained increasing popularity among spine surgeons. They avoid morbidity of bone harvest and promise good union rates without additional device-related adverse events. Therefore, they seem to be a safe and effective alternative to common bone substitutes. This meta-analysis assesses the available evidence for union rate and overall complications with the use of platelet concentrates in spine fusion. METHODS: We conducted an online search for relevant controlled trials and extracted data on union rates, complications, and revision rates. These data were synthesized in a meta-analysis using fixed-effects odds ratios (OR). To assess covariates, meta-regression was performed as well. RESULTS: Our search produced 166 results, ten of which were eligible for inclusion. These studies report on a total of 763 patients (328 experimental, 435 controls) with a mean age of 50.3 ± 7.5 years. Mean follow-up was 1.9 ± 0.0.4 years. With the use of platelet concentrates, union rate decreased significantly, OR 0.53 (95 % CI 0.35-0.79, p = 0.002), compared with the control group. There was no statistically significant difference in complication rates OR 1.34 (95 % CI 0.62-2.90, p = 0.46) or in revision rates OR 3.0 (95 % CI 0.90-10.00, p = 0.74). Meta-regression showed no statistically significant influence of randomization, Jadad score, or assessment of fusion. CONCLUSION: The use of platelet concentrates in spine fusion shows significantly decreased union rates compared with the control group. However, complication and revision rates were not significantly increased. The current data do not recommend the use of platelet concentrate in spine fusion.

Complications and cancer rates in spine fusion with recombinant human bone morphogenetic protein-2 (rhBMP-2).

PURPOSE: To quantitatively synthesize the available best evidence for general complications, heterotopic ossification (HO), retrograde ejaculation, cervical swelling, and cancer rates with the use of rhBMP-2 in lumbar and cervical spine fusion. METHODS: We conducted an online search for relevant controlled trials and extracted data on the abovementioned endpoints. Studies were eligible for inclusion if they reported on spinal fusion with rhBMP-2 in humans. Publication bias and heterogeneity were assessed mathematically. These data were synthesized in a meta-analysis using DerSimonian-Laird random effects modeling to calculate pooled odds ratios. RESULTS: We identified 26 studies reporting on a total of 184,324 patients (28,815 experimental, 155,509 controls) with a mean age of 51.1 ± 1.8 years. There was a significantly higher risk of general complications with rhBMP-2 compared to iliac crest bone graft (ICBG) with an odds ratio (OR) of 1.78 (95 %CI 1.20-2.63), (p = 0.004). The odds ratio for HO was 5.57 (95 %CI 1.90-16.36), (p = 0.002), for retrograde ejaculation 3.31 (95 %CI 1.20-9.09), (p = 0.020), and for cervical swelling 4.72 (95 %CI 1.42-15.67), (p = 0.011), all significantly higher in the rhBMP-2 group. The pooled odds ratio for new onset of tumor was 1.35 (95 %CI 0.93-1.96), which represents no statistically significant difference between the groups (p = 0.111). CONCLUSION: rhBMP-2 is associated with a higher rate of general complications as well as retrograde ejaculation, HO, and cervical tissue swelling in spine fusion. There is a slightly increased risk of new onset of tumors, however, without statistical significance.

Anti-inflammatory/tissue repair macrophages enhance the cartilage-forming capacity of human bone marrow-derived mesenchymal stromal cells.

Macrophages are key players in healing processes. However, little is known on their capacity to modulate the differentiation potential of mesenchymal stem/stromal cells (MSC). Here we investigated whether macrophages (Mf) with, respectively, pro-inflammatory and tissue-remodeling traits differentially modulate chondrogenesis of bone marrow derived-MSC (BM-MSC). We demonstrated that coculture in collagen scaffolds of BM-MSC with Mf derived from monocytes polarized with M-CSF (M-Mf), but not with GM-CSF (GM-Mf) resulted in significantly higher glycosaminoglycan (GAG) content than what would be expected from an equal number of BM-MSC alone (defined as chondro-induction). Moreover, type II collagen was expressed at significantly higher levels in BM-MSC/M-Mf as compared to BM-MSC/GM-Mf constructs, while type X collagen expression was unaffected. In order to understand the possible cellular mechanism accounting for chondro-induction, developing monoculture and coculture tissues were digested and the properties of the isolated BM-MSC analysed. We observed that as compared to monocultures, in coculture with M-Mf, BM-MSC decreased less markedly in number and exhibited higher clonogenic and chondrogenic capacity. Despite their chondro-inductive effect in vitro, M-Mf did not modulate the cartilage tissue maturation in subcutaneous pockets of nude mice, as evidenced by similar accumulation of type X collagen and calcified tissue. Our results demonstrate that coculture of BM-MSC with M-Mf results in synergistic cartilage tissue formation in vitro. Such effect seems to result from the survival of BM-MSC with high chondrogenic capacity. Studies in an orthotopic in vivo model are necessary to assess the clinical relevance of our findings in the context of cartilage repair.

FGF2 induces RANKL gene expression as well as IL1ß regulated MHC class II in human bone marrow-derived mesenchymal progenitor stromal cells.

OBJECTIVE: Human bone marrow mesenchymal stromal cells (hBM-MSC) are being applied in tissue regeneration and treatment of autoimmune diseases (AD). Their cellular and immunophenotype depend on isolation and culture conditions which may influence their therapeutic application and reflect their in vivo biological functions. We have further characterised the phenotype induced by fibroblast growth factor 2 (FGF2) on healthy donor hBM-MSC focusing on the osteoimmunological markers osteoprotegerin (OPG), receptor activator of nuclear factor kB (RANK), RANK ligand (RANKL) and HLA-DR and their regulation of expression by the inflammatory cytokines IL1ß and IFNγ. METHODS: RANK, RANKL, OPG and HLA-DR expression in hBM-MSC expanded under specific culture conditions, were measured by RT-PCR and flow cytometry. MAPKs induction by FGF2, IL1ß and IFNγ in hBM-MSC was analysed by immunoblotting and RT-PCR. RESULTS: In hBM-MSC, OPG expression is constitutive and FGF2 independent. RANKL expression depends on FGF2 and ERK1/2 activation. IL1ß and IFNγ activate ERK1/2 but fail to induce RANKL. Only IL1ß induces P38MAPK. The previously described HLA-DR induced by FGF2 through ERK1/2 on hBM-MSC, is suppressed by IL1ß through inhibition of CIITA transcription. HLA-DR induced by IFNγ is not affected by IL1ß in hBM-MSC, but is suppressed in articular chondrocytes and lung fibroblasts. CONCLUSIONS: RANKL expression and IL1ß regulated MHC-class II, both induced via activation of the ERK1/2 signalling pathway, are specific for progenitor hBM-MSC expanded in the presence of FGF2. HLA-DR regulated by IL1ß and ERK1/2 is observed on hBM-MSC during early expansion without FGF2 suggesting previous in vivo acquisition. Stromal progenitor cells with this phenotype could have an osteoimmunological role during bone regeneration.

Correlation of (99m) Tc-DPD SPECT/CT Scan Findings and Diagnostic Blockades of Lumbar Medial Branches in Patients with Unspecific Low Back Pain in a Randomized-Controlled Trial.

OBJECTIVE: Zygapophyseal joints are the origin of pain in up to 30% of those with unspecific chronic low back pain. Until recently, no reliable clinical tests have been found to identify the patients who would benefit from denervation of the zygapophyseal joints by medial branch blockades. DESIGN: We performed a prospective randomized placebo-controlled trial to evaluate the value of high-resolution single-photon emission computed tomography (SPECT)/computed tomography (CT) of the lumbar spine prior to any diagnostic infiltration of the medial branches. METHODS: Patients with suspected zygapophyseal joint-related pain were included in the study. After obtaining a SPECT/CT scan of the lumbar spine a set of infiltrations of the medial branches was done with local anesthetics and placebo on different days. Patients and anesthetists were blinded to the results of SPECT/CT and to the infiltrated agents. RESULTS: In a total of 29 study patients, 7 had positive and 22 negative infiltration tests, and 9 had positive and 20 negative SPECT/CT findings. Sensitivity of SPECT/CT for a positive response after diagnostic infiltration was 0.57 (95% confidence interval [CI] 0.18-0.90); specificity was 0.77 (CI 95% 0.55-0.92); odds ratio was 4.53 (CI 95% 0.75-27.40); and diagnostic accuracy was 0.72. CONCLUSION: Compared with diagnostic infiltrations SPECT/CT scans showed only a moderate sensitivity and specificity and, therefore, may not be recommended as a first line diagnostic tool prior to diagnostic infiltrations.

Fibroblast growth factor-2 maintains a niche-dependent population of self-renewing highly potent non-adherent mesenchymal progenitors through FGFR2c.

Bone marrow (BM) mesenchymal stem/stromal cells (MSC) are a heterogeneous population of multipotent progenitors currently under investigation for a variety of applications in regenerative medicine. While self-renewal of stem cells in different tissues has been demonstrated to be regulated by specialized microenvironments called niches, it is still unclear whether a self-renewing niche also exists for MSC. Here, we show that primary human BM cultures contain a population of intrinsically non-adherent mesenchymal progenitors (NAMP) with features of more primitive progenitors than the initially adhering colony-forming units-fibroblast (CFU-f). In fact, NAMP could generate an adherent progeny: (a) enriched with early mesenchymal populations (CD146+, SSEA-1+, and SSEA-4+); (b) with significantly greater proliferation and multilineage differentiation potential in vitro; and (c) capable of threefold greater bone formation in vivo than the corresponding CFU-f. Upon serial replating, NAMP were able to regenerate and expand in suspension as non-adherent clonogenic progenitors, while also giving rise to an adherent progeny. This took place at the cost of a gradual loss of proliferative potential, shown by a reduction in colony size, which could be completely prevented when NAMP were expanded on the initially adhering BM fraction. Mechanistically, we found that NAMP crucially depend on fibroblast growth factor (FGF)-2 signaling through FGFR2c for their survival and expansion. Furthermore, NAMP maintenance depends at least in part on humoral signals distinct from FGF-2. In conclusion, our data show a niche/progenitor organization in vitro, in which the BM adherent fraction provides a self-renewing microenvironment for primitive NAMP.

Recapitulation of endochondral bone formation using human adult mesenchymal stem cells as a paradigm for developmental engineering.

Mesenchymal stem/stromal cells (MSC) are typically used to generate bone tissue by a process resembling intramembranous ossification, i.e., by direct osteoblastic differentiation. However, most bones develop by endochondral ossification, i.e., via remodeling of hypertrophic cartilaginous templates. To date, endochondral bone formation has not been reproduced using human, clinically compliant cell sources. Here, we aimed at engineering tissues from bone marrow-derived, adult human MSC with an intrinsic capacity to undergo endochondral ossification. By analogy to embryonic limb development, we hypothesized that successful execution of the endochondral program depends on the initial formation of hypertrophic cartilaginous templates. Human MSC, subcutaneously implanted into nude mice at various stages of chondrogenic differentiation, formed bone trabeculae only when they had developed in vitro hypertrophic tissue structures. Advanced maturation in vitro resulted in accelerated formation of larger bony tissues. The underlying morphogenetic process was structurally and molecularly similar to the temporal and spatial progression of limb bone development in embryos. In particular, Indian hedgehog signaling was activated at early stages and required for the in vitro formation of hypertrophic cartilage. Subsequent development of a bony collar in vivo was followed by vascularization, osteoclastic resorption of the cartilage template, and appearance of hematopoietic foci. This study reveals the capacity of human MSC to generate bone tissue via an endochondral program and provides a valid model to study mechanisms governing bone development. Most importantly, this process could generate advanced grafts for bone regeneration by invoking a "developmental engineering" paradigm.

Prediction of perioperative myocardial infarction/injury in high-risk patients after noncardiac surgery.

AIMS: Perioperative myocardial infarction/injury (PMI) is a surprisingly common yet difficult-to-predict cardiac complication in patients undergoing noncardiac surgery. We aimed to assess the incremental value of preoperative cardiac troponin (cTn) concentration in the prediction of PMI. METHODS AND RESULTS: Among prospectively recruited patients at high cardiovascular risk (age ≥65 years or ≥45 years with preexisting cardiovascular disease), PMI was defined as an absolute increase in high-sensitivity cTnT (hs-cTnT) concentration of ≥14 ng/L (the 99th percentile) above the preoperative concentration. Perioperative myocardial infarction/injury was centrally adjudicated by two independent cardiologists using serial measurements of hs-cTnT. Using logistic regression, three models were derived: Model 1 including patient- and procedure-related information, Model 2 adding routinely available laboratory values, and Model 3 further adding preoperative hs-cTnT concentration. Models were also compared vs. preoperative hs-cTnT alone. The findings were validated in two independent cohorts. Among 6944 patients, PMI occurred in 1058 patients (15.2%). The predictive accuracy as quantified by the area under the receiver operating characteristic curve was 0.73 [95% confidence interval (CI) 0.71-0.74] for Model 1, 0.75 (95% CI 0.74-0.77) for Model 2, 0.79 (95% CI 0.77-0.80) for Model 3, and 0.74 for hs-cTnT alone. Model 3 included 10 preoperative variables: age, body mass index, known coronary artery disease, metabolic equivalent >4, risk of surgery, emergency surgery, planned duration of surgery, haemoglobin, platelet count, and hs-cTnT. These findings were confirmed in both independent validation cohorts (n = 722 and n = 966). CONCLUSION: Preoperative cTn adds incremental value above patient- and procedure-related variables as well as routine laboratory variables in the prediction of PMI.

A systematic outbreak investigation of SARS-CoV-2 transmission clusters in a tertiary academic care center.

BACKGROUND: We sought to decipher transmission pathways in healthcare-associated infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within our hospital by epidemiological work-up and complementary whole genome sequencing (WGS). We report the findings of the four largest epidemiologic clusters of SARS-CoV-2 transmission occurring during the second wave of the pandemic from 11/2020 to 12/2020. METHODS: At the University Hospital Basel, Switzerland, systematic outbreak investigation is initiated at detection of any nosocomial case of SARS-CoV-2 infection, as confirmed by polymerase chain reaction, occurring more than five days after admission. Clusters of nosocomial infections, defined as the detection of at least two positive patients and/or healthcare workers (HCWs) within one week with an epidemiological link, were further investigated by WGS on respective strains. RESULTS: The four epidemiologic clusters included 40 patients and 60 HCWs. Sequencing data was available for 70% of all involved cases (28 patients and 42 HCWs), confirmed epidemiologically suspected in house transmission in 33 cases (47.1% of sequenced cases) and excluded transmission in the remaining 37 cases (52.9%). Among cases with identical strains, epidemiologic work-up suggested transmission mainly through a ward-based exposure (24/33, 72.7%), more commonly affecting HCWs (16/24, 66.7%) than patients (8/24, 33.3%), followed by transmission between patients (6/33, 18.2%), and among HCWs and patients (3/33, 9.1%, respectively two HCWs and one patient). CONCLUSIONS: Phylogenetic analyses revealed important insights into transmission pathways supporting less than 50% of epidemiologically suspected SARS-CoV-2 transmissions. The remainder of cases most likely reflect community-acquired infection randomly detected by outbreak investigation. Notably, most transmissions occurred between HCWs, possibly indicating lower perception of the risk of infection during contacts among HCWs.

Are there cervical spine findings at MR imaging that are specific to acute symptomatic whiplash injury? A prospective controlled study with four experienced blinded readers.

PURPOSE: To compare the magnetic resonance (MR) imaging findings in patients with acute whiplash injury with those in matched control subjects. MATERIALS AND METHODS: In a prospective multicenter controlled study, from 2005 to 2008, 100 consecutive patients underwent 1.5-T MR imaging examinations of the cervical spine within 48 hours after a motor vehicle accident. Findings in these patients were compared in a blinded fashion with those in 100 age- and sex-matched healthy control subjects. Four blinded independent readers assessed the presence of occult vertebral body and facet fractures, vertebral body and facet contusions, intervertebral disk herniations, ligamentum nuchae strains, ligamentum nuchae tears, muscle strains or tears, and perimuscular fluid. Accuracy (as compared with clinical findings) and interobserver reliability were calculated. RESULTS: Accuracy of MR imaging and interreader reliability were generally poor (sensitivity, 0.328; specificity, 0.728; positive and negative likelihood ratios, 1.283 and 1.084, respectively). MR imaging findings significantly associated with whiplash injuries were occult fracture (P<.01), bone marrow contusion of the vertebral body (P=.01), muscle strain (P<.01) or tear (P<.01), and the presence of perimuscular fluid (P<.01). While 10 findings thought to be specific for whiplash trauma were significantly (P<.01) more frequent in patients (507 observations), they were also regularly found in healthy control subjects (237 observations). There were no serious occult injuries that required immediate therapy. CONCLUSION: MR imaging at 1.5 T reveals only limited evidence of specific changes to the cervical spine and the surrounding tissues in patients with acute symptomatic whiplash injury compared with healthy control subjects.

Cardiovascular imaging following perioperative myocardial infarction/injury.

Patients developing perioperative myocardial infarction/injury (PMI) have a high mortality. PMI work-up and therapy remain poorly defined. This prospective multicenter study included high-risk patients undergoing major non-cardiac surgery within a systematic PMI screening and clinical response program. The frequency of cardiovascular imaging during PMI work-up and its yield for possible type 1 myocardial infarction (T1MI) was assessed. Automated PMI detection triggered evaluation by the treating physician/cardiologist, who determined selection/timing of cardiovascular imaging. T1M1 was considered with the presence of a new wall motion abnormality within 30 days in transthoracic echocardiography (TTE), a new scar or ischemia within 90 days in myocardial perfusion imaging (MPI), and Ambrose-Type II or complex lesions within 7 days of PMI in coronary angiography (CA). In patients with PMI, 21% (268/1269) underwent at least one cardiac imaging modality. TTE was used in 13% (163/1269), MPI in 3% (37/1269), and CA in 5% (68/1269). Cardiology consultation was associated with higher use of cardiovascular imaging (27% versus 13%). Signs indicative of T1MI were found in 8% of TTE, 46% of MPI, and 63% of CA. Most patients with PMI did not undergo any cardiovascular imaging within their PMI work-up. If performed, MPI and CA showed high yield for signs indicative of T1MI.Trial registration: https://clinicaltrials.gov/ct2/show/NCT02573532 .

Fibroblast growth factor 2 and platelet-derived growth factor, but not platelet lysate, induce proliferation-dependent, functional class II major histocompatibility complex antigen in human mesenchymal stem cells.

OBJECTIVE: To document the specificity and the mechanism of induction of a novel class II major histocompatibility complex (MHC) antigen by mitogenic growth factors in human mesenchymal stem cells (MSCs) expanded in vitro for translational applications. METHODS: Expression of class II MHC molecules was measured in human MSCs and differentiated cells expanded in the presence of fibroblast growth factor 2 (FGF-2), platelet-derived growth factor BB (PDGF-BB), human platelet lysate, or interferon-γ (IFNγ). The roles of cell proliferation and growth factor-induced signaling pathways were investigated as well as the class II MHC assembly machinery and functional capacity. RESULTS: FGF-2 and, to a lesser extent, PDGF-BB induced in adult human MSCs the expression of HLA-DR (normally induced by inflammatory cytokines), which was able to stimulate CD4+ T cells via superantigen binding. In contrast to IFNγ, FGF induced HLA-DR expression only in human MSCs proliferating under its mitogenic effect and not in mouse MSCs or in differentiated human cells. Although it induced cell proliferation, human platelet lysate did not cause HLA-DR expression in human MSCs. HLA-DR expression occurred following FGF-specific binding to its receptor(s), mainly FGF receptor 1, without inducing IFNγ or tumor necrosis factor α expression. Both MAPK/ERK-1/2 and phosphatidylinositol 3-kinase/Akt controlled cell proliferation and HLA-DR expression, but only MAPK/ERK-1/2 controlled the induction of the class II MHC transcription activator protein CIITA, the major determinant of HLA-DR transcription. CONCLUSION: The induction of functional HLA-DR in proliferating progenitor MSCs is a property of human MSCs that have been expanded with mitogenic growth factors. This has potential biologic significance in the regulation and/or protection of progenitor cell subpopulations under sustained mitogenic proliferation and needs to be taken into account when expanding MSCs for use in in vivo applications.

Implant removal after posterior stabilization of the thoraco-lumbar spine.

INTRODUCTION: Implant removal because of pain after posterior fusion in the thoracic and lumbar spine is a widely performed operation. We conducted a retrospective study to examine whether patients benefit from implant removal. PATIENTS AND METHODS: 57 patients (29 males, 28 females, mean age 46.5 years) who have undergone removal of pedicle screws because of pain and discomfort were interviewed 6-24 months postoperatively. Fracture was the initial diagnosis in 40% of the patients and degenerative spine disease in 58%. The following factors were evaluated: patient satisfaction and postoperative outcome, patients' native language and psychological background, operative data, hospital stay and complications. RESULTS: Pain decreased significantly from 62 to 48 on visual analogue scale postoperatively. Complications occurred in five patients (8.8%). 36 patients (61%) stated they had some benefit from the operation, but only seven patients (12%) were free of pain completely. 36 patients (63%) would undergo the same procedure again. Outcome in the subgroup of foreigners was significantly worse, though the psychological background did not affect the outcome. Preoperative diagnostic infiltration was helpful in 9 of 13 patients. CONCLUSION: Removal of pedicle screws because of back pain may be effective, but complete remission of symptoms could be achieved in only 12% of patients. However, 63% of patients would undergo hardware removal again. Preoperative diagnostic infiltration can help to predict the outcome but results are inconsistent. Communication difficulties may worsen the outcome. Surgeons should consider these results when planning implant removal and patients should be informed thoroughly to avoid too high expectations.

Incidence of major adverse cardiac events following non-cardiac surgery.

AIMS: Major adverse cardiac events (MACE) triggered by non-cardiac surgery are prognostically important perioperative complications. However, due to often asymptomatic presentation, the incidence and timing of postoperative MACE are incompletely understood. METHODS AND RESULTS: We conducted a prospective observational study implementing a perioperative screening for postoperative MACE [cardiovascular death (CVD), acute heart failure (AHF), haemodynamically relevant arrhythmias, spontaneous myocardial infarction (MI), and perioperative myocardial infarction/injury (PMI)] in patients at increased cardiovascular risk (≥65 years OR ≥45 years with history of cardiovascular disease) undergoing non-cardiac surgery at a tertiary hospital. All patients received serial measurements of cardiac troponin to detect asymptomatic MACE. Among 2265 patients (mean age 73 years, 43.4% women), the incidence of MACE was 15.2% within 30 days, and 20.6% within 365 days. CVD occurred in 1.2% [95% confidence interval (CI) 0.9-1.8] and in 3.7% (95% CI 3.0-4.5), haemodynamically relevant arrhythmias in 1.2% (95% CI 0.9-1.8) and in 2.1% (95% CI 1.6-2.8), AHF in 1.6% (95% CI 1.2-2.2) and in 4.2% (95% CI 3.4-5.1), spontaneous MI in 0.5% (95% CI 0.3-0.9) and in 1.6% (95% CI 1.2-2.2), and PMI in 13.2% (95% CI 11.9-14.7) and in 14.8% (95% CI 13.4-16.4) within 30 days and within 365 days, respectively. The MACE-incidence was increased above presumed baseline rate until Day 135 (95% CI 104-163), indicating a vulnerable period of 3-5 months. CONCLUSION: One out of five high-risk patients undergoing non-cardiac surgery will develop one or more MACE within 365 days. The risk for MACE remains increased for about 5 months after non-cardiac surgery. TRIAL REGISTRATION: https://www.clinicaltrials.gov. Unique identifier: NCT02573532.

Inertial Measurement Unit-Assisted Implantation of Pedicle Screws in Combination With an Intraoperative 3-Dimensional/2-Dimensional Visualization of the Spine.

BACKGROUND: Inertial measurement units (IMUs) are microelectromechanical systems used to track orientation and motion. OBJECTIVE: To use instruments mounted with IMUs in combination with a 3- and 2-dimensional (3D/2D) rendering of the computed-tomography scan (CT) to guide implantation of pedicle screws. METHODS: Pedicle screws were implanted from T1 to S1 in 2 human cadavers. A software application enabled the surgeon to select the starting points and trajectories on a 3D/2D image of the spine, then locate these starting points on the exposed spine and apply the IMU-mounted instruments to reproduce the trajectories. The position of the screws was evaluated on the postoperative CT scan. RESULTS: A total of 72 pedicle screws were implanted. Thirty-seven (77%) of the thoracic screws were within the pedicle (Heary I), 7 (15%) showed a lateral breach of the pedicle, and 4 (8%) violated the anterior or lateral vertebral body (Heary III). In the lumbar spine and S1, 21 screws (88%) were within the pedicle (Gertzbein 0), 2 (8%) screws had a pedicle wall breach < 2 mm (Gertzbein 1), and 1 > 2 to < 4 mm (Gertzbein 2). In the second cadaver, the position was compared to the intraoperatively shown virtual position. The median offset was 3°(mean 3° ± 2°, variance 5, range 0°-9°) in the sagittal plane and 3° (mean 4° ± 3°, variance 9, range 0°-12°) in the axial plane. CONCLUSION: IMU-assisted implantation of pedicle screws combined with an intraoperative 3D/2D visualization of the spine enabled the surgeon to precisely implant pedicle screws on the exposed spine.

Outcome of Spinal Surgery in Patients Older Than Age 90 Years.

BACKGROUND: Increased life expectancy has led to indications for spine surgery in patients older than 90 years, but data on associated risks and outcome are lacking. METHODS: Indication, type of surgery, complications, functional outcome, and mortality were retrospectively collected from all patients aged 90 years or older operated between 2006 and 2016 at the University Hospital Basel, Switzerland. RESULTS: Sixty-nine patients were included, of which 55% had degenerative, 36% traumatic, and 9% other pathologies. Most surgeries (84%) were performed electively and 16% as emergencies. More than a third (36%) of elective and 58% of emergency surgeries required stabilization. The complication rate was 54% in the elective surgery group (ELSG) and 125% in the emergency surgery group (EMSG). Stabilization (P = 0.006) and emergency surgeries (P = 0.032) were significant risk factors for experiencing complications. Six weeks after surgery, 80% of the patients reported symptomatic improvement. More than half (58%) of the patients in the ELSG reached their specific median life expectancy, compared with 38% in the EMSG. Seventeen percent of patients in the EMSG versus 0% in the ELSG died in the first 3 months after surgery. In the nonstabilized group, 67% of the patients reached their median life expectancy, compared with 38% of the stabilized group. CONCLUSIONS: Elective spinal surgery in patients older than 90 years of age does not reduce life expectancy and has a good functional outcome for well-selected patients, whereas emergency surgery and stabilization surgery in this age group are associated with a high rate of complications and higher mortality.

Direct Oral Anticoagulants in Patients Undergoing Spine Surgery.

OBJECTIVE: Despite increasing use of direct oral anticoagulants (DOACs), guidelines for their perioperative use in spine surgery are still lacking. The main goal of our study was to analyze the occurrence of postoperative bleeding events and possible confounders in patients treated with DOACs who undergo spine surgery. METHODS: Of 2777 patients undergoing spine surgery at our institution, 82 (2.9%) were treated with DOACs. The primary endpoint was postoperative bleeding events. Secondary outcome measures were postoperative thromboembolic events and anemia, hematologic findings, perioperative packed red blood cell substitution, operative time, hospital length of stay, morbidity, and mortality. Subanalysis of possible confounders affecting the rates of bleeding was also performed. Additionally, correlation of bleeding event rates and preoperative and postoperative discontinuation of DOACs was analyzed. RESULTS: Overall postoperative bleeding events rate was 4.9% (n = 4). Preoperative DOAC discontinuation time of <24 hours increased significantly the rate of perioperative packed red blood cell substitution (P = 0.007). Treatment with concomitant blood thinners showed a trend toward higher incidence of bleeding events (P = 0.066), whereas pre-existing kidney failure increased significantly rates of postoperative anemia (P = 0.014). The rate of postoperative thromboembolic events was 4.9% (n = 4); all events occurred with DOAC resumption >72 hours postoperatively. CONCLUSIONS: Short preoperative discontinuation time of DOACs, even <24 hours, may be justified, considering an increased risk of perioperative packed red blood cell substitution. Care should be taken with patients treated with concomitant blood thinners and patients with pre-existing kidney disease. Postoperative DOAC resumption >72 hours may increase risk of thromboembolic events.

Reconstruction of Spinal Soft Tissue Defects With Perforator Flaps From the Paraspinal Region.

BACKGROUND/AIM: Reconstruction of spinal soft tissue defects is challenging, especially when neural structures or prosthetic material are exposed. They should be covered with well-vascularized tissue such as paraspinal perforator flaps. MATERIALS AND METHODS: This is a retrospective study of soft tissue reconstructions with paraspinal perforator flaps from 2011 to 2018. The technique is described and risk factors for poor wound healing were assessed. Postoperative complications are reported. RESULTS: Twenty patients with a mean age of 63.65 years were included. Defects had an average size of 47 cm2 and were mainly located in the lumbosacral region (9 patients). Twelve patients suffered from infection following spinal stabilization, seven of whom were diagnosed with osteomyelitis, two patients presented with pressure sore and one patient experienced wound dehiscence. One partial flap necrosis with a lumbar defect occurred, which required revision surgery. No total flap loss occurred. Stable, closed wounds were achieved at their final follow-up. CONCLUSION: Perforator paraspinal flaps are suitable for immediate reconstruction of spinal defects.