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.

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.

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 .

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.

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.

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.

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.

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.

Epineural adipose-derived stem cell injection in a sciatic rodent model.

BACKGROUND: The aim was to evaluate the regenerative effect of epineural injection of rat ASCs (rASCs) in three different settings of acute and chronic compression in a rat sciatic nerve model. METHODS: Acute compression (60 s) with a vessel clamp over a distance of 1 mm (group 1) or 10 mm (group 2), as well as chronic compression with a permanent remaining, nonabsorbable polymeric clip over a distance of 1 mm (group 3) was performed. Depending on the group, either 5 × 106 rASCs or the same volume (25 µl) of culture medium (CM) was injected with a 30G needle in the epineurium at the time of compression. Outcome measures were functional gait evaluations, imaging analysis, histomorphometric analyses, and muscle weight. RESULTS: The rats in group 2 had a better function than those with group 1 at one and especially at 2 weeks. After 4 weeks however, almost all rats were close to a normal function. There was a similar Muscle Weight Ratio (MWR) after 2 weeks in all groups, whereas after 4 weeks, the MWR in group 3 was lower compared with group 1 and 2. Histomorphometric analysis showed a better myelination in group 1 & 2 compared to group 3 after 4 weeks. ASCs have a beneficial effect on myelin thickness (G-Ratio). CONCLUSIONS: We successfully evaluated the regenerative effect of epineural injection of rASCs in three different settings of acute and chronic compression. However, there were no significant differences in outcomes between the ASC-treated groups and control groups.

Thalidomide Embryopathy as Possible Cause of Anterior Sacral Meningocele: A Case Report.

A 54-year-old male presented with a sudden burning sensation during urination and left flank pain. Apart from having congenital facial palsy and malformation of the inner right ear that was linked to thalidomide embryopathy, the patient has always been in good health. Urine examination showed the presence of a urinary tract infection. An abdominal ultrasound revealed a large cyst in the lower abdomen, which on MRI corresponded to a large anterior sacral meningocele (ASM) with sacral agenesis at S1/S2. After antibiotic treatment and the spontaneous passage of a kidney stone, the symptoms resolved. This suggests that the patient's acute symptoms were caused by the urolithiasis and not the ASM. Thalidomide is teratogenic between days 17 and 30 after conception. The neural tube closes between days 20 and 36, therefore, thalidomide embryopathy was the possible cause of ASM in this patient. Birth Defects Research 109:1390-1392, 2017.© 2017 Wiley Periodicals, Inc.

Inertial Measurement Unit-Assisted Implantation of Thoracic, Lumbar, and Sacral Pedicle Screws Improves Precision of a Freehand Technique.

OBJECTIVE: A method applying inertial measurement units (IMUs) was developed to implant pedicle screws in the thoracic and lumbosacral spine. This was compared with a freehand technique. METHODS: The study was done on 9 human cadavers. For each cadaver, a preoperative computed tomography (CT) scan was performed to measure the axial and sagittal tilt angles of the screw trajectories from T1 to S1. After the entry points were defined on the exposed spine, the IMU-equipped pedicle finder and screwdriver were used to reproduce these tilt angles and implant half of the screws. The other half was implanted with a freehand technique. Fluoroscopy was not used. The screw trajectories were analyzed on postoperative CTs. RESULTS: A hundred and sixty-two screws were placed with use of the IMUs and 162 screws were implanted by freehand. The IMU-guided technique matched the planned trajectories significantly better than the freehand technique (axial tilt P < 0.001, sagittal tilt P < 0.001). With IMU assistance, the mean offsets between the planned and postoperatively measured tilt angles of the screws were 3.3 degrees ± 3.5 degrees for the axial plane (median 2 degrees, range 0-23 degrees) and 3.4 degrees ± 3 degrees for the sagittal plane (median 3 degrees, range 0-13 degrees). For the freehand technique, the mean offsets between the planned and postoperatively measured tilt angles of the screws were 5.6 degrees ± 4.5 degrees for the axial plane (median 5 degrees, range 0-31 degrees) and 6.7 degrees ± 5.4 degrees for the sagittal plane (median 6 degrees, range 0-33 degrees). CONCLUSIONS: IMU-assisted implantation of pedicle screws may enhance the performance of a freehand technique in the thoracic and lumbosacral spine.

Notochordal cell-derived conditioned medium protects human nucleus pulposus cells from stress-induced apoptosis.

BACKGROUND CONTEXT: Degenerative disc disease (DDD) remains without an effective therapy and presents a costly burden to society. PURPOSE: Based upon prior reports concerning the effects of notochordal cell-conditioned medium (NCCM) on disc cells, we performed a proof of principle study to determine whether NCCM could reduce cytotoxic stress-induced apoptosis in human disc nucleus pulposus (NP) cells. STUDY DESIGN/SETTING: This is an "in vitro" fundamental or basic science study. METHODS: Nucleus pulpous cells derived from 15 patients undergoing spinal surgery were treated with interleukin (IL)-1ß and Fas ligand or etoposide in the presence of NCCM. We determined pro- or antiapoptotic events using activated caspase assays and determined genomic regulation of apoptosis using polymerase chain reaction arrays validated using Western blotting methods. We interrogated cellular apoptotic regulation using JC-1 dye and flow cytometry and performed enzyme-linked immunosorbent assays to evaluate NP inflammatory cytokine secretion. RESULTS: Notochordal cell-conditioned medium inhibits cytotoxic stress-induced caspase-9 and -3/7 activities and maintains the mitochondrial membrane potential in human NP cells, thereby suppressing the intrinsic apoptotic pathway. Gene expression analysis revealed the X-linked inhibitor of apoptosis protein as a key player responsible for evading etoposide-induced apoptosis in the presence of NCCM, and we verified these data using Western blotting. Enzyme-linked immunosorbent assay results revealed distinct differences in IL-6 and IL-8 secretions by NP cells in response to etoposide in the presence of NCCM. CONCLUSIONS: Here we demonstrate for the first time that NCCM reduces cytotoxic stress-induced apoptosis in human NP cells. Soluble factors present in NCCM could be harnessed for the development of novel therapeutics for the treatment of DDD.

Spontaneous In Vivo Chondrogenesis of Bone Marrow-Derived Mesenchymal Progenitor Cells by Blocking Vascular Endothelial Growth Factor Signaling.

: Chondrogenic differentiation of bone marrow-derived mesenchymal stromal/stem cells (MSCs) can be induced by presenting morphogenetic factors or soluble signals but typically suffers from limited efficiency, reproducibility across primary batches, and maintenance of phenotypic stability. Considering the avascular and hypoxic milieu of articular cartilage, we hypothesized that sole inhibition of angiogenesis can provide physiological cues to direct in vivo differentiation of uncommitted MSCs to stable cartilage formation. Human MSCs were retrovirally transduced to express a decoy soluble vascular endothelial growth factor (VEGF) receptor-2 (sFlk1), which efficiently sequesters endogenous VEGF in vivo, seeded on collagen sponges and immediately implanted ectopically in nude mice. Although naïve cells formed vascularized fibrous tissue, sFlk1-MSCs abolished vascular ingrowth into engineered constructs, which efficiently and reproducibly developed into hyaline cartilage. The generated cartilage was phenotypically stable and showed no sign of hypertrophic evolution up to 12 weeks. In vitro analyses indicated that spontaneous chondrogenic differentiation by blockade of angiogenesis was related to the generation of a hypoxic environment, in turn activating the transforming growth factor-ß pathway. These findings suggest that VEGF blockade is a robust strategy to enhance cartilage repair by endogenous or grafted mesenchymal progenitors. This article outlines the general paradigm of controlling the fate of implanted stem/progenitor cells by engineering their ability to establish specific microenvironmental conditions rather than directly providing individual morphogenic cues. SIGNIFICANCE: Chondrogenic differentiation of mesenchymal stromal/stem cells (MSCs) is typically targeted by morphogen delivery, which is often associated with limited efficiency, stability, and robustness. This article proposes a strategy to engineer MSCs with the capacity to establish specific microenvironmental conditions, supporting their own targeted differentiation program. Sole blockade of angiogenesis mediated by transduction for sFlk-1, without delivery of additional morphogens, is sufficient for inducing MSC chondrogenic differentiation. The findings represent a relevant step forward in the field because the method allowed reducing interdonor variability in MSC differentiation efficiency and, importantly, onset of a stable, nonhypertrophic chondrocyte phenotype.

Notochordal cell conditioned medium (NCCM) regenerates end-stage human osteoarthritic articular chondrocytes and promotes a healthy phenotype.

BACKGROUND: Notochordal cell conditioned medium (NCCM) derived from non-chondrodystrophic dogs has pro-anabolic and anti-catabolic effects upon nucleus pulposus (NP) cells. Here, for the first time, we assessed the ability of NCCM to influence the production of extracellular matrix and inflammatory proteins by healthy and osteoarthritic human chondrocytes within engineered cartilage tissues. We hypothesized that, similar to its action on NP cells, NCCM exerts metabolic and anti-catabolic effects on human articular chondrocytes and has the potential to significantly counteract inflammatory mediators. METHODS: Chondrocytes from nine non-osteoarthritic patients and from six osteoarthritic (OA) donors at the time of total knee arthroplasty were chondro-differentiated in pellets for 2 weeks. Non-OA pellets were exposed for 72 hours to IL-1ß/TNF-α and then cultured up to 14 days in 2 % FBS-supplemented NCCM or 2 % FBS-supplemented medium (control (ctr)). OA pellets were cultured in NCCM or ctr medium without pro-inflammatory treatment. Tissues after each culture phase were analyzed biochemically (GAG/DNA), (immuno-) histologically (collagen I, II and GAG) and by Western blotting. Supernatants were analyzed by ELISA. RESULTS: Response to NCCM was age and disease dependent with healthy chondrocyte pellets (from donors >55 years of age) recovering their glycosaminoglycan (GAG) contents to baseline levels only with NCCM. OA pellets treated with NCCM significantly increased GAG content (1.8-fold) and levels of hyaluronic acid link protein (HAPLN), fibromodulin and SOX-9. The catabolic proteins (matrix metalloproteinase (MMP)-3 and MMP-13) and pro-inflammatory enzyme levels (cyclooxygenase-2 (COX-2)) were markedly reduced and there was significantly reduced secretion of pro-inflammatory chemokines (IL-6 and IL-8). CONCLUSIONS: NCCM restores cartilage matrix production of end-stage human OA chondrocytes towards a healthy phenotype and suppresses the production of inflammatory mediators. Harnessing the necessary and sufficient factors within NCCM that confers chondroprotection and regenerative effects could lead to a minimally invasive agent for treatment of degenerative and inflammatory joint diseases.

Union Rate and Complications in Spine Fusion with Recombinant Human Bone Morphogenetic Protein-7: Systematic Review and Meta-Analysis.

Study Design Systematic review and meta-analysis. Objective The objective of this meta-analysis was to evaluate the current best evidence to assess effectiveness and safety of recombinant human bone morphogenetic protein-7 (rhBMP-7) as a biological stimulant in spine fusion. Methods Studies were included if they reported on outcomes after spine fusion with rhBMP-7. The data was synthesized using Mantel-Haenszel pooled risk ratios (RRs) with 95% confidence intervals (CIs). Main end points were union rate, overall complications, postoperative back and leg pain, revision rates, and new-onset cancer. Results Our search produced 796 studies, 6 of which were eligible for inclusion. These studies report on a total of 442 patients (328 experimental, 114 controls) with a mean age of 59 ± 11 years. Our analysis showed no statistically significant differences in union rates (RR 0.97, 95% CI 0.84 to 1.11, p = 0.247), overall complications (RR 0.92, 95% CI 0.71 to 1.20, p = 0.545), postoperative back and leg pain (RR 1.03, 95% CI 0.48 to 2.19, p = 0.941), or revision rate (RR 0.81, 95% CI 0.47 to 1.40, p = 0.449). There was a mathematical indicator of increased tumor rates, but with only one case, the clinical meaningfulness of this finding is questionable. Conclusion We were not able to find data in support of the use of rhBMP-7 for spine fusion. We found no evidence for increased complication or revision rates with rhBMP-7. On the other hand, we also found no evidence in support of improved union rates.

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.

Management of Incidental Dural Tear During Lumbar Spine Surgery. To Suture or Not to Suture?

OBJECTIVE: Incidental durotomy (ID) during lumbar spine surgery is a frequent complication of growing clinical relevance as the number and complexity of spinal procedures increases. Yet, there is still a lack of guidelines for the treatment of ID with a large heterogeneity of established surgical techniques. The aim of this study was to investigate the efficacy of dural suturing in patients having ID during degenerative lumbar spine surgery, compared with other dural closure techniques. METHODS: Of 1173 consecutive patients undergoing degenerative lumbar spine surgery from July 2013 to March 2015, in 64 (5.4%) patients 69 (5.8%) IDs occurred. The patients were divided into 3 groups depending on the dural closure technique used: group A, sole dural suture (n = 12, 19%); group B, patch only (TachoSil and/or muscle and/or fat) (n = 22, 32%); group C, dural suture in combination with a patch (n = 34, 49%). The primary end point was revision surgery caused by complications of cerebrospinal fluid leakage after 6 weeks. The secondary end points were operation time and hospitalization time, as well as surgical morbidity. RESULTS: The 3 groups showed no significant difference in rates of revision surgery (group A: n = 1, 1.4%; group B: n = 4, 5.8%; group C: n = 3; 4.3%; P = 0.5). Furthermore, no significant difference for hospitalization time, operation time, and clinical outcome was found. Extent of ID, American Society of Anesthesiology score, postoperative immobilization, and insertion of a drainage tube were not associated with higher rates of revision surgery. Applying suction once a drainage tube was placed was found to be a significant risk factor for revision surgery (P = 0.003). Furthermore, patients undergoing revision surgery had a significantly higher body mass index (33 kg/m(2) vs. 26.37 kg/m(2); P = 0.006; odds ratio 1.252; P = 0.004). CONCLUSIONS: Based on our results, the dural closure technique after ID does not seem to influence revision surgery rates due to cerebrospinal fluid leakage and its complications. Further prospective randomized studies are needed to confirm our results.

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.