Outcomes of decompressive craniectomy for large territory cerebral infarction with and without prior reperfusion: a multicentre retrospective review.

PURPOSE: Reperfusion therapy has greatly improved outcomes of ischaemic stroke but remains associated with haemorrhagic conversion and early deterioration in a significant proportion of patients. Outcomes in terms of function and mortality are mixed and the evidence for decompressive craniectomies (DC) in this context remains sparse. We aim to investigate the clinical efficacy of DC in this group of patients compared to those without prior reperfusion therapy. METHODS: A multicentre retrospective study was conducted between 2005 and 2020, and all patients with DC for large territory infarctions were included. Outcomes in terms of inpatient and long-term modified Rankin scale (mRS) and mortality were assessed at various time points and compared using both univariable and multivariable analyses. Favourable mRS was defined as 0-3. RESULTS: There were 152 patients included in the final analysis. The cohort had a mean age of 57.5 years and median Charlson comorbidity index of 2. The proportion of preoperative anisocoria was 15.1%, median preoperative Glasgow coma scale was 9, the ratio of left-sided stroke was 40.1%, and ICA infarction was 42.8%. There were 79 patients with prior reperfusion and 73 patients without. After multivariable analysis, the proportion of favourable 6-month mRS (reperfusion, 8.2%; no reperfusion, 5.4%) and 1-year mortality (reperfusion, 26.7%; no reperfusion, 27.3%) were similar in both groups. Subgroup analysis of thrombolysis and/or thrombectomy against no reperfusion was also unremarkable. CONCLUSION: Reperfusion therapy prior to DC performed for large territory cerebral infarctions does not affect the functional outcome and mortality in a well-selected patient population.

Characteristics and Postoperative Outcomes for High Cervical versus Subaxial Cervical Intradural Extramedullary Tumors: A Multicenter Study.

BACKGROUND: High cervical intradural extramedullary tumors are uncommon. Their relationship to surrounding neural structures and vertebral arteries makes surgical excision challenging. No previous studies have compared high cervical to subaxial cervical intradural extramedullary spinal tumors to elucidate their unique characteristics and surgical outcomes. METHODS: We performed a retrospective study in which patients who underwent excision of a cervical intradural extramedullary tumor were divided into a high cervical group and a subaxial cervical group. Variables included sex, age, Charlson Comorbidity Index, volume, laterality, preoperative weakness, use of neuromonitoring and drains, instrumented fusion, complications, length of stay, histology, discharge location, recurrence, and duration of follow-up. Variables were compared between the 2 groups. Limb power and Nurick classification were charted preoperatively, at discharge, and at 6 months to plot their recovery trajectory. RESULTS: Eighty-four patients with a total of 90 tumors were enrolled, including 40 patients in the high cervical group and 44 patients in the subaxial spine group. More patients with neurofibromas (P = 0.011) and bilateral tumors (P = 0.044) were in the high cervical group. A greater prevalence of neurofibromatosis type 1 was significant for bilateral high cervical tumors (P = 0.033). More patients in the subaxial group had instrumented fusion (P = 0.045). More patients in the high cervical group had improvement in limb power (P = 0.025) and Nurick classification (P = 0.0001) postoperatively before discharge. By 6 months, both groups had similar recovery. No mortality was attributable to surgery in either group. CONCLUSION: High cervical intradural extramedullary spine tumors have more bilateral tumors associated with neurofibromatosis type 1. Despite the challenging anatomy, surgical resection is safe with good outcomes in this group.

Clinical Outcomes of 3D-Printed Bioresorbable Scaffolds for Bone Tissue Engineering-A Pilot Study on 126 Patients for Burrhole Covers in Subdural Hematoma.

Burrhole craniostomy is commonly performed for subdural hematoma (SDH) evacuation, but residual scalp depressions are often cosmetically suboptimal for patients. OsteoplugTM, a bioresorbable polycaprolactone burrhole cover, was introduced by the National University Hospital, Singapore, in 2006 to cover these defects, allowing osseous integration and vascular ingrowth. However, the cosmetic and safety outcomes of OsteoplugTM-C-the latest (2017) iteration, with a chamfered hole for subdural drains-remain unexplored. Data were collected from a single institution from April 2017 to March 2021. Patient-reported aesthetic outcomes (Aesthetic Numeric Analog (ANA)) and quality of life (EQ-5D-3L including Visual Analog Scale (VAS)) were assessed via telephone interviews. Clinical outcomes included SDH recurrence, postoperative infections, and drain complications. OsteoplugTM-C patients had significantly higher satisfaction and quality of life compared to those without a burrhole cover (ANA: 9 [7, 9] vs. 7 [5, 8], p = 0.019; VAS: 85 [75, 90] vs. 70 [50, 80], p = 0.021), and the absence of a burrhole cover was associated with poorer aesthetic outcomes after multivariable adjustment (adjusted OR: 4.55, 95% CI: 1.09-22.68, p = 0.047). No significant differences in other clinical outcomes were observed between OsteoplugTM-C, OsteoplugTM, or no burrhole cover. Our pilot study supports OsteoplugTM-C and its material polycaprolactone as suitable adjuncts to burrhole craniostomy, improving cosmetic outcomes while achieving comparable safety outcomes.

Decompressive craniectomy for internal carotid artery and middle carotid artery infarctions: a long-term comparative outcome study.

OBJECTIVE: Malignant internal carotid artery (ICA) infarction is an entirely different disease entity when compared with middle cerebral artery (MCA) infarction. Because of an increased area of infarction, it is assumed to have a poorer prognosis; however, this has never been adequately investigated. Decompressive craniectomy (DC) for malignant MCA infarction has been shown to improve mortality rates in several randomized controlled trials. Conversely, aggressive surgical decompression for ICA infarction has not been recommended. The authors sought to compare the functional outcomes and survival between patients with ICA infarctions and those with MCA infarctions after DC in the largest series to date to investigate this assumption. METHODS: A multicenter retrospective review of 154 consecutive DCs for large territory cerebral infarctions performed from 2005 to 2020 were analyzed. Patients were divided into ICA and MCA groups depending on the territory of infarction. Variables, including age, sex, medical comorbidities, laterality of the infarction, preoperative neurological status, primary stroke treatment, and the time from stroke onset to DC, were recorded. Univariable and multivariable analyses were performed for the clinical exposures for functional outcomes (modified Rankin Scale [mRS] score) on discharge and at the 1- and 6-month follow-ups, and for mortality, both inpatient and at the 1-year follow-up. A favorable mRS score was defined as 0-2. RESULTS: There were 67 patients (43.5%) and 87 patients (56.5%) in the ICA and MCA groups, respectively. Univariable analysis showed that the ICA group had a comparably favorable mRS (OR 0.15 [95% CI 0.18-1.21], p = 0.077). Inpatient mortality (OR 1.79 [95% CI 0.79-4.03], p = 0.16) and 1-year mortality (OR 2.07 [95% CI 0.98-4.37], p = 0.054) were comparable between the groups. After adjustment, a favorable mRS score at 6 months (OR 0.17 [95% CI 0.018-1.59], p = 0.12), inpatient mortality (OR 1.02 [95% CI 0.29-3.57], p = 0.97), and 1-year mortality (OR 0.94 [95% CI 0.41-2.69], p = 0.88) were similar in both groups. The overall survival, plotted using the Cox proportional hazard regression, did not show a significant difference between the ICA and MCA groups (HR 0.581). CONCLUSIONS: Unlike previous smaller studies, this study found that patients with malignant ICA infarction had a functional outcome and survival that was similar to those with MCA infarction after DC. Therefore, DC can be offered for malignant ICA infarction for life-saving purposes with limited functional recovery.

The "Blush" Sign on Computed Tomography Angiography is an Independent Predictor of Hematoma Progression in Primary Hypertensive Hemorrhage.

BACKGROUND AND PURPOSE: Hypertension is an important etiology of intracerebral hemorrhage (ICH) in neurosurgical practice. Contrast extravasation on computed tomography angiography, known as the "spot sign", has been described as an independent predictor of hematoma progression and clinical deterioration. However, its role in hypertensive ICH alone has not been determined and is the primary aim of this study. MATERIALS AND METHODS: A retrospective review was carried out of patients with hypertensive ICH admitted to our institution between May 2014 and December 2016. Evaluation of the neuroimaging studies of these patients revealed two distinct morphologies, "spot" and "blush" sign. These distinct signs and covariates were tested for association with hematoma expansion and mortality using multivariate logistic regression. The accuracy of the "spot" and "blush" signs as predictors of hematoma expansion and mortality was determined using receiver-operator characteristic (ROC) analysis. RESULTS: A total of 54 patients were identified as hypertensive ICH during the study period. "spot" sign was observed in 11 (20.4%) of the study population. Contrast extravasation (blush-sign) was seen in 7 (14.8%) patients. The "blush" was an independent predictor of hematoma expansion (odds ratio [OR] 6.052; confidence interval [CI] 1.036-15.945 [P = .012]) and mortality (OR 3.305; CI 1.240-25.414 [P = .032]). With ROC analysis, the "blush" sign was found to have a better predictive value for significant hematoma expansion (area under the curve [AUC]: .795) than the spot sign (AUC: .432). CONCLUSION: The "blush" sign has better accuracy for predicting hematoma expansion in hypertensive ICH and could be used to risk stratify these patients for early therapeutic interventions.

Chondrocyte-based intraoperative processing strategies for the biological augmentation of a polyurethane meniscus replacement.

Purpose/aim of study: Menisectomies account for over 1.5 million surgical interventions in Europe annually, and there is a growing interest in regenerative strategies to improve outcomes in meniscal replacement. The overall objective of this study was to evaluate the role of intraoperatively applied fresh chondrocyte (FC) isolates compared to minced cartilage (MC) fragments, used without cell isolation, to improve bioactivity and tissue integration when combined with a polyurethane replacement. MATERIALS AND METHODS: First, to optimize the intraoperative cell isolation protocol, caprine articular cartilage biopsies were digested with 750 U/ml or 3000 U/ml collagenase type II (ratio of 10 ml per g of tissue) for 30 min, 1 h or 12 h with constant agitation and compared to culture-expanded chondrocytes in terms of matrix deposition when cultured on polyurethane scaffolds. Finally, FCs and MC-augmented polyurethane scaffolds were evaluated in a caprine meniscal explant model to assess the potential enhancements on tissue integration strength. RESULTS: Adequate numbers of FCs were harvested using a 30 min chondrocyte isolation protocol and were found to demonstrate improved matrix deposition compared to standard culture-expanded cells in vitro. Upon evaluation in a meniscus explant defect model, both FCs and MC showed improved matrix deposition at the tissue-scaffold interface and enhanced push-out strength, fourfold and 2.5-fold, respectively, compared with the acellular implant. CONCLUSIONS: Herein, we have demonstrated a novel approach that could be applied intraoperatively, using FCs or MC for improved tissue integration with a polyurethane meniscal replacement.

Rapid Chondrocyte Isolation for Tissue Engineering Applications: The Effect of Enzyme Concentration and Temporal Exposure on the Matrix Forming Capacity of Nasal Derived Chondrocytes.

Laboratory based processing and expansion to yield adequate cell numbers had been the standard in Autologous Disc Chondrocyte Transplantation (ADCT), Allogeneic Juvenile Chondrocyte Implantation (NuQu®), and Matrix-Induced Autologous Chondrocyte Implantation (MACI). Optimizing cell isolation is a key challenge in terms of obtaining adequate cell numbers while maintaining a vibrant cell population capable of subsequent proliferation and matrix elaboration. However, typical cell yields from a cartilage digest are highly variable between donors and based on user competency. The overall objective of this study was to optimize chondrocyte isolation from cartilaginous nasal tissue through modulation of enzyme concentration exposure (750 and 3000 U/ml) and incubation time (1 and 12 h), combined with physical agitation cycles, and to assess subsequent cell viability and matrix forming capacity. Overall, increasing enzyme exposure time was found to be more detrimental than collagenase concentration for subsequent viability, proliferation, and matrix forming capacity (sGAG and collagen) of these cells resulting in nonuniform cartilaginous matrix deposition. Taken together, consolidating a 3000 U/ml collagenase digest of 1 h at a ratio of 10 ml/g of cartilage tissue with physical agitation cycles can improve efficiency of chondrocyte isolation, yielding robust, more uniform matrix formation.

Cell-based therapies for intervertebral disc and cartilage regeneration- Current concepts, parallels, and perspectives.

Lower back pain from degenerative disc disease represents a global health burden, and presents a prominent opportunity for regenerative therapeutics. While current regenerative therapies such as autologous disc chondrocyte transplantation (ADCT), allogeneic juvenile chondrocyte implantation (NuQu®), and immunoselected allogeneic adipose derived precursor cells (Mesoblast) show exciting clinical potential, limitations remain. The heterogeneity of preclinical approaches and the paucity of clinical guidance have limited translational outcomes in disc repair, lagging almost a decade behind cartilage repair. Advances in cartilage repair have evolved to single step approaches with improved orthopedic repair and regeneration. Elements from cartilage regeneration endeavors could be adopted and applied to harness translatable approaches and deliver a clinically and economically feasible regenerative surgery for back pain. In this article, we trace the developments behind the translational success of cartilage repair, examine elements to consider in achieving disc regeneration, and the need for surgical redesign. We further discuss clinical parameters, objectives, and coordination required to deliver improved regenerative surgery. Cell source, processing, and delivery modalities are key issues to be addressed in considering surgical redesign. Advances in biomanufacturing, tissue cryobanking, and point of care cell processing technology may enable intraoperative solutions for single step procedures. To maximize translational success a triad partnership between clinicians, industry, and researchers will be critical in providing instructive clinical guidelines for design as well as practical and economic considerations. This will allow a consensus in research ventures and add regenerative surgery into the algorithm in managing and treating a debilitating condition such as back pain. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:8-22, 2017.

Living Cell Factories - Electrosprayed Microcapsules and Microcarriers for Minimally Invasive Delivery.

Minimally invasive delivery of "living cell factories" consisting of cells and therapeutic agents has gained wide attention for next generation biomaterial device systems for multiple applications including musculoskeletal tissue regeneration, diabetes and cancer. Cellular-based microcapsules and microcarrier systems offer several attractive features for this particular purpose. One such technology capable of generating these types of systems is electrohydrodynamic (EHD) spraying. Depending on various parameters, including applied voltage, biomaterial properties (viscosity, conductivity) and needle geometry, complex structures and arrangements can be fabricated for therapeutic strategies. The advances in the use of EHD technology are outlined, specifically in the manipulation of bioactive and dynamic material systems to control size, composition and configuration in the development of minimally invasive micro-scaled biopolymeric systems. The exciting therapeutic applications of this technology, future perspectives and associated challenges are also presented.