Peri-operative SARS-CoV-2 infection increases postoperative mortality. The aim of this study was to determine the optimal duration of planned delay before surgery in patients who have had SARS-CoV-2 infection. This international, multicentre, prospective cohort study included patients undergoing elective or emergency surgery during October 2020. Surgical patients with pre-operative SARS-CoV-2 infection were compared with those without previous SARS-CoV-2 infection. The primary outcome measure was 30-day postoperative mortality. Logistic regression models were used to calculate adjusted 30-day mortality rates stratified by time from diagnosis of SARS-CoV-2 infection to surgery. Among 140,231 patients (116 countries), 3127 patients (2.2%) had a pre-operative SARS-CoV-2 diagnosis. Adjusted 30-day mortality in patients without SARS-CoV-2 infection was 1.5% (95%CI 1.4-1.5). In patients with a pre-operative SARS-CoV-2 diagnosis, mortality was increased in patients having surgery within 0-2 weeks, 3-4 weeks and 5-6 weeks of the diagnosis (odds ratio (95%CI) 4.1 (3.3-4.8), 3.9 (2.6-5.1) and 3.6 (2.0-5.2), respectively). Surgery performed ≥ 7 weeks after SARS-CoV-2 diagnosis was associated with a similar mortality risk to baseline (odds ratio (95%CI) 1.5 (0.9-2.1)). After a ≥ 7 week delay in undertaking surgery following SARS-CoV-2 infection, patients with ongoing symptoms had a higher mortality than patients whose symptoms had resolved or who had been asymptomatic (6.0% (95%CI 3.2-8.7) vs. 2.4% (95%CI 1.4-3.4) vs. 1.3% (95%CI 0.6-2.0), respectively). Where possible, surgery should be delayed for at least 7 weeks following SARS-CoV-2 infection. Patients with ongoing symptoms ≥ 7 weeks from diagnosis may benefit from further delay.

Object. Posterolateral fusion involving instrumentation-assisted segmental fixation represents a valid procedure in the treatment of lumbar instability. In cases of anterior column failure, such as in isthmic spondylolisthesis, supplemental posterior lumbar interbody fusion (PLIF) may improve the fusion rate and endurance of the construct. Posterior lumbar interbody fusion is, however, a more demanding procedure and increases costs and risks of the intervention. The advantages of this technique must, therefore, be weighed against those of a simple posterior lumbar fusion. Methods. Thirty-five consecutive patients underwent pedicle screw fixation for isthmic spondylolisthesis. In 18 patients posterior lumbar fusion was performed, and in 17 patients PLIF was added. Clinical, economic, functional, and radiographic data were assessed to determine differences in clinical and functional results and biomechanical properties. At 2-year follow-up examination, the correction of subluxation, disc height, and foraminal area were maintained in the group in which a PLIF procedure was performed, but not in the posterolateral fusion—only group (p < 0.05). Nevertheless, no statistical intergroup differences were demonstrated in terms of neurological improvement (p = 1), economic (p = 0.43), or functional (p = 0.95) outcome, nor in terms of fusion rate (p = 0.49). Conclusions. The authors' findings support the view that an interbody fusion confers superior mechanical strength to the spinal construct; when posterolateral fusion is the sole intervention, progressive loss of the extreme correction can be expected. Such mechanical insufficiency, however, did not influence clinical outcome.

Object. The nuclear factor—κB (NF-κB) is a transcription factor that plays a pivotal role in the induction of genes involved in physiological processes and in the response to inflammation. The authors of recent studies have demonstrated that NF-κB and oxidative stress contribute to secondary injury after impact-induced spinal cord injury (SCI) in the rat. Dithiocarbamates are antioxidants that are potent inhibitors of NF-κB. The authors postulated that pyrrolidine dithiocarbamate (PDTC) would attenuate NF-κB—related inflammatory and oxidative events that occur after SCI. Methods. Spinal cord injury was induced by the application of vascular clips (force of 50 g) to the dura mater after a four-level T5–8 laminectomy. The authors investigated the effects of PDTC (30 mg/kg administered 30 minutes before SCI and 6 hours after SCI) on the development of the inflammatory response associated with SCI in rats. Levels of myeloperoxidase activity were measured as an indicator of polymorphonuclear infiltration; malondialdehyde levels in the spinal cord tissue were determined as an indicator of lipid peroxidation. The following studies were performed: immunohistochemical analysis to assess levels of inducible nitric oxide synthase (iNOS), nitrotyrosine formation, poly([adenosine diphosphate]-ribose) polymerase (PARP) activity; Western blot analysis to determine cytoplasmic levels of inhibitory—κB-α (IκB-α); and electrophoretic mobility-shift assay to measure the level of DNA/NF-κB binding. The PDTC treatment exerted potent antiinflammatory effects with significant reduction of polymorphonuclear cell infiltration, lipid peroxidation, and iNOS activity. Furthermore, administration of PDTC reduced immunohistochemical evidence of formation of nitrotyrosine and PARP activation in the spinal cord section obtained in the SCI-treated rats. Additionally, PDTC treatment significantly prevented the activation of NF-κB (electrophoretic mobility-shift assay and immunoblot analysis). Conclusions. Overall, the results clearly demonstrate that PDTC-related prevention of the activation of NF-κB reduces the development of some secondary injury events after SCI. Therefore, inhibition of NF-κB may represent a novel approach in the treatment of SCIs.

Spine metastases affect more than 70% of terminal cancer patients that eventually suffer from severe pain and neurological symptoms. Nevertheless, in the overwhelming majority of the cases, a spinal metastasis represents just one location of a diffuse systemic disease. Therefore, the best practice for treatment of spinal metastases depends on many different aspects of an oncological disease, including the assessment of neurological status, pain, location, and dissemination of the disease as well as the ability to predict the risk of disease progression with neurological worsening, benefits and risks associated to treatment and, eventually, expected survival. To address this need for a framework and algorithm that takes all aspects of care into consideration, we reviewed available evidence on the multidisciplinary management of spinal metastases. According to the latest evidence, the use of stereotactic radiosurgery (SRS) or stereotactic body radiotherapy (SBRT) for spinal metastatic disease is rapidly increasing. Indeed, aggressive surgical resection may provide the best results in terms of local control, but carries a significant rate of post-surgical morbidity whose incidence and severity appears to be correlated to the extent of resection. The multidisciplinary management represents, according to current evidence, the best option for the treatment of spinal metastases. Noteworthy, according to the recent literature evidence, cases that once required radical surgical resection followed by low-dose conventional radiotherapy, can now be more effectively treated by minimally invasive spinal surgery (MISS) followed by spine SRS with decreased morbidity, improved local control, and more durable pain control. This combination allows also extending this standard of care to patients that would be too sick for an aggressive surgical treatment.

SARS-CoV-2 has been associated with an increased rate of venous thromboembolism in critically ill patients. Since surgical patients are already at higher risk of venous thromboembolism than general populations, this study aimed to determine if patients with peri-operative or prior SARS-CoV-2 were at further increased risk of venous thromboembolism. We conducted a planned sub-study and analysis from an international, multicentre, prospective cohort study of elective and emergency patients undergoing surgery during October 2020. Patients from all surgical specialties were included. The primary outcome measure was venous thromboembolism (pulmonary embolism or deep vein thrombosis) within 30 days of surgery. SARS-CoV-2 diagnosis was defined as peri-operative (7 days before to 30 days after surgery); recent (1-6 weeks before surgery); previous (≥7 weeks before surgery); or none. Information on prophylaxis regimens or pre-operative anti-coagulation for baseline comorbidities was not available. Postoperative venous thromboembolism rate was 0.5% (666/123,591) in patients without SARS-CoV-2; 2.2% (50/2317) in patients with peri-operative SARS-CoV-2; 1.6% (15/953) in patients with recent SARS-CoV-2; and 1.0% (11/1148) in patients with previous SARS-CoV-2. After adjustment for confounding factors, patients with peri-operative (adjusted odds ratio 1.5 (95%CI 1.1-2.0)) and recent SARS-CoV-2 (1.9 (95%CI 1.2-3.3)) remained at higher risk of venous thromboembolism, with a borderline finding in previous SARS-CoV-2 (1.7 (95%CI 0.9-3.0)). Overall, venous thromboembolism was independently associated with 30-day mortality ). In patients with SARS-CoV-2, mortality without venous thromboembolism was 7.4% (319/4342) and with venous thromboembolism was 40.8% (31/76). Patients undergoing surgery with peri-operative or recent SARS-CoV-2 appear to be at increased risk of postoperative venous thromboembolism compared with patients with no history of SARS-CoV-2 infection. Optimal venous thromboembolism prophylaxis and treatment are unknown in this cohort of patients, and these data should be interpreted accordingly.

Symptomatic post-treatment edema (PTE) causing seizures, focal deficits, and intracranial hypertension is a rather common complication of meningioma radiosurgery. Factors associated to the occurrence of PTE still needs to be clarified. We retrospectively analyzed our patients’ data to identify factors associated with the development of symptomatic PTE. Supposed risk factors were systematically analyzed.Between July 2007 and March 2014, 245 meningiomas in 229 patients were treated by a single fraction or multisession radiosurgery (2-5 fractions) or hypofractionated stereotactic radiotherapy (6-15 fractions) using the CyberKnife system (Accuray Inc., Sunnyvale, CA) at the University Hospital of Messina, Italy.Local tumor control was achieved in 200 of 212 patients with World Health Organization (WHO) Grade I meningiomas (94%) at a mean follow-up of 62 months. Symptomatic PTE on MRI was diagnosed in 19 patients (8.3%) causing seizure (n=17, 89%), aggravating headache (n=12, 63%), or focal deficits (n=13, 68%). Four variables were found to be associated with the likelihood of edema development, including tumor volume > 4.5 mL, non-basal tumor location, tight brain/tumor interface, and atypical histology. Nonetheless, when multivariate logistic regression analysis was performed, only tumor volume and brain-tumor interface turned out to be independent predictors of PTE development.Our results suggest that the factor associated with the risk of developing PTE is associated to characteristics of meningioma rather than to the treatment modality used. Accordingly, an appropriate patient selection is the way to achieve safe treatment and long-term disease control.

IntroductionImage-guided robotic radiosurgery is an emerging minimally-invasive treatment option for trigeminal neuralgia (TN). Our group has treated 560 cases up to date, and report here the clinical outcomes of 387 treatments with three years follow-up. This study represents the largest single-center experience on CyberKnife radiosurgery for the treatment of TN so far reported.MethodsCyberKnife radiosurgery treatment was offered to patients with drug-resistant TN, after the failure of other treatments or refusal of invasive procedures. A second treatment was offered to patients with a poor response after the first treatment or with recurrent pain. Treatment protocol required the non-isocentric delivery of 60 Gy prescribed to the 80% isodose to a 6 mm retrogasserian segment of the affected trigeminal nerve. Retreatments typically received 45 Gy, again prescribed to the 80% isodose. The final plan was developed accordingly to individual anatomy and dose distribution over the trigeminal nerve, gasserian ganglion, and brainstem. Clinical outcomes such as pain control and hypoesthesia/numbness have been evaluated after 6, 12, 24, and 36 months. ResultsOur group has treated 527 patients with Cyberknife radiosurgery at Centro Diagnostico Italiano (CDI), Milan, Italy, during the last decade. A minimum follow-up of six months was available on 496 patients. These patients received 560 treatments: 435 patients (87.7%) had a single treatment, 60 patients (12.1%) had two treatments, and one patient (0.2%) had five treatments (two on the right side, three on the left side). Twenty four patients had multiple sclerosis (4.8%). Four hundred and forty-three patients (84%) received the treatment without previous procedures, while 84 patients (16%) underwent radiosurgery after the failure of other treatments. A neurovascular conflict was identified in 59% of the patients. Three hundred and forty-three patients (receiving a total of 387 treatments) had a minimum of 36 months follow up. Pain relief rate at 6, 12, 18, 24, 30 and 36 months was respectively 92, 87, 87, 82, 78 and 76%. Forty-four patients out of 343 (12.8%) required a second treatment during the observed period. At 36 months post-treatment, 21 patients (6,1%) reported the presence of bothering facial hypoesthesia. Eighteen patients out of 21 (85.7%) developed this complication after a repeated treatment. ConclusionsFrameless image-guided robotic radiosurgery in experienced hands is a safe and effective procedure for the treatment of TN, providing excellent pain control rates in the absence of major neurological complications. Repeated treatments due to recurrent pain are associated with restored pain control but at the price of a higher rate of sensory complications.

BACKGROUNDFrameless, non-isocentric irradiation of an extended segment of the trigeminal nerve introduces new concepts in stereotactic radiosurgery for medically resistant trigeminal neuralgia (TN).OBJECTIVETo report the results of the largest single-center experience about image-guided robotic radiosurgery for TN.METHODSA cohort of 138 patients treated with CyberKnife® (Accuray Incorporated, Sunnyvale, California) radiosurgery with a minimum follow-up of 36 mo were recruited. Pain relief, medications, sensory disturbances, rate and time of pain recurrence were prospectively analyzed.RESULTSMedian follow-up was 52.4 mo; median dose 75 Gy; median target length 5.7-mm; median target volume 40 mm³; median prescription dose 60 Gy (80% isodose line). Actuarial pain control rate (Barrow Neurological Institute [BNI] class I-IIIa) at 6, 12, 24, and 36 mo were 93.5%, 85.8%, 79.7%, and 76%, respectively. Overall, 33 patients (24%) required a second treatment.Overall, 18.1% developed sensory disturbances after 16.4 ± 8.7 mo. One patient (0.7%) developed BNI grade IV dysfunction; 6 (4.3%) developed BNI grade III (somewhat bothersome) hypoesthesia after retreatment; BNI grade II (not bothersome) hypoesthesia was reported by 18 patients (11 after retreatment). Shorter nerve length (<6 mm vs 6 mm), smaller nerve volume (<30 mm3 vs >30 mm3), and lower prescription dose (<58 vs >58 Gy) were associated with treatment failure (P = .01, P = .02, P = .03, respectively). Re-irradiation independently predicted sensory disturbance (P < .001).CONCLUSIONTargeting a 6-mm segment of the trigeminal nerve with a prescribed dose of 60 Gy appears safe and effective. Persistent pain control was achieved in most patients with acceptable risk of sensory complications, which were typically found after re-irradiation.