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Study Design: Retrospective cohort study.

Objective: Spinal metastases are common in patients with breast cancer, and accurate estimation of postoperative survival is crucial for selecting appropriate candidates for metastasis surgery. This study investigated the association between breast cancer subtype, according to the St. Gallen classification, and survival after surgery for spinal metastases with the aim of improving prognostic assessment and supporting informed patient counselling.

Methods:: This study included 110 patients with breast cancer who underwent surgery for spinal metastases identified from the Swedish Spine Register and the Swedish National Quality Register of Breast Cancer. Patients were categorized in terms of the breast cancer subtype according to the St. Gallen classification. Postoperative survival was analysed using Kaplan-Meier estimates and a Cox proportional hazards model.

Results: The overall median survival following spinal surgery was 25 months (95% CI 19-31), while the median postoperative survival by subtype was 39 months (95% CI 28-50) for luminal A patients, 20 months (95% CI 9-31) for luminal B patients, and 48 months (95% CI 20-76) for luminal B/HER2+ patients. The median survival was not reached for the nonluminal HER2+ group, whereas patients with triple-negative breast cancer had a median survival of only 5 months (95% CI 4-6). The St. Gallen subtype was significantly associated with postoperative survival according to univariable (P<0.001) and multivariable analyses (P = 0.011).

Conclusions: Breast cancer subtype according to the St. Gallen classification was significantly associated with survival after surgery for spinal metastases. These findings indicate that the St. Gallen classification may serve as a valuable prognostic tool in the metastatic spine setting. Incorporation of molecular subtype information may improve estimation of postoperative survival and support informed patient counselling, expectation management, and individualized surgical decision-making in patients with breast cancer spinal metastases.

INTRODUCTION: Pain, comprising sensory and emotional elements, is influenced by pain catastrophizing, which magnifies pain and promotes helplessness and rumination. This study explores the relationship between pain catastrophizing and outcomes following selective nerve root blockade (SNRB) in patients with lumbar radicular pain (LRP).

METHODS: A prospective cohort study of 103 LRP patients, confirmed by MRI, was conducted. All participants underwent SNRB at Umeå University Hospital. Outcomes were measured using PROMIS-29 and the Pain Catastrophizing Scale (PCS) at baseline and several intervals up to 84 days post-intervention. Patients were categorized into responder (≥30% pain reduction) and non-responder groups and stratified into three groups based on baseline PCS scores. Changes in outcomes from baseline to 14 days post-SNRB were analyzed in relation to PCS groups. PCS changes over time were evaluated between responders and non-responders. Statistical analyses assessed PCS and outcome changes.

RESULTS: Baseline pain catastrophizing was not a significant predictor of pain response to SNRB. However, responders demonstrated significant reductions in pain catastrophizing following the intervention, suggesting that SNRB may influence cognitive coping mechanisms related to pain.

CONCLUSION: SNRB reduces pain catastrophizing in LRP patients, although baseline catastrophizing does not predict pain outcomes. Addressing catastrophizing remains important but may serve better as an outcome measure rather than a predictor of treatment response.

Introduction: The increasing adoption of digital health care solutions offers a transformative opportunity to improve patient access while addressing sustainability and cost-efficiency challenges. Our study evaluates a virtual remote care system (VRCS) that has been implemented at our clinic in northern Sweden. By combining patient-centered outcomes, environmental metrics, and health economic models, this study examines the impact of a VRCS on patient satisfaction, resource utilization, and environmental sustainability.

Materials and Methods: Eighty patients with chronic pain, treated with spinal cord or dorsal root ganglion stimulation, participated in this study. All accessed the NeuroSphere Virtual Clinic platform for remote consultations and troubleshooting. A patient satisfaction survey assessed usability, trust, and preference for digital vs in-person consultations. A health economic model analyzed travel costs, CO₂ emissions, and time burdens for in-clinic consultations vs a mixed care pathway across three scenarios of VRCS adoption (20%, 50%, and 100%).

Results: The survey results indicated high levels of patient satisfaction, with an average score of 9.1 out of 10, and strong trust in the platform, reported by 98.75% of participants. The introduction of digital consultations led to substantial reductions in travel-related burdens, including a 75% decrease in costs, CO₂ emissions, and travel time during the first year, stabilizing at a 70% reduction in subsequent years. Patients traveling over 500 km experienced the greatest benefits, with annual savings of €525, a reduction of 231 kg in CO₂ emissions, and 19 fewer hours of travel time. The mixed care pathways enhanced accessibility, reducing cancellations and no-shows by up to 59%. Despite increased troubleshooting consultations, hospital resource utilization remained stable, with only marginal increases in workload and space utilization.

Discussion: The VRCS aligns with key health care priorities, including improving access, enhancing patient experience, and promoting sustainability. It addresses regional challenges, such as long travel distances and harsh winters, while reducing the ecological footprint of health care delivery. The platform's ability to decrease travel burdens and CO₂ emissions aligns with global sustainability goals. However, barriers such as digital literacy and data privacy require further attention to ensure equitable access.

Conclusions: The VRCS demonstrates significant benefits, including high patient satisfaction, reduced travel burdens, and improved resource utilization. By aligning with sustainability objectives, it offers a scalable model for digital transformation in health care, underscoring the importance of continued investment in remote care technologies.

Objectives: Chronic low back pain (CLBP) is one of the most common chronic pain conditions that cause both individual suffering and a burden to society. For these patients, several interventional treatment options such as surgery, blocks, radiofrequency, and spinal cord stimulation are available. Lately, dorsal root ganglion stimulation (DRG-S) also has been mentioned as an option by targeting bilateral T12 dorsal ganglia. In this study, we present the outcome of 11 patients with CLBP treated with bilateral T12 DRG-S.

Materials and Methods: Thirteen patients with CLBP with and without leg pain were treated with bilateral T12 DRG-S. Three of the patients also received a third lumbar lead owing to leg pain. Eleven of the patients had >50% pain relief during the peri- or/and postoperative testing and received a fully implantable neurostimulator. Pain intensity, general health status, quality of life, pain catastrophizing, mental status, sleeping disorder, physical activity, and patient satisfaction were followed using numeric rating scale (NRS), Patient-Reported Outcomes Measurement Information System 29 version 2.1, Pain Catastrophizing Score, Generalized Anxiety Disorder 7-item scale, Patient Health Questionnaire Depression Module, Insomnia Severity Index, and Patient Satisfaction Questionnaire at baseline before implantation and at three months and six months. The results were analyzed on the basis of six domains: pain relief, sleeping disorder, social ability, mental status, physical activity, and satisfaction. To be identified as a responder, the patients should show a significant improvement in the pain relief domain together with at least two other domains. All responders also were given the opportunity to test 4-Hz DRG-S and compare it with traditional 20-Hz stimulation.

Results: All 11 patients were identified as responders at six months. Five of the patients had >80% pain relief, with an average NRS score reduction of 71% for the whole group. Significant improvement could be observed in three domains for one patient, four domains for three patients, five domains for six patients, and six domains for one patient. Seven patients chose to try 4-Hz stimulation. All seven identified 4-Hz stimulation as at least as good as or better than 20-Hz stimulation and chose to continue with 4-Hz stimulation.

Conclusions: Bilateral T12 DRG-S seems to be an effective treatment for chronic low back pain, with significant beneficial effect not only on pain but also on quality of life, pain catastrophizing, mental status, sleeping disorder, and physical activity. 4-Hz DRG-S gave a result comparable with or better than 20-Hz stimulation.

Background: Dorsal root ganglion stimulation (DRG-S) has emerged as a novel therapeutic approach for managing chronic neuropathic pain.

Aims: This study aims to compare the effectiveness of 4–20 Hz DRG-S through a retrospective analysis of a cohort of 28 patients with various neuropathic pain etiologies and pain locations.

Materials and Methods: Patient responses to both stimulation frequencies were examined using the Numeric Rating Scale (NRS) and Patient Global Impression of Change (PGIC) assessments. Factors such as patient preference and satisfaction were also evaluated.

Results: The results indicate that 4 Hz DRG-S is not only as effective as 20 Hz stimulation but may also surpass it. Among the 28 patients, 26 assessed 4 Hz stimulation to be at least as effective as 20 Hz, with the majority (22 out of 26) considering 4 Hz stimulation superior. After trying 4 Hz stimulation, 24 out of 28 patients chose it over 20 Hz, while two patients opted for a combination of both settings. Only two patients reverted to their original 20 Hz stimulation program. A statistically significant pain reduction of 24% was observed when comparing the effects of 4 Hz versus 20 Hz.

Discussion: The study highlights the broader applicability of low-frequency DRG-S, extending its benefits beyond the realm of low back pain. Patients with diverse pain etiologies and locations experienced comparable positive outcomes, suggesting that the advantages of low-frequency stimulation are not confined to specific pain types or locations.

Conclusion: This study emphasizes the potential of 4 Hz DRG-S as a valuable alternative to the standard 20 Hz stimulation. Although the exact mechanisms require further investigation, the observed clinical benefits and patient preferences for low-frequency stimulation suggest its viability across diverse pain indications and locations. Additional research is necessary to substantiate these findings and assess the durability and economic implications of low-frequency DRG-S.

Purpose: Selective nerve root blocks (SNRB) are used both as a therapeutic and diagnostic tool for lumbar radicular pain. Most studies evaluate the effect of SNRB simply by its relation to pain reduction. It is well known that pain is associated with other factors such as depression, anxiety, inactivity and sleeping disorders, but these patient-related outcomes are seldom evaluated. This study evaluated the influence of SNRB on pain-related outcomes including depression, anxiety, fatigue, pain interference, activity and sleep.

Methods: One hundred three patients with lumbar radicular pain were treated with a SNRB. Patient-reported outcome measures (PROMs) were assessed with the PROMIS-29 for 12 weeks (84 days) following the SNRB. Patients were stratified based on their pain reduction at the 14-day follow up as responders (≥ 30% pain reduction) and non-responders (< 30% pain reduction). Post-treatment duration was estimated with the Kaplan–Meier analysis with return to baseline as an event. A paired t-test was used to compare pre- and post-treatment responses at specific time intervals.

Results: Forty-four percent (n = 45) of the patients were responders and showed significant improvement in all parameters throughout the 84-days follow-up, the exception was sleep that lost significance at day 70. The mean post-treatment duration among responders was 59 (52–67) days. Non-responders showed significant improvements in pain interference and pain intensity until day 35 and in ability for social participation until 21-day.

Conclusion: SNRB can improve pain intensity, pain interference, physical function, fatigue, anxiety, depression, sleep disturbance and the ability to participate in social roles.

Purpose: This study evaluates the application of a microdialysis technique for interstitial chemotherapy using cisplatin in high-grade glioma.

Method: An in vitro study demonstrated that cisplatin can be administered through retrograde microdialysis and defined the recovery for cisplatin. In a subsequent phase I study, 1–4 microdialysis catheters were implanted in tumor tissue, brain adjacent to tumor (BAT) tissue, and subcutaneous tissue in 10 patients with recurrent high-grade glioma. Cisplatin was administered continuously in daily doses between 0.3 and 3.9 mg for 4 to12 days. Microdialysis samples were continuously collected and analyzed for glucose metabolites, glutamate, glycerol, and cisplatin concentrations. Treatment tolerability was evaluated through clinical monitoring. Quality of life was assessed using the EORTC-QLQ-C30 questionnaire for up to 3 months after treatment.

Results: This in vitro study showed that cisplatin could be administrated with a recovery of 41–97%, depending on flowrate, type of catheter, and cisplatin concentration. During the treatment, patients were exposed to a total dose of 1.2–36.8 mg cisplatin. The concentration of cisplatin in BAT, serum, and subcutaneous tissue was close to detection level in all but two patients. A transient neurologic deterioration due to edema was commonly observed, but no systemic side effects were recorded. After onset of treatment, concentrations of glutamate and glycerol were significantly increased in tumor tissue but not in BAT, with a peak after 3 days, and consistent for the rest of the treatment. Five of the patients survived between 153 and 492 days after treatment.

Conclusion: This phase I study demonstrates that retrograde microdialysis can be used to administer cisplatin interstitially into high-grade glioma tissue. A high cytotoxicity was detected in tumor tissue, but not in the surrounding brain. Retrograde microdialysis appears to be a clinically useful method for intratumoral drug administration in high-grade glioma.

BACKGROUND: High-grade gliomas are associated with poor prognosis. Tumour heterogeneity and invasiveness create challenges for effective treatment and use of systemically administrated drugs. Furthermore, lack of functional predictive response-assays based on drug efficacy complicates evaluation of early treatment responses.

METHODS: We used microdialysis to deliver cisplatin into the tumour and to monitor levels of metabolic compounds present in the tumour and non-malignant brain tissue adjacent to tumour, before and during treatment. In parallel, we collected serum samples and used multivariate statistics to analyse the metabolic effects.

RESULTS: We found distinct metabolic patterns in the extracellular fluids from tumour compared to non-malignant brain tissue, including high concentrations of a wide range of amino acids, amino acid derivatives and reduced levels of monosaccharides and purine nucleosides. We found that locoregional cisplatin delivery had a strong metabolic effect at the tumour site, resulting in substantial release of glutamic acid, phosphate, and spermidine and a reduction of cysteine levels. In addition, patients with long-time survival displayed different treatment response patterns in both tumour and serum. Longer survival was associated with low tumour levels of lactic acid, glyceric acid, ketoses, creatinine and cysteine. Patients with longer survival displayed lower serum levels of ketohexoses, fatty acid methyl esters, glycerol-3-phosphate and alpha-tocopherol, while elevated phosphate levels were seen in both tumour and serum during treatment.

CONCLUSION: We highlight distinct metabolic patterns associated with high-grade tumour metabolism, and responses to cytotoxic cisplatin treatment.

Glioblastoma multiforme, the most common primary brain tumor, has a dire prognosis despite multimodal treatments that include surgery and radio-chemotherapy. To improve the outcome of this destructive disease, we need to improve our understanding of its tumor biology. Furthermore, the development of new treatment strategies will improve with a better understanding of the interplay between malignant cells and their direct surrounding microenvironment.

This thesis aims to increase the understanding of the processes within high-grade glioma and its microenvironment during normal conditions as well as during the distress associated with treatment. Specifically, we have investigated the metabolic response to radiotherapy (study I and II), the immunologic response to radiotherapy (study II), and the metabolic response pattern to loco-regional treatment with cisplatin (study III and IV). Using microdialysis, we collected samples from the extracellular space in both normal brain and tumor tissue during radiotherapy (study I and II) and loco-regional cisplatin treatment (study III and IV). Theses samples were analyzed for glucose metabolites, glycerol, and glutamate (study I, II, and III) and for cytokines (study II). In addition, we analyzed the global metabolism with mass spectrometry to identify and assess the response pattern of malignant glioma cells to loco-regional cisplatin treatment (study IV).

In study I and II, we found that malignant glioma cells used glucose at a higher rate than normal cells and preferred glycolysis for glucose metabolism. The given radiation dose (2 Gray (Gy) daily for five days) did not significantly affect glucose metabolism, glycerol levels, or glutamate levels in tumor tissue or the microenvironment. However, in study II, we observed an induced inflammatory effect due to the given radiation dose as several of the cytokines investigated showed significantly increased levels during radiotherapy. In study IV, we observed a complex and strong metabolic response to the loco-regional cisplatin therapy. At baseline, we found a metabolic pattern corresponding well with highly proliferating tumor tissue–i.e., high levels of amino acids, their metabolites, and other metabolic end products and low levels of sugar derivatives, antioxidants, and nucleotides. During the loco-regional therapy, we observed a clearly localized cytotoxic effect within the tumor and a metabolic response pattern corresponding with cisplatin’s complex mechanism of action, affecting several metabolic pathways within the malignant cell. Glutamate and glycerol also increased in tumor tissue following loco-regional treatment, a finding that further supported the observation of local toxicity.

In study III, we investigated microdialysis as a method to assess the microenvironment in high-grade glioma and as a method for drug delivery (retrograde microdialysis). All studies demonstrated the usefulness of microdialysis as a tool for in vivo real-time assessment of molecular events in malignant glioma tissue. Although the method is invasive, no complications related to the surgical procedure or assessment were noted. In study III, we also demonstrated that retrograde microdialysis is a feasible method for locally delivering clinically significant doses of drugs such as cisplatin to tumor tissue in the brain. However, in addition to having a cytotoxic effect on tumor cells, cisplatin may induce clinically significant edema.

Purpose: Management of patients with persisting pain after spine surgery (PPSS) shows significant variability, and there is limited evidence from clinical studies to support treatment choice in daily practice. This study aimed to develop patient-specific recommendations on the management of PPSS.

Methods: Using the RAND/UCLA appropriateness method (RUAM), an international panel of 6 neurosurgeons, 6 pain specialists, and 6 orthopaedic surgeons assessed the appropriateness of 4 treatment options (conservative, minimally invasive, neurostimulation, and re-operation) for 210 clinical scenarios. These scenarios were unique combinations of patient characteristics considered relevant to treatment choice. Appropriateness had to be expressed on a 9-point scale (1 = extremely inappropriate, 9 = extremely appropriate). A treatment was considered appropriate if the median score was ≥ 7 in the absence of disagreement (≥ 1/3 of ratings in each of the opposite sections 1–3 and 7–9).

Results: Appropriateness outcomes showed clear and specific patterns. In 48% of the scenarios, exclusively one of the 4 treatments was appropriate. Conservative treatment was usually considered appropriate for patients without clear anatomic abnormalities and for those with new pain differing from the original symptoms. Neurostimulation was considered appropriate in the case of (predominant) neuropathic leg pain in the absence of conditions that may require surgical intervention. Re-operation could be considered for patients with recurrent disc, spinal/foraminal stenosis, or spinal instability.

Conclusions: Using the RUAM, an international multidisciplinary panel established criteria for appropriate treatment choice in patients with PPSS. These may be helpful to educate physicians and to improve consistency and quality of care.