Favorable long-term outcome in young adults undergoing surgery for lumbar disc herniation

Purpose The purpose of the study was to evaluate the long-term outcome after surgery for lumbar disc herniation in a young adult population. Methods A total of 526 consecutive patients between 18 and 40 years of age who underwent surgery for lumbar disc between 1990 and 2005 were included in the study. The primary outcomes were the need for new lumbar spine surgery during the follow-up and secondary outcomes were short-term subjective outcome, the Oswestry Disability Index (ODI) score, and the ability to carry out employment at the end of the long-term follow-up. Results A total of 96% of the patients had a reduction in their symptoms at the clinical follow-up (median of 50 days postsurgery). Twenty-one patients (4.0%) had a reoperation within 28 days. Excluding these early reoperations, 136 patients (26%) had additional lumbar spine surgery and 18 patients (3.4%) underwent lumbar fusion during the follow-up of median 18 years. The annual risk for new surgery was 1.4%. In total, 316 patients (60%) returned the ODI questionnaire, and their mean score was 8.1. Patients with a higher number of additional lumbar spine surgeries (p < 0.001) reported deteriorating ODI scores. Conclusion Patients showed excellent short-term recovery from their symptoms. In the long term, the mean ODI score for the patients was comparable to the normative population. However, a notable proportion of the patients required additional lumbar surgery during the follow-up period, and a higher number of lumbar surgeries was associated with poor ODI scores.Peer reviewe

Aikuisen autismikirjon häiriö

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Anterior cervical discectomy and fusion in young adults leads to favorable outcome in long-term follow-up

Background Context Anterior cervical discectomy and fusion (ACDF) procedures is thought to lead to accelerated degeneration of the adjacent cervical discs and in some cases can be symptomatic (adjacent segment disease, or ASD). The occurrence of ASD is of particular interest when treating young individuals, as the cumulative disease burden may become increasingly significant during their expectedly long lifetime. However, the overall impact of a surgical intervention on the lifetime prognosis of ASD remains unclear. Purpose Our goal was to study the long-term outcomes of ACDF surgery among those members of the young adult population who have been operated on between the ages of 18 and 40. Study design Retrospective study. Patient Sample All patients between 18 and 40 years of age at the time of surgery who underwent ACDF due to degenerative cervical disorders at Helsinki University Hospital between the years of 1990 and 2005 (476 patients). Outcome Measures Cervical reoperation rate, satisfaction with the surgery, employment status, Neck Disability Index (NDI) Methods We retrospectively analyzed the medical records of all patients between 18 and 40 years of age at the time of surgery who underwent ACDF due to degenerative cervical disorders at Helsinki University Hospital between the years of 1990 and 2005. We sent questionnaires to all available patients at the end of the follow-up (median 17.5 years) to assess their current neck symptoms, general situations, and levels of satisfaction with the surgery. Furthermore, we compared the results for different types of ACDF surgeries (i.e., discectomy only versus synthetic cage or bone autograft implantation for fusion) in propensity-score-matched groups. Results Of the 476 patients who were included in the study, surgery was performed in 72% of the cases due to intervertebral disc herniation and in 28% due to spondylotic changes. The total reoperation rate during the entire follow-up (median 17.5 years) was 24%, and 19.5% if early reoperations (Peer reviewe

Young adults undergoing ACDF surgery exhibit decreased health-related quality of life in the long term in comparison to the general population

BACKGROUND CONTEXT: The leading surgical treatment of cervical radiculopathy is anterior cervical discectomy and fusion (ACDF). However, it has been suggested that ACDF procedures could lead to accelerated degeneration of the adjacent cervical discs (adjacent segment disease, or ASD) and the effect of ACDF surgery on neck symptoms and quality of life in the long term is not fully understood. Patients operated on at young ages generally have a long life expectancy and a long number of working years ahead of them. Thus, this patient group is of special interest when considering the accumulation of cervical problems due to possible ASD, the overall progressive nature of cervical degeneration in the long term, and their effects on related quality of life. PURPOSE: Our goal was to study the health-related quality of life in the long-term follow-up after ACDF surgery in the young adult population between the ages of 18 and 40. STUDY DESIGN: A retrospective cohort study with propensity matched controls. PATIENT SAMPLE: All patients between 18 and 40 years of age at the time of the surgery who underwent ACDF due to degenerative cervical disease at Helsinki University Hospital between the years 1990 and 2005 who had filled in the quality of life questionnaires 12 to 28 years after the surgery (281 patients), and a propensity matched control cohort of the general population selected based on age, sex, and smoking status. OUTCOME MEASURES: Quality of life measured by the EuroQol questionnaire (EQ-5D-3L and EQ-VAS). METHODS: The medical records of all patients who underwent ACDF due to degenerative cervical disease at the age of 18 to 40 years at Helsinki University Hospital between 1990 and 2005 were analyzed retrospectively. The EuroQol questionnaire was sent to all patients whose contact information could be obtained (443 patients) at the end of the follow-up (median 17.5 years) to assess their current quality of life. A total of 281 patients returned the questionnaires and were included in this study. Quality of life was compared to that in the general Finnish population using a similar sized control cohort selected through propensity matching. RESULTS: The patients who had undergone ACDF surgery reported significantly more problems than the general population cohort in three out of five dimensions that were assessed in the EQ-5D questionnaire, including mobility, usual activities, and pain/discomfort. Similarly, the overall EQ-5D-3L index calculated from the dimensional values was lower (0.74 vs. 0.83, p=.000), depicting a generally decreased health-related quality of life among patients. Spondylosis as a primary diagnosis, clinical myelopathy, and further cervical surgeries were associated with lower quality of life in the subgroup analyses of the patients. Similarly, in the EQ-VAS assessment, patient subgroups with spondylosis as a primary diagnosis, at least one reoperation, operation on more than one level, and clinical myelopathy were associated with lower scores and lower quality of life. The mean EQ-VAS score among patients was 73%. Regardless of the decreased health-related quality of life, there was no statistically significant difference in the concurrent employment status between the patient and control groups. CONCLUSIONS: The health-related life quality measured by the EQ-5D-3L was lower in the patient population than in the general population. Patients had more problems with mobility and usual activities and more pain/discomfort. However, satisfaction with the surgery was very high, and there was no significant difference in employment status between the patients and the control population. Patients with spondylosis as a primary diagnosis had lower quality of life compared to patients with disc herniation. Also, clinical myelopathy and further cervical surgeries during follow-up were associated with lower quality of life in the subgroup analyses of the patients. It must also be kept in mind that we do not know what the situation could have been without surgery and with conservative treatment only. (C) 2021 The Authors. Published by Elsevier Inc.Peer reviewe

Oncograms Visualize Factors Influencing Long-Term Survival of Cancer Patients Treated with Adenoviral Oncolytic Immunotherapy

The first US Food and Drug Administration (FDA)- and EMA-approved oncolytic virus has been available since 2015. However, there are no markers available that would predict benefit for the individual patient. During 2007-2012, we treated 290 patients with advanced chemotherapy-refractory cancers, using 10 different oncolytic adenoviruses. Treatments were given in a Finnish Medicines Agency (FIMEA)-regulated individualized patient treatment program (the Advanced Therapy Access Program [ATAP]), which required long-term follow-up of patients, which is presented here. Focusing on the longest surviving patients, some key clinical and biological features are presented as "oncograms." Some key attributes that could be captured in the oncogram are suggested to predict treatment response and survival after oncolytic adenovirus treatment. The oncogram includes immunological laboratory parameters assessed in peripheral blood (leukocytes, neutrophil-to-lymphocyte ratio, interleukin-8 [IL-81, HMGB1, antiviral neutralizing antibody status), features of the patient (gender, performance status), tumor features (histological tumor type, tumor load, region of metastases), and oncolytic virus-specific features (arming of the virus). The retrospective approach used here facilitates verification in a prospective controlled trial setting. To our knowledge, the oncogram is the first holistic attempt to identify the patients most likely to benefit from adenoviral oncolytic virotherapy.Peer reviewe

Case-Control Estimation of the Impact of Oncolytic Adenovirus on the Survival of Patients With Refractory Solid Tumors

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Biodistribution Analysis of Oncolytic Adenoviruses in Patient Autopsy Samples Reveals Vascular Transduction of Noninjected Tumors and Tissues

In clinical trials with oncolytic adenoviruses, there has been no mortality associated with treatment vectors. Likewise, in the Advanced Therapy Access Program (ATAP), where 290 patients were treated with 10 different viruses, no vector-related mortality was observed. However, as the patient population who received adenovirus treatments in ATAP represented heavily pretreated patients, often with very advanced disease, some patients died relatively soon after receiving their virus treatment mandating autopsy to investigate cause of death. Eleven such autopsies were performed and confirmed disease progression as the cause of death in each case. The regulatory requirement for investigating the safety of advanced therapy medical products presented a unique opportunity to study tissue samples collected as a routine part of the autopsies. Oncolytic adenoviral DNA was recovered in a wide range of tissues, including injected and noninjected tumors and various normal tissues, demonstrating the ability of the vector to disseminate through the vascular route. Furthermore, we recovered and cultured viable virus from samples of noninjected brain metastases of an intravenously treated patient, confirming that oncolytic adenovirus can reach tumors through the intravascular route. Data presented here give mechanistic insight into mode of action and biodistribution of oncolytic adenoviruses in cancer patients.Peer reviewe

ADHD desynchronizes brain activity during watching a distracted multi-talker conversation

Individuals with attention-deficit/hyperactivity disorder (ADHD) have difficulties navigating dynamic everyday situations that contain multiple sensory inputs that need to either be attended to or ignored. As conventional experimental tasks lack this type of everyday complexity, we administered a film-based multi-talker condition with auditory distractors in the background. ADHD-related aberrant brain responses to this naturalistic stimulus were identified using intersubject correlations (ISCs) in functional magnetic resonance imaging (fMRI) data collected from 51 adults with ADHD and 29 healthy controls. A novel permutation-based approach introducing studentized statistics and subject-wise voxel-level null-distributions revealed that several areas in cerebral attention networks and sensory cortices were desynchronized in participants with ADHD (n = 20) relative to healthy controls (n = 20). Specifically, desynchronization of the posterior parietal cortex occurred when irrelevant speech or music was presented in the background, but not when irrelevant white noise was presented, or when there were no distractors. We also show regionally distinct ISC signatures for inattention and impulsivity. Finally, post-scan recall of the film contents was associated with stronger ISCs in the default-mode network for the ADHD and in the dorsal attention network for healthy controls. The present study shows that ISCs can further our understanding of how a complex environment influences brain states in ADHD.Peer reviewe

Mutation of the Fiber Shaft Heparan Sulphate Binding Site of a 5/3 Chimeric Adenovirus Reduces Liver Tropism

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Interleukin 8 activity influences the efficacy of adenoviral oncolytic immunotherapy in cancer patients

After the landmark approval of T-VEC, oncolytic viruses are finding their way to the clinics. However, response rates have still room for improvement, and unfortunately there are currently no available markers to predict responses for oncolytic immunotherapy. Interleukin 8 (IL-8) production is upregulated in many cancers and it also connects to several pathways that have been shown to impair the efficacy of adenoviral immunotherapy. We studied the role of IL-8 in 103 cancer patients treated with oncolytic adenoviruses. We found high baseline serum IL-8 concentration to be independently associated with poor prognosis (p <0.001). Further, normal baseline IL-8 was associated with improved prognostic potential of calculation of the neutrophil-to-lymphocyte ratio (p <0.001). Interestingly, a decrease in IL-8 concentration after treatment with oncolytic adenovirus predicted better overall survival (p <0.001) and higher response rate, although this difference was not significant (p=0.066). We studied the combination of adenovirus and IL-8 neutralizing antibody ex vivo in single cell suspensions and in co-cultures of tumor-associated CD15+ neutrophils and CD3+ tumor-infiltrating lymphocytes derived from fresh patient tumor samples. These results indicate a role for IL-8 as a biomarker in oncolytic virotherapy, but additionally provide a rationale for targeting IL-8 to improve treatment efficacy. In conclusion, curtailing the activity of IL-8 systemically or locally in the tumor microenvironment could improve anti-tumor immune responses resulting in enhanced efficacy of adenoviral immunotherapy of cancer. © Taipale et al.Peer reviewe