Search

Background Depression and anxiety are common mental disorders among patients with chronic pain. It is hypothesised that patients suffering from these disorders benefit less from cervical spine surgery than mentally healthy patients. Therefore, this study aimed to quantify the effect of mental health status on functional outcome after anterior cervical discectomy in a post hoc analysis on RCT data. Methods One hundred eight patients from the NECK trial, with radiculopathy due to a one-level herniated disc, underwent anterior cervical discectomy and were included into this analysis. Functional outcome was quantified using the Neck Disability Index (NDI), and mental health status was measured using the Hospital Anxiety and Depression Score (HADS) questionnaire. NDI differences were assessed using generalised estimated equations (GEE), crude means, a predictive linear mixed model (LMM) using baseline scores and over time with an explanatory LMM. Results At baseline, 24% and 32% of patients were respectively depressed and anxious and had statistically significant and clinically relevant higher NDI scores during follow-up. However, in those patients in which the HADS returned to normal during follow-up, NDI values decreased comparably to the non-depression or non-anxiety cases. Those patients that demonstrated persisting high HADS values had convincingly worse NDI scores. A predictive LMM showed that combining baseline NDI and HADS scores was highly predictive of NDI during follow-up. The R shiny application enabled the effective, visual communication of results from the predictive LMM. Conclusion This study shows that mental health status and disability are strongly associated and provides insight into the size of the effect, as well as a way to use this relation to improve preoperative patient counselling. These findings give rise to the suggestion that incorporating mental health screening in the preoperative assessment of patients could help to adequately manage patients’ expectations for functional recovery. Trial registration Dutch Trial Register Number: NTR1289

Motion preserving anterior cervical disc arthroplasty (ACDA) in patients with cervical radiculopathy was introduced to prevent symptomatic adjacent segment disease as compared to anterior cervical discectomy and fusion (ACDF).To evaluate the long-term outcome in patients with cervical radiculopathy due to a herniated disc undergoing ACDA, ACDF or ACD (no cage, no plate) in terms of clinical outcome measured by the Neck Disability Index (NDI). Likewise, clinically relevant adjacent segment disease is assessed as a long-term result.Double-blinded randomized controlled trial.A total of 109 patients with one level herniated disc were randomized to one of the following treatments: ACDA, ACDF with intervertebral cage, ACD without cage.Clinical outcome was measured by patients' self-reported NDI, Visual Analogue Scale (VAS) neck pain, VAS arm pain, SF36, EQ-5D, perceived recovery and reoperation rate. Radiological outcome was assessed by radiographic cervical curvature and adjacent segment degeneration (ASD) parameters at baseline and up until five years after surgery.To account for the correlation between repeated measurements of the same individual Generalized Estimated Equations (GEE) were used to calculate treatment effects, expressed in difference in marginal mean values for NDI per treatment group.Clinical outcome parameters were comparable in the ACDA and ACDF group, but significantly worse in the ACD group, though not reaching clinical relevance. Annual reoperation rate was 3.6% in the first two years after surgery, declined to 1.9% in the years thereafter. The number of reoperations for ASD was not lower in the ACDA group, while the number of reoperations at the index level was higher after ACD, when compared to ACDF and ACDA.A persisting absence of clinical superiority was demonstrated for the cervical disc prosthesis five years after surgery. Specifically, clinically relevant adjacent level disease was not prevented by implanting a prosthesis. Single level ACD without implanting an intervertebral device provided worse clinical outcome, which was hypothesized to be caused by delayed fusion. This stresses the need for focusing on timely fusion in future research.

BACKGROUND Surgical management of spine deformity is associated with significant morbidity. Recent literature has inconsistently demonstrated better outcomes after utilizing 2 attending surgeons for spine deformity. OBJECTIVE To conduct a systematic review and meta-analysis on studies reporting outcomes following single- vs dual-attending surgeons for spine deformity. METHODS MEDLINE, Embase, Web of science, and Cochrane databases were last searched on July 16, 2020. A total of 1013 records were identified excluding duplicates. After screening, 10 studies (4 cohort, 6 case series) were included in the meta-analysis. Random-effect models were used to pool the effect estimates by study design. When feasible, further subgroup analysis by deformity type was conducted. RESULTS A total of 953 patients were analyzed. Pooled results from propensity score-matched cohort studies revealed that the single-surgeon approach was unfavorably associated with a nonstatistically significant higher blood loss (mean difference = 421.0 mL; 95% CI: -28.2, 870.2), a statistically significant higher operative time (mean difference = 94.3 min; 95% CI: 54.9, 133), length of stay (mean difference = 0.84 d; 95% CI: 0.46, 1.22), and an increased risk of complications (Mantel-Haenszel risk ratio = 2.93; 95% CI: 1.12, 7.66). Data from pooled case series demonstrated similar results for all outcomes. Moreover, these results did not differ significantly between deformity types (adolescent idiopathic scoliosis and adult spinal deformity). CONCLUSION Dual-attending surgeon approach appeared to be associated with reduced operative time, shorter hospital stays, and reduced risk of complications. These findings may potentially improve outcomes in surgical treatment of spine deformity.

Background Lung cancer is still the main cause of cancer death worldwide despite the availability of targeted therapies and immune-checkpoint inhibitors combined with chemotherapy. Cancer cell heterogeneity and primary or acquired resistance mechanisms cause the elusive behaviour of this cancer and new biomarkers and active drugs are urgently needed to overcome these limitations. p65BTK, a novel isoform of the Bruton Tyrosine Kinase may represent a new actionable target in non-small cell lung cancer (NSCLC). Methods p65BTK expression was evaluated by immunohistochemistry in 382 NSCLC patients with complete clinico-pathological records including smoking habit, ALK and EGFR status, and in metastatic lymph nodes of 30 NSCLC patients. NSCLC cell lines mutated for p53 and/or a component of the RAS/MAPK pathway and primary lung cancer-derived cells from Kras/Trp53 null mice were used as a preclinical model. The effects of p65BTK inhibition by BTK Tyrosine Kinase Inhibitors (TKIs) (Ibrutinib, AVL-292, RN486) and first-generation EGFR-TKIs (Gefitinib, Erlotinib) on cell viability were evaluated by MTT. The effects of BTK-TKIs on cell growth and clonogenicity were assessed by crystal violet and colony assays, respectively. Cell toxicity assays were performed to study the effect of the combination of non-toxic concentrations of BTK-TKIs with EGFR-TKIs and standard-of-care (SOC) chemotherapy (Cisplatin, Gemcitabine, Pemetrexed). Results p65BTK was significantly over-expressed in EGFR-wild type (wt) adenocarcinomas (AdC) from non-smoker patients and its expression was also preserved at the metastatic site. p65BTK was also over-expressed in cell lines mutated for KRAS or for a component of the RAS/MAPK pathway and in tumors from Kras/Trp53 null mice. BTK-TKIs were more effective than EGFR-TKIs in decreasing cancer cell viability and significantly impaired cell proliferation and clonogenicity. Moreover, non-toxic doses of BTK-TKIs re-sensitized drug-resistant NSCLC cell lines to both target- and SOC therapy, independently from EGFR/KRAS status. Conclusions p65BTK results as an emerging actionable target in non-smoking EGFR-wt AdC, also at advanced stages of disease. Notably, these patients are not eligible for EGFR-TKIs-based therapy due to a lack of EGFR mutation. The combination of BTK-TKIs with EGFR-TKIs is cytotoxic for EGFR-wt/KRAS-mutant/p53-null tumors and BTK-TKIs re-sensitizes drug-resistant NSCLC to SOC chemotherapy. Therefore, our data suggest that adding BTK-TKIs to SOC chemotherapy and EGFR-targeted therapy may open new avenues for clinical trials in currently untreatable NSCLC. Electronic supplementary material The online version of this article (10.1186/s13046-019-1199-7) contains supplementary material, which is available to authorized users.

Background context - Defining clinically meaningful success criteria from patient-reported outcome measures (PROMs) is crucial for clinical audits, research and decision-making. Purpose - We aimed to define criteria for a successful outcome 3 and 12 months after surgery for cervical degenerative radiculopathy on recommended PROMs. Study design - Prospective cohort study with 12 months follow-up. Patient sample - Patients operated at one or two levels for cervical radiculopathy included in the Norwegian Registry for Spine Surgery (NORspine) from 2011 to 2016. Outcome measures - Neck disability index (NDI), Numeric Rating Scale for neck pain (NRS-NP) and arm pain (NRS-AP), health-related quality-of-life EuroQol 3L (EQ-5D), general health status (EQ-VAS). Methods - We included 2,868 consecutive cervical degenerative radiculopathy patients operated for cervical radiculopathy in one or two levels and included in the Norwegian Registry for Spine Surgery (NORspine). External criterion to determine accuracy and optimal cut-off values for success in the PROMs was the global perceived effect scale. Success was defined as “much better” or “completely recovered.” Cut-off values were assessed by analyzing the area under the receiver operating curves for follow-up scores, mean change scores, and percentage change scores. Results - All PROMs showed high accuracy in defining success and nonsuccess and only minor differences were found between 3- and 12-month scores. At 12 months, the area under the receiver operating curves for follow-up scores were 0.86 to 0.91, change scores were 0.74 to 0.87, and percentage change scores were 0.74 to 0.91. Percentage scores of NDI and NRS-AP showed the best accuracy. The optimal cut-off values for each PROM showed considerable overlap across those operated due to disc herniation and spondylotic foraminal stenosis. Conclusions - All PROMs, especially NDI and NRS-AP, showed good to excellent discriminative ability in distinguishing between a successful and nonsuccessful outcome after surgery due to cervical radiculopathy. Percentage change scores are recommended for use in research and clinical practice.

Purpose Cervical spine surgery may affect sagittal alignment parameters and induce accelerated degeneration of the cervical spine. Cervical sagittal alignment parameters of surgical patients will be correlated with radiological adjacent segment degeneration (ASD) and with clinical outcome parameters. Methods Patients were analysed from two randomized, double-blinded trials comparing anterior cervical discectomy with arthroplasty (ACDA), with intervertebral cage (ACDF) and without intervertebral cage (ACD). C2–C7 lordosis, T1 slope, C2–C7 sagittal vertical axis (SVA) and the occipito-cervical angle (OCI) were determined as cervical sagittal alignment parameters. Radiological ASD was scored by the combination of decrease in disc height and anterior osteophyte formation. Neck disability index (NDI), SF-36 PCS and MCS were evaluated as clinical outcomes. Results The cervical sagittal alignment parameters were comparable between the three treatment groups, both at baseline and at 2-year follow-up. Irrespective of surgical method, C2–C7 lordosis was found to increase from 11° to 13°, but the other parameters remained stable during follow-up. Only the OCI was demonstrated to be associated with the presence and positive progression of radiological ASD, both at baseline and at 2-year follow-up. NDI, SF-36 PCS and MCS were demonstrated not to be correlated with cervical sagittal alignment. Likewise, a correlation with the value or change of the OCI was absent. Conclusion OCI, an important factor to maintain horizontal gaze, was demonstrated to be associated with radiological ASD, suggesting that the occipito-cervical angle influences accelerated cervical degeneration. Since OCI did not change after surgery, degeneration of the cervical spine may be predicted by the value of OCI. NECK trial Dutch Trial Register Number NTR1289. PROCON trial Trial Register Number ISRCTN41681847. Graphic abstract These slides can be retrieved under Electronic Supplementary Material.

Study Design. Retrospective analysis was performed on data from 251 patients that were included in two randomized, double-blinded clinical trials comparing clinical results of anterior cervical discectomy and arthroplasty (ACDA) to anterior cervical discectomy and fusion (ACDF), and anterior cervical discectomy (ACD), for single-level disc herniation. Objective. This study aimed to investigate whether the ACDA procedure offers superior clinical results 2 years after surgery, to either ACDF or ACD without instrumentation, in the entire group of patients or in a particular subgroup of patients. Summary of Background Data. The cervical disc prosthesis was introduced to provide superior clinical outcomes after ACD. Methods. Neck Disability Index (NDI), and subscales of the 36-item short-form health survey (SF-36) and McGill pain score were collected at baseline, 1 year and 2 years after surgery. Reoperations and complications were also evaluated. A preliminary subgroup analysis was performed for age, disc height, body mass index (BMI), smoking, and sex. Results. The NDI decreased comparably in all treatment arms to circa 50% of the baseline value and marginal mean NDI differences varied from 0.4 to 1.1 on a 100 point NDI scale, with confidence intervals never exceeding the 20-point minimal clinical important difference (MCID). Secondary outcome parameters showed comparable results. Preliminary subgroup analysis could not demonstrate clinically relevant differences in NDI between treatments after 2 years. Conclusion. After combining data from two Randomized Controlled Trials it can be concluded that there is no clinical benefit for ACDA, when compared with ACDF or ACD 2 years after surgery. Preliminary subgroup analysis indicated outcomes were similar between treatment groups, and that no subgroup could be appointed that benefited more from either ACD, ACDF, or ACDA.

Funder: Max-Planck-Gesellschaft (Max Planck Society); doi: https://doi.org/10.13039/501100004189, Funder: Max Planck Society Innovation Fund Heinz L. Krekeler Foundation, Much like humans, chimpanzees occupy diverse habitats and exhibit extensive behavioural variability. However, chimpanzees are recognized as a discontinuous species, with four subspecies separated by historical geographic barriers. Nevertheless, their range-wide degree of genetic connectivity remains poorly resolved, mainly due to sampling limitations. By analyzing a geographically comprehensive sample set amplified at microsatellite markers that inform recent population history, we found that isolation by distance explains most of the range-wide genetic structure of chimpanzees. Furthermore, we did not identify spatial discontinuities corresponding with the recognized subspecies, suggesting that some of the subspecies-delineating geographic barriers were recently permeable to gene flow. Substantial range-wide genetic connectivity is consistent with the hypothesis that behavioural flexibility is a salient driver of chimpanzee responses to changing environmental conditions. Finally, our observation of strong local differentiation associated with recent anthropogenic pressures portends future loss of critical genetic diversity if habitat fragmentation and population isolation continue unabated.

Paleoclimate reconstructions have enhanced our understanding of how past climates have shaped present-day biodiversity. We hypothesize that the geographic extent of Pleistocene forest refugia and suitable habitat fluctuated significantly in time during the late Quaternary for chimpanzees (Pan troglodytes). Using bioclimatic variables representing monthly temperature and precipitation estimates, past human population density data, and an extensive database of georeferenced presence points, we built a model of changing habitat suitability for chimpanzees at fine spatio-temporal scales dating back to the Last Interglacial (120,000 BP). Our models cover a spatial resolution of 0.0467 degrees (approximately 5.19 km(2) grid cells) and a temporal resolution of between 1000 and 4000 years. Using our model, we mapped habitat stability over time using three approaches, comparing our modeled stability estimates to existing knowledge of Afrotropical refugia, as well as contemporary patterns of major keystone tropical food resources used by chimpanzees, figs (Moraceae), and palms (Arecacae). Results show habitat stability congruent with known glacial refugia across Africa, suggesting their extents may have been underestimated for chimpanzees, with potentially up to approximately 60,000 km(2) of previously unrecognized glacial refugia. The refugia we highlight coincide with higher species richness for figs and palms. Our results provide spatio-temporally explicit insights into the role of refugia across the chimpanzee range, forming the empirical foundation for developing and testing hypotheses about behavioral, ecological, and genetic diversity with additional data. This methodology can be applied to other species and geographic areas when sufficient data are available.