Long-Term Pain Characteristics and Management Following Minimally Invasive Spinal Decompression and Open Laminectomy and Fusion for Spinal Stenosis.

Background and Objectives: To compare the long-term pain characteristics and its chronic management following minimally invasive spinal (MIS) decompression and open laminectomy with fusion for lumbar stenosis. Materials and Methods: The study cohort included patients with a minimum 5-year postoperative follow-up after undergoing either MIS decompression or laminectomy with fusion for spinal claudication. The primary outcome of interest was chronic back and leg pain intensity. Secondary outcome measures included pain frequency during the day, chronic use of non-opioid analgesics, narcotic medications, medical cannabinoids, and continuous interventional pain treatments. Results: A total of 95 patients with lumbar spinal stenosis underwent one- or two-level surgery for lumbar spinal stenosis between April 2009 and July 2013. Of these, 50 patients underwent MIS decompression and 45 patients underwent open laminectomy with instrumented fusion. In the fusion group, a higher percentage of patients experienced moderate-to-severe back pain with 48% compared to 21.8% of patients in the MIS decompression group (p < 0.01). In contrast, we found no significant difference in the reported leg pain in both groups. In the fusion group, 20% of the patients described their back and leg pain as persistent throughout the day compared to only 2.2% in the MIS decompression group (p < 0.05). A trend toward higher chronic dependence on analgesic medication and repetitive pain clinic treatments was found in the fusion group. Conclusions: MIS decompression for the treatment of degenerative spinal stenosis resulted in decreased long-term back pain and similar leg pain outcomes compared to open laminectomy and instrumented fusion surgery.

Chromosome 7 to the rescue: overcoming chromosome 10 loss in gliomas.

The co-occurrence of chromosome 10 loss and chromosome 7 gain in gliomas is the most frequent loss-gain co-aneuploidy pair in human cancers, a phenomenon that has been investigated without resolution since the late 1980s. Expanding beyond previous gene-centric studies, we investigate the co-occurrence in a genome-wide manner taking an evolutionary perspective. First, by mining large tumor aneuploidy data, we predict that the more likely order is 10 loss followed by 7 gain. Second, by analyzing extensive genomic and transcriptomic data from both patients and cell lines, we find that this co-occurrence can be explained by functional rescue interactions that are highly enriched on 7, which can possibly compensate for any detrimental consequences arising from the loss of 10. Finally, by analyzing transcriptomic data from normal, non-cancerous, human brain tissues, we provide a plausible reason why this co-occurrence happens preferentially in cancers originating in certain regions of the brain.

A single-center real-life study on the use of medical cannabis in patients with dystonia.

Background: While cannabis-based medicine is being commonly used in patients with movement disorders, there is a scarcity of publications regarding the effect of cannabis on dystonia. We aimed to describe medical cannabis use in patients with dystonia and related pain. Methods: We employed a structured interview to obtain data on the cannabis treatment regimen, perception of effectiveness and side effect profile. Eligible participants were patients diagnosed with dystonia from the movement disorders unit at the Tel-Aviv Medical Center who had used licensed medical cannabis between January 2019 and January 2021. Results: Twenty-three subjects were interviewed (11 women, mean age 52.7). The most common way of administration was smoking (n = 11). Following an average of 2.5 ± 2.9 years of use, those with widespread dystonia (generalized, hemi and multifocal, n = 11) self-reported on a numeric rating scale an average 63% (range 0%-100%) reduction in symptoms of dystonia, while those with more focal dystonia patterns reported a significantly lower treatment effect of 32%. Participants reported a positive impact in related pain and quality of life, with an average rating of 3.8 out of 5 (SD = 1.2, median = 4) and 3.6 out of 5 (SD = 1.15, median = 4), respectively. Most common side effects were dry mouth (65%), sedation (43%), dizziness (39%) and psychiatric disorders (26%). Three patients (13%) discontinued therapy. Conclusion: A subset of dystonia patients who use medical cannabis under clinical observation reported significant subjective improvement during 30 months of use in average. Further prospective randomized controlled trials are required to examine the effectiveness of cannabis in dystonia.

Whole-Genome Duplication Shapes the Aneuploidy Landscape of Human Cancers.

Aneuploidy is a hallmark of cancer with tissue-specific prevalence patterns that suggest it plays a driving role in cancer initiation and progression. However, the contribution of aneuploidy to tumorigenesis depends on both cellular and genomic contexts. Whole-genome duplication (WGD) is a common macroevolutionary event that occurs in more than 30% of human tumors early in tumorigenesis. Although tumors that have undergone WGD are reported to be more permissive to aneuploidy, it remains unknown whether WGD also affects aneuploidy prevalence patterns. Here we analyzed clinical tumor samples from 5,586 WGD- tumors and 3,435 WGD+ tumors across 22 tumor types and found distinct patterns of aneuploidy in WGD- and WGD+ tumors. WGD+ tumors were characterized by more promiscuous aneuploidy patterns, in line with increased aneuploidy tolerance. Moreover, the genetic interactions between chromosome arms differed between WGD- and WGD+ tumors, giving rise to distinct cooccurrence and mutual exclusivity aneuploidy patterns. The proportion of whole-chromosome aneuploidy compared with arm-level aneuploidy was significantly higher in WGD+ tumors, indicating distinct dominant mechanisms for aneuploidy formation. Human cancer cell lines successfully reproduced these WGD/aneuploidy interactions, confirming the relevance of studying this phenomenon in culture. Finally, induction of WGD and assessment of aneuploidy in isogenic WGD-/WGD+ human colon cancer cell lines under standard or selective conditions validated key findings from the clinical tumor analysis, supporting a causal link between WGD and altered aneuploidy landscapes. We conclude that WGD shapes the aneuploidy landscape of human tumors and propose that this interaction contributes to tumor evolution. SIGNIFICANCE: These findings suggest that the interactions between whole-genome duplication and aneuploidy are important for tumor evolution, highlighting the need to consider genome status in the analysis and modeling of cancer aneuploidy.

FOXM1 repression increases mitotic death upon antimitotic chemotherapy through BMF upregulation.

Inhibition of spindle microtubule (MT) dynamics has been effectively used in cancer treatment. Although the mechanisms by which MT poisons elicit mitotic arrest are fairly understood, efforts are still needed towards elucidating how cancer cells respond to antimitotic drugs owing to cytotoxicity and resistance side effects. Here, we identified the critical G2/M transcription factor Forkhead box M1 (FOXM1) as a molecular determinant of cell response to antimitotics. We found FOXM1 repression to increase death in mitosis (DiM) due to upregulation of the BCL-2 modifying factor (BMF) gene involved in anoikis, an apoptotic process induced upon cell detachment from the extracellular matrix. FOXM1 binds to a BMF intronic cis-regulatory element that interacts with both the BMF and the neighbor gene BUB1B promoter regions, to oppositely regulate their expression. This mechanism ensures that cells treated with antimitotics repress BMF and avoid DiM when FOXM1 levels are high. In addition, we show that this mechanism is partly disrupted in anoikis/antimitotics-resistant tumor cells, with resistance correlating with lower BMF expression but in a FOXM1-independent manner. These findings provide a stratification biomarker for antimitotic chemotherapy response.