Efficacy of pain management strategies in adults with Amyotrophic Lateral Sclerosis (ALS): A Systematic Review.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive muscle weakness. Presence of pain in ALS patients is heterogeneously reported in studies, and mostly underrepresented in symptom scales. The aim of this study is to evaluate the efficacy of pharmacological and non-pharmacological therapeutic modalities for pain management in patients with ALS. A systematic review was conducted in four databases; PubMed, Scopus, Clinicaltrials.gov, and Cochrane-Ovid. Five randomized controlled clinical trials were included regarding pharmacological and non-pharmacological pain management interventions in adult patients with confirmed diagnosis of ALS in whom pain was objectively evaluated. Risk of bias assessment was evaluated using the RoB2.0 tool. Eligible studies were reported as a descriptive analysis. This systematic review was registered with PROSPERO ID: CRD42024495009. Five clinical trials regarding pain management strategies in ALS were eligible for analysis. Two out of five were non-pharmacological approaches whilst the remaining three provided pharmacological therapies. Of these, Mexiletine was efficient in terms of pain relief, particularly between 600 and 900 mg per day, whereas Mecasin showed no pain relief at both, high and low doses. Non-pharmacological therapies, such as exercise and osteopathic manual treatment also lacked efficacy in regard to pain management. Clinical trials focusing on pain management strategies for ALS patients are limited. Medical professionals, understandably focused on immediate life-threatening aspects, may inadvertently sideline the nuanced and intricate dimension of pain experienced by patients with ALS.

The association between vertebral endplate defects, subchondral bone marrow changes, and lumbar intervertebral disc degeneration: a retrospective, 3-year longitudinal study.

PURPOSE: To investigate the influence of vertebral endplate defects and subchondral bone marrow changes on the development of lumbar intervertebral disc degeneration (DD). METHODS: Patients > 18 y/o without any history of lumbar fusion who had repeat lumbar magnetic resonance imaging scans primarily for low back pain (LBP) performed at a minimum of 3 years apart at a single institution, and no spinal surgery in between scans were included. Total endplate score (TEPS), Modic changes (MC), and Pfirrmann grading (PFG) per lumbar disc level were assessed. DD was defined as PFG ≥ 4. RESULTS: Three hundred and fifty-three patients (54.4% female) were included in the final analysis, comprising 1765 lumbar intervertebral discs. The patient population was 85.6% Caucasian with a median age of 60.1 years and a body mass index (BMI) of 25.8 kg/m2. A cutoff score of 5 was identified for the TEPS above which both the prevalence of DD and the odds of developing DD increased. The probability of developing DD did not differ significantly between lumbar disc levels (P = 0.419). In the multivariable analysis with adjustments for age, sex, race, body mass index (BMI), MC, TEPS cutoff > 5, and spinal level, only age (OR = 1.020; P = 0.002) was found to be an independent risk factor for developing intervertebral DD. CONCLUSION: Our results suggest that TEPS does not unequivocally predict intervertebral DD in patients with LBP, since higher degrees of endplate defects might also develop secondarily to DD, and MC tend to occur late in the cascade of degeneration.

Predictors of adverse events after endoscopic ultrasound-guided through-the-needle biopsy of pancreatic cysts: a recursive partitioning analysis.

BACKGROUND AND STUDY AIMS : Endoscopic ultrasound-guided through-the-needle biopsy (TTNB) of pancreatic cystic lesions (PCLs) is associated with a non-negligible risk for adverse events (AEs). We aimed to identify the hierarchic interaction among independent predictors for TTNB-related AEs and to generate a prognostic model using recursive partitioning analysis (RPA). PATIENTS AND METHODS : Multicenter retrospective analysis of 506 patients with PCLs who underwent TTNB. RPA of predictors for AEs was performed and the model was validated by means of bootstrap resampling. RESULTS : Mean cysts size was 36.7 mm. Most common diagnoses were intraductal papillary mucinous neoplasm (IPMN, 45 %), serous cystadenoma (18.8 %), and mucinous cystadenoma (12.8 %). Fifty-eight (11.5 %) AEs were observed. At multivariate analysis, age (odds ratio [OR] 1.32, 1.09-2.14; p = 0.05), number of TTNB passes (OR from 2.17, 1.32-4.34 to OR 3.16, 2.03-6.34 with the increase of the number of passes), complete aspiration of the cyst (OR 0.56, 0.31-0.95; p = 0.02), and diagnosis of IPMN (OR 4.16, 2.27-7.69; p < 0.001) were found to be independent predictors of AEs, as confirmed by logistic regression and random forest analyses. RPA identified three risk classes: high-risk (IPMN sampled with multiple microforceps passes, 28 % AEs rate), low-risk (1.4 % AE rate, including patients < 64 years with other-than-IPMN diagnosis sampled with ≤ 2 microforceps passes and with complete aspiration of the cyst) and middle-risk class (6.1 % AEs rate, including the remaining patients). CONCLUSION : TTNB should be selectively used in the evaluation of patients with IPMN. The present model could be applied during patient selection as to optimize the benefit/risk of TTNB.

Loss of postnatal quiescence of neural stem cells through mTOR activation upon genetic removal of cysteine string protein-α.

Neural stem cells continuously generate newborn neurons that integrate into and modify neural circuitry in the adult hippocampus. The molecular mechanisms that regulate or perturb neural stem cell proliferation and differentiation, however, remain poorly understood. Here, we have found that mouse hippocampal radial glia-like (RGL) neural stem cells express the synaptic cochaperone cysteine string protein-α (CSP-α). Remarkably, in CSP-α knockout mice, RGL stem cells lose quiescence postnatally and enter into a high-proliferation regime that increases the production of neural intermediate progenitor cells, thereby exhausting the hippocampal neural stem cell pool. In cell culture, stem cells in hippocampal neurospheres display alterations in proliferation for which hyperactivation of the mechanistic target of rapamycin (mTOR) signaling pathway is the primary cause of neurogenesis deregulation in the absence of CSP-α. In addition, RGL cells lose quiescence upon specific conditional targeting of CSP-α in adult neural stem cells. Our findings demonstrate an unanticipated cell-autonomic and circuit-independent disruption of postnatal neurogenesis in the absence of CSP-α and highlight a direct or indirect CSP-α/mTOR signaling interaction that may underlie molecular mechanisms of brain dysfunction and neurodegeneration.

Characterization and Potential Relevance of Randomized Controlled Trial Patient Populations in Total Joint Arthroplasty in the United States: A Systematic Review.

BACKGROUND: A substantial number of randomized controlled trial (RCT) studies in total joint arthroplasty (TJA) are published each year in the United States (US). However, it is unknown how closely the demographic and clinical characteristics of these cohorts resemble that of the US patient population undergoing TJA. Thus, the purpose of this systematic review was to evaluate the patient characteristics of published RCTs in TJA in the US and to compare these characteristics against patient cohorts from national patient databases. METHODS: RCT studies regarding primary TJA conducted in the US were selected. Key patient demographics were aggregated and compared against demographics characteristics of the Healthcare Cost and Utilization Project of the Agency for Healthcare Research and Quality National Inpatient Sample (NIS) and American College of Surgeons National Surgical Quality Improvement Program patient cohorts. RESULTS: One hundred and fifty-three RCTs fulfilled the inclusion criteria and were included. The total number of patients in the 153 RCTs was 24,135 patients. The average age of patients in the TJA RCT cohort was 65 years (53-80) while the NIS cohort was 67 years (18-90) (d = 0.21, effect size = small). The average body mass index of the TJA RCT cohort was 30.8 (18.2-37.6) while the National Surgical Quality Improvement Program cohort was 31.9 (14.1-59.6) (d = 0.18, effect size = small). For TJA, effect sizes for age, body mass index BMI, sex, ethnicity, smoking, and diabetes were all small or very small. CONCLUSION: Overall, the US RCT patient cohort for TJA does not differ substantially from the general patient population undergoing TJA in the United States. Differences in demographic and clinical characteristics between the TJA RCT cohort and database cohorts ranged from minimal to small, suggesting that these differences are unlikely to impact clinical outcomes.

Towards an Efficient Identification Process for Large-Scale RFID Systems ‡.

Radio Frequency Identification (RFID) is one of the most widely used wireless communications technologies nowadays. Among the numerous processes executed within an RFID system, the identification processis the most important one. There have been several proposals to efficiently execute such a mechanism, which are based on the use of an RFID identification method. Besides, one of the most studied scenarios comprises one reader and a set of RFID tags, which we call the centralized approach. Recent work shows that executing the identification process in a distributed or parallel way may be of great benefit for applications with high requirements on time and resources usage, i.e., applications where the time required to execute the identification process needs to be low. In this paper, we focus is on large RFID systems and compare two identification mechanisms, one based on the centralized approach and the other based on the distributed approach. Our aim is to find the advantages and disadvantages of each approach for general RFID scenarios. We observe that the distributed approach is very promising compared to the traditional approach since considerable improvements are found in identification delay, and also the implementation costs would be highly reduced.

Chronic Pelvic Pain Development and Prostate Inflammation in Strains of Mice With Different Susceptibility to Experimental Autoimmune Prostatitis.

BACKGROUND: Experimental autoimmune prostatitis (EAP) is an autoimmune inflammatory disease of the prostate characterized by peripheral prostate-specific autoimmune responses associated with prostate inflammation. EAP is induced in rodents upon immunization with prostate antigens (PAg) plus adjuvants and shares important clinical and immunological features with the human disease chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). METHODS: EAP was induced in young NOD, C57BL/6, and BALB/c male mice by immunization with PAg plus complete Freund́s adjuvant. Tactile allodynia was assessed using Von Frey fibers as a measure of pelvic pain at baseline and at different time points after immunization. Using conventional histology, immunohistochemistry, FACS analysis, and protein arrays, an interstrain comparative study of prostate cell infiltration and inflammation was performed. RESULTS: Chronic pelvic pain development was similar between immunized NOD and C57BL/6 mice, although the severity of leukocyte infiltration was greater in the first case. Coversely, minimal prostate cell infiltration was observed in immunized BALB/c mice, who showed no pelvic pain development. Increased numbers of mast cells, mostly degranulated, were detected in prostate samples from NOD and C57BL/6 mice, while lower total counts and resting were observed in BALB/c mice. Prostate tissue from NOD mice revealed markedly increased expression levels of inflammatory cytokines, chemokines, adhesion molecules, vascular endothelial growth factor, and metalloproteinases. Similar results, but to a lesser extent, were observed when analyzing prostate tissue from C57BL/6 mice. On the contrary, the expression of the above mediators was very low in prostate tissue from immunized BALB/c mice, showing significantly slight increments only for CXCL1 and IL4. CONCLUSIONS: Our results provide new evidence indicating that NOD, C57BL/6, and BALB/c mice develop different degrees of chronic pelvic pain, type, and amount of prostate cell infiltration and secretion of inflammatory mediators. Our results corroborate and support the notion that mice with different genetic background have different susceptibility to EAP induction. Prostate 77:94-104, 2017. © 2016 Wiley Periodicals, Inc.

Chronic Infection of the Prostate by Chlamydia muridarum Is Accompanied by Local Inflammation and Pelvic Pain Development.

BACKGROUND: Chlamydia trachomatis urogenital infections are the leading cause of sexually transmitted bacterial infections. Although the prevalence of chlamydial infection is similar in men and women, current research is mainly focused on women, neglecting the study of male genital tract infections. We, therefore, investigated Chlamydia infection in the rodent male genital tract. MATERIALS AND METHODS: Male NOD and C57BL/6 mice were inoculated in the meatus urethra with C. muridarum. Bacterial DNA, leukocyte infiltration of male genital tract tissues, pelvic pain, and Chlamydia-specific immune responses were analyzed at different time points. RESULTS AND CONCLUSIONS: The inoculation of C. muridarum in the meatus urethra of male mice resulted in an ascending and widely disseminated infection of the male genital tract. C. muridarum remained longer and with the highest bacterial burdens in the prostate, thus showing a special tropism for this organ. Infection caused leukocyte infiltration, mainly composed by neutrophils, and also induced early pelvic pain development that rapidly dropped and resolved as the infection became chronic. Bacterial load and leukocyte infiltration was observed in all prostate lobes, although dorsolateral prostate was the most affected lobe. Interestingly, immune responses induced by both mice strains were characterized by the production of high levels of IL-10 during early stages of the infection, with highest and sustained levels observed in NOD mice, which showed to be less efficient in clearing the infection. Chronic infection of the prostate accompanied by local inflammation and pelvic pain development described herein have important implications for the improvement of the diagnosis and for the design of new efficient therapies. Prostate 77:517-529, 2017. © 2017 Wiley Periodicals, Inc.

Male genital tract immune response against Chlamydia trachomatis infection.

Chlamydia trachomatis is the most commonly reported agent of sexually transmitted bacterial infections worldwide. This pathogen frequently leads to persistent, long-term, subclinical infections, which in turn may cause severe pathology in susceptible hosts. This is in part due to the strategies that Chlamydia trachomatis uses to survive within epithelial cells and to evade the host immune response, such as subverting intracellular trafficking, interfering signaling pathways and preventing apoptosis. Innate immune receptors such as toll-like receptors expressed on epithelial and immune cells in the genital tract mediate the recognition of chlamydial molecular patterns. After bacterial recognition, a subset of pro-inflammatory cytokines and chemokines are continuously released by epithelial cells. The innate immune response is followed by the initiation of the adaptive response against Chlamydia trachomatis, which in turn may result in T helper 1-mediated protection or in T helper 2-mediated immunopathology. Understanding the molecular mechanisms developed by Chlamydia trachomatis to avoid killing and host immune response would be crucial for designing new therapeutic approaches and developing protective vaccines. In this review, we focus on chlamydial survival strategies and the elicited immune responses in male genital tract infections.

[Effectiveness of an individualised physiotherapy program versus group therapy on neck pain and disability in patients with acute and subacute mechanical neck pain]. / Eficacia ante el dolor y la discapacidad cervical de un programa de fisioterapia individual frente a uno colectivo en la cervicalgia mecánica aguda y subaguda.

OBJECTIVE: To compare the efficacy in reducing neck pain and disability in an individualised physiotherapy treatment with group treatment in acute and subacute mechanical neck pain. DESIGN: Randomised clinical trial. LOCATION: Health Area of University Hospital Virgen del Rocío, Seville, Spain. PARTICIPANTS: A total of 90 patients diagnosed with mechanical neck pain of up to one month onset, distributed randomly into two groups: (i)individualised treatment; (ii)group treatment. INTERVENTION: The treatment consisted of 15 sessions of about 60minutes for both groups. Individual treatment consisted of 15minutes of infrared heat therapy, 17minutes of massage, and analytical passive stretching of the trapezius muscles and angle of the scapula. The group treatment consisted of a program of active mobilisation, isometric contractions, self-stretching, and postural recommendations. MAIN MEASURES: Pain was measured at the beginning and end of treatment pain using a Visual Analogue Scale (VAS) and an algometer applied on the trapezius muscles and angle of the scapula, and neck disability using the Neck Disability Index. RESULTS: Both treatments were statistically significant (P<.001) in improving all variables. Statistically significant differences (P<.001) were found for all of them in favour of individualised treatment compared to group treatment. CONCLUSIONS: Patients with acute or subacute mechanical neck pain experienced an improvement in pain and neck disability after receiving either of the physiotherapy treatments used in our study, with the individual treatment being more effective than collective.

Expression of CXCR3 on specific T cells is essential for homing to the prostate gland in an experimental model of chronic prostatitis/chronic pelvic pain syndrome.

Experimental autoimmune prostatitis (EAP) is considered a valid model for the human disease chronic prostatitis/chronic pelvic pain syndrome. In this report, we analyzed phenotypic characteristics of T cells that gain access to the prostate and induce leukocyte recruitment in mice with different susceptibility to EAP. After EAP induction, NOD mice developed a specific cellular response characterized by a mixed Th1/Th17 pattern with specific T cells mainly expressing CXCR3 that infiltrated and damaged the prostate. In contrast, BALB/c mice, as well as NOD-IFN-γ(-/-), exhibited only Th17 cells mainly expressing CCR6 that were not capable of infiltrating the prostate gland. Adoptive transfer experiments of T cells from NOD or NOD-IFN-γ(-/-) mice to NOD-SCID recipients showed that only T cells from NOD mice successfully infiltrated the prostate. However, after "in vitro" or "in vivo" treatment with rIFN-γ, T cells from NOD-IFN-γ(-/-) mice became capable of homing to the prostate and induced leukocyte recruitment. Chemokine levels in prostate tissue from NOD mice showed increased expression levels of CXCR3 ligands. Additional experiments using adoptive transfer of sorted CXCR3(+)CD3(+) T cells or administrating a CXCR3 antagonist treatment confirmed these previous results. Altogether, our results demonstrate that the expression of CXCR3 on effector T cells is essential for their homing to the prostate gland in EAP. CXCR3 emerges as a potential therapeutic target to control chronic prostatitis/chronic pelvic pain syndrome.

Bio-efficacy of the essential oil of oregano (Origanum vulgare Lamiaceae. Ssp. Hirtum).

The aim of this study was to investigate the bioactivity of the essential oil isolated from Origanum vulgare L. (EOv). We analyzed the in vivo anti-inflammatory properties in a mouse-airway inflammation model and the in vitro antimicrobial activity, genotoxicity over the anaphase-telophase with the Allium cepa strain and its cytotoxicity/viability in A549 culture cells. In vivo, EOv modified the levels of tumor necrosis factor -α and viable activated macrophages and was capable to mitigate the effects of degradation of conjugated dienes. In vitro, EOv reduced the viability of cultured A549 cells as well as the mitotic index and a number of chromosomal aberrations; however, it did not change the number of phases. We found that EOv presents antimicrobial activity against different Gram (-) and (+) strains, measured by disc-diffusion test and confirmed with a more accurate method, the AutoCad software. We postulate that EOv presents antibacterial, antioxidant and chemopreventive properties and could be play an important role as bioprotector agent.

Driving valence-specific behavior through single-cell resolution control in the amygdala.

In this issue of Neuron, Piantadosi et al.1 demonstrate that by precisely controlling the activity of individual negative-valence neurons and positive-valence neurons in the basolateral amygdala, one can alter animals' appetitive or aversive responses, respectively, establishing a causal role of these neurons in valence-specific behavior.

The Impact of the COVID-19 Pandemic on Ambulatory Lumbar Spine Decompression Surgery.

Background Only a few studies have examined the impact of the coronavirus disease 2019 pandemic on spine ambulatory surgeries and changes in trends. Therefore, we investigated trends during the pre-pandemic period and three pandemic stages in patients undergoing lumbar decompression procedures in the ambulatory surgery (AMS) setting. Methodology A total of 2,670 adult patients undergoing one- or two-level lumbar decompression surgery were retrospectively reviewed. Patients were categorized into the following four groups: 1: pre-pandemic (before the pandemic from January 1, 2019, to March 16, 2020); 2: restricted period (when elective surgery was canceled from March 17, 2020, to June 30, 2020); 3: post-restricted 2020 (July 1, 2020, to December 31, 2020, before vaccination); and 4: post-restricted 2021 (January 1, 2021 to December 31, 2021 after vaccination). Simple and multivariable logistic regression analyses as well as retrospective interrupted time series (ITS) analysis were conducted comparing AMS patients in the four periods. Results Patients from the restricted pandemic period were younger and healthier, which led to a shorter length of stay (LOS). The ITS analysis demonstrated a significant drop in mean LOS at the beginning of the restricted period and recovered to the pre-pandemic levels in one year. Multivariable logistic regression analyses indicated that the pandemic was an independent factor influencing the LOS in post-restricted phases. Conclusions As the post-restricted 2020 period itself might be independently influenced by the pandemic, these results should be taken into account when interpreting the LOS of the patients undergoing ambulatory spine surgery in post-restricted phases.

The Reciprocal Relationship Between Lumbar Intervertebral Disc Degeneration and the MRI-Based Vertebral Bone Quality Score.

STUDY DESIGN: Retrospective longitudinal study. OBJECTIVE: To investigate the association between lumbar intervertebral disc degeneration (DD) and the vertebral bone quality (VBQ) score. SUMMARY OF BACKGROUND DATA: The VBQ score that is based on magnetic resonance imaging (MRI) has been proposed as a measure of lumbar spine bone quality and is a significant predictor of healthy versus osteoporotic bone. However, the role of segmental contributing factors on VBQ is unknown. METHODS: Non-surgical patients who underwent repeated lumbar MRI scans, at least three years apart primarily for low back pain were retrospectively included. VBQ was assessed as previously described. DD was assessed using the Pfirrmann grading (PFG) scale. PFG grades were summarized as PFGL1-4 for the upper three lumbar disc levels, as PFGL4-S1 for the lower two lumbar disc levels, and as PFGL1-S1 for all lumbar disc levels. Multivariable linear mixed models were used with adjustments for age, sex, race, body mass index (BMI), and the clustering of repeated measurements. RESULTS: 350 patients (54.6% female, 85.4% Caucasian) were included in the final analysis, with a median age at baseline of 60.1 years and a BMI of 25.8 kg/m2. VBQ significantly increased from 2.28 at baseline to 2.36 at follow-up (P = 0.001). In the unadjusted analysis, a significant positive correlation was found between PFGL1-4, PFGL1-S1, and VBQ at baseline (P < 0.05) that increased over time (P < 0.005). In the adjusted multivariable analysis, PFGL1-4 (ß = -0.0195; P = 0.021), PFGL4-S1 (ß = -0.0310; P = 0.007), and PFGL1-S1 (ß = -0.0160; P = 0.012) were independently and negatively associated with VBQ. CONCLUSION: More advanced and long-lasting DD is associated with lower VBQ indicating less bone marrow fat content and potentially stronger bone. VBQ score as a marker of bone quality seems affected by DD.

Correlation between MRI-based spinal muscle parameters and the vertebral bone quality score in lumbar fusion patients.

Introduction: The vertebral bone quality (VBQ) score that is based on non-contrast enhanced T1-weighted MRI was recently introduced as a novel measure of bone quality in the lumbar spine and shown to be a significant predictor of healthy versus osteopenic/osteoporotic bone. Research question: This study aimed to assess possible correlations between the VBQ score and the functional cross-sectional area (FCSA) of psoas and lumbar spine extensor muscles. Material and methods: Patients who underwent fusion surgery between 2014 and 2017 and had lumbar MRI and CT scans within 6 months prior to surgery were included. The FCSA was assessed at L3-L5 using a pixel intensity threshold method. The VBQ score was calculated by dividing the signal intensity (SI) of the vertebrae L1-L4 through the SI of the cerebrospinal fluid at L3. Volumetric bone mineral density (vBMD) was assessed by quantitative CT. Results: 80 patients (58.8% female, median age 68.8 years) were included. Overall prevalence of osteopenia/osteoporosis was 66.3%, with no significant differences between men and women. The mean (SD) VBQ score was significantly smaller in men, at 2.26 (0.45) versus women at 2.59 (0.39) (p = 0.001). After adjusting for age and BMI, a significant negative correlation was seen between the VBQ score and psoas FCSA at L3 (ß = -0.373; p = 0.022), but only in men. Conclusion: Our results highlight sex differences in the VBQ score that were not demonstrated by vBMD and suggest a potential role of this novel measure to assess not only bone quality, but also spinal muscle quantity.

Risk Factors for Ambulatory Surgery Conversion to Extended Stay Among Patients Undergoing One-level or Two-level Posterior Lumbar Decompression.

STUDY DESIGN: A retrospective observational study. OBJECTIVE: The objective of this study was to investigate the factors associated with the conversion of patient status from ambulatory surgery (AMS) to observation service (OS) (<48 h) or inpatient (>48 h). SUMMARY OF BACKGROUND DATA: AMS is becoming increasingly common in the United States because it is associated with a similar quality of care compared with inpatient surgery, significant costs reduction, and patients' desire to recuperate at home. However, there are instances when AMS patients may be subjected to extended hospital stays. Unanticipated extension of hospitalization stays can be a great burden not only to patients but to medical providers and insurance companies alike. MATERIALS AND METHODS: Data from 1096 patients who underwent one-level or two-level lumbar decompression AMS at an in-hospital, outpatient surgical facility between January 1, 2019, and March 16, 2020, were collected. Patients were categorized into three groups based on length of stay: (1) AMS, (2) OS, or (3) inpatient. Demographics, comorbidities, surgical information, and administrative information were collected. Simple and multivariable logistic regression analyses were conducted comparing AMS patients and OS/inpatient as well as OS and inpatients. RESULTS: Of the 1096 patients, 641 (58%) patients were converted to either OS (n=486) or inpatient (n=155). The multivariable analysis demonstrated that age (more than 80 yr old), high American Society of Anesthesiologists Physical Status (ASA) grade, history of sleep apnea, drain use, high estimated blood loss, long operation, late operation start time, and a high pain score were considered independent risk factors for AMS conversion to OS/inpatient. The risk factors for OS conversion to inpatient were an ASA class 3 or higher, coronary artery disease, diabetes mellitus, hypothyroidism, steroid use, drain use, dural tear, and laminectomy. CONCLUSIONS: Several surgical factors along with patient-specific factors were significantly associated with AMS conversion. Addressing modifiable surgical factors might reduce the AMS conversion rate and be beneficial to patients and facilities.

Examining the Role of Paraspinal Musculature in Post-Operative Disability after Lumbar Fusion Surgery for Degenerative Spondylolisthesis.

STUDY DESIGN: Retrospective analysis of prospectively enrolled patients. OBJECTIVE: To evaluate the relationship between paraspinal muscle (PM) atrophy and Oswestry Disability Index (ODI) improvement after spinal fusion surgery for degenerative lumbar spondylolisthesis (DLS). BACKGROUND: Atrophy of the PM is linked to multiple spinal conditions, sagittal malalignment, and increased postoperative complications. However, only limited evidence for the effect on patient-reported outcomes exists. METHODS: Patients with DLS undergoing decompression and fusion surgery were analyzed. Patients with missing follow-up, no imaging, or inadequate image quality were excluded. The Oswestry Disability Index (ODI) was assessed preoperatively and two years postoperatively. A cross-sectional area of the PM was measured on a T2-weighted Magnetic Resonance Imaging (MRI) sequence at the upper endplate of L4. Based on the literature, a 10-point improvement cut-off was defined as the minimum clinically important difference (MCID). Patients with a baseline ODI below the MCID were excluded. Logistic regression was used to calculate the association between fatty infiltration (FI) of the PM and improvement in ODI, adjusted for age, sex, and body mass index (BMI). RESULTS: 133 patients were included in the final analysis, with only two lost to follow-up. The median age was 68 years (IQR 62 - 73). The median preoperative ODI was 23 (IQR 17 - 28), and 76.7% of patients showed improvement in their ODI score by at least 10 points. In the multivariable regression, FI of the erector spinae and multifidus increased the risk of not achieving clinically relevant ODI improvement (P=0.01 and P<0.001, respectively). No significant association was found for the psoas muscle (P=0.158). CONCLUSIONS: This study demonstrates that FI of the erector spinae and multifidus, is significantly associated with less likelihood of clinically relevant ODI improvement following decompression and fusion. Further research is needed to assess the effect of interventions.

Development of Antiepileptic Drugs throughout History: From Serendipity to Artificial Intelligence.

This article provides a comprehensive narrative review of the history of antiepileptic drugs (AEDs) and their development over time. Firstly, it explores the significant role of serendipity in the discovery of essential AEDs that continue to be used today, such as phenobarbital and valproic acid. Subsequently, it delves into the historical progression of crucial preclinical models employed in the development of novel AEDs, including the maximal electroshock stimulation test, pentylenetetrazol-induced test, kindling models, and other animal models. Moving forward, a concise overview of the clinical advancement of major AEDs is provided, highlighting the initial milestones and the subsequent refinement of this process in recent decades, in line with the emergence of evidence-based medicine and the implementation of increasingly rigorous controlled clinical trials. Lastly, the article explores the contributions of artificial intelligence, while also offering recommendations and discussing future perspectives for the development of new AEDs.

Increased neurotransmitter release at the neuromuscular junction in a mouse model of polyglutamine disease.

In Huntington's disease (HD), the expansion of polyglutamine (polyQ) repeats at the N terminus of the ubiquitous protein huntingtin (htt) leads to neurodegeneration in specific brain areas. Neurons degenerating in HD develop synaptic dysfunctions. However, it is unknown whether mutant htt impacts synaptic function in general. To investigate that, we have focused on the nerve terminals of motor neurons that typically do not degenerate in HD. Here, we have studied synaptic transmission at the neuromuscular junction of transgenic mice expressing a mutant form of htt (R6/1 mice). We have found that the size and frequency of miniature endplate potentials are similar in R6/1 and control mice. In contrast, the amplitude of evoked endplate potentials in R6/1 mice is increased compared to controls. Consistent with a presynaptic increase of release probability, synaptic depression under high-frequency stimulation is higher in R6/1 mice. In addition, no changes were detected in the size and dynamics of the recycling synaptic vesicle pool. Moreover, we have found increased amounts of the synaptic vesicle proteins synaptobrevin 1,2/VAMP 1,2 and cysteine string protein-α, and the SNARE protein SNAP-25, concomitant with normal levels of other synaptic vesicle markers. Our results reveal that the transgenic expression of a mutant form of htt leads to an unexpected gain of synaptic function. That phenotype is likely not secondary to neurodegeneration and might be due to a primary deregulation in synaptic protein levels. Our findings could be relevant to understand synaptic toxic effects of proteins with abnormal polyQ repeats.