The WDR11 complex is a receptor for acidic-cluster-containing cargo proteins.

Vesicle trafficking is a fundamental process that allows for the sorting and transport of specific proteins (i.e., "cargoes") to different compartments of eukaryotic cells. Cargo recognition primarily occurs through coats and the associated proteins at the donor membrane. However, it remains unclear whether cargoes can also be selected at other stages of vesicle trafficking to further enhance the fidelity of the process. The WDR11-FAM91A1 complex functions downstream of the clathrin-associated AP-1 complex to facilitate protein transport from endosomes to the TGN. Here, we report the cryo-EM structure of human WDR11-FAM91A1 complex. WDR11 directly and specifically recognizes a subset of acidic clusters, which we term super acidic clusters (SACs). WDR11 complex assembly and its binding to SAC-containing proteins are indispensable for the trafficking of SAC-containing proteins and proper neuronal development in zebrafish. Our studies thus uncover that cargo proteins could be recognized in a sequence-specific manner downstream of a protein coat.

Cockayne Syndrome Linked to Elevated R-Loops Induced by Stalled RNA Polymerase II during Transcription Elongation.

Mutations in the Cockayne Syndrome group B (CSB) gene cause cancer in mice, but premature aging and severe neurodevelopmental defects in humans. CSB, a member of the SWI/SNF family of chromatin remodelers, plays diverse roles in regulating gene expression and transcription-coupled nucleotide excision repair (TC-NER); however, these functions do not explain the distinct phenotypic differences observed between CSB-deficient mice and humans. During investigating Cockayne Syndrome-associated genome instability, we uncover an intrinsic mechanism that involves elongating RNA polymerase II (RNAPII) undergoing transient pauses at internal T-runs where CSB is required to propel RNAPII forward. Consequently, CSB deficiency retards RNAPII elongation in these regions, and when coupled with G-rich sequences upstream, exacerbates genome instability by promoting R-loop formation. These R-loop prone motifs are notably abundant in relatively long genes related to neuronal functions in the human genome, but less prevalent in the mouse genome. These findings provide mechanistic insights into differential impacts of CSB deficiency on mice versus humans and suggest that the manifestation of the Cockayne Syndrome phenotype in humans results from the progressive evolution of mammalian genomes.

Frontotemporal dementia-like disease progression elicited by seeded aggregation and spread of FUS.

RNA binding proteins have emerged as central players in the mechanisms of many neurodegenerative diseases. In particular, a proteinopathy of fused in sarcoma (FUS) is present in some instances of familial Amyotrophic lateral sclerosis (ALS) and about 10% of sporadic Frontotemporal lobar degeneration (FTLD). Here we establish that focal injection of sonicated human FUS fibrils into brains of mice in which ALS-linked mutant or wild-type human FUS replaces endogenous mouse FUS is sufficient to induce focal cytoplasmic mislocalization and aggregation of mutant and wild-type FUS which with time spreads to distal regions of the brain. Human FUS fibril-induced FUS aggregation in the mouse brain of humanized FUS mice is accelerated by an ALS-causing FUS mutant relative to wild-type human FUS. Injection of sonicated human FUS fibrils does not induce FUS aggregation and subsequent spreading after injection into naïve mouse brains containing only mouse FUS, indicating a species barrier to human FUS aggregation and its prion-like spread. Fibril-induced human FUS aggregates recapitulate pathological features of FTLD including increased detergent insolubility of FUS and TAF15 and amyloid-like, cytoplasmic deposits of FUS that accumulate ubiquitin and p62, but not TDP-43. Finally, injection of sonicated FUS fibrils is shown to exacerbate age-dependent cognitive and behavioral deficits from mutant human FUS expression. Thus, focal seeded aggregation of FUS and further propagation through prion-like spread elicits FUS-proteinopathy and FTLD-like disease progression.

The Role of Pelvic Compensation in Sagittal Balance and Imbalance: The Impact of Pelvic Compensation on Spinal Alignment and Clinical Outcomes Following Adult Spinal Deformity Surgery.

BACKGROUND AND OBJECTIVES: The Scoliosis Research Society (SRS)-Schwab system does not include a pelvic compensation (PC) subtype, potentially contributing to gaps in clinical characteristics and treatment strategy for deformity correction. It also remains uncertain as to whether PC has differing roles in sagittal balance (SB) or imbalance (SI) status. To compare radiological parameters and SRS-22r domains between patients with failed pelvic compensation (FPC) and successful pelvic compensation (SPC) based on preoperative SB and SI. METHODS: A total of 145 adult spinal deformity patients who received deformity correction were analyzed. Radiographic and clinical outcomes were collected for statistical analysis. Patients were classified into 4 groups based on the median value of PT/PI ratio (PTr) and the cutoff value of SB. Patients with low PTr and high PTr were defined as FPC and SPC, respectively. Radiographic and clinical characteristics of different groups were compared. RESULTS: Patients with SPC exhibited significantly greater improvements in lumbar lordosis, pelvic tilt, PTr, and T1 pelvic angle as compared to patients with FPC, irrespective of SB or SI. No apparent differences in any of SRS-22r domains were observed at follow-up when comparing the SB-FPC and SB-SPC patients. However, patients with SI-SPC exhibited significantly better function, self-image, satisfaction, and subtotal domains at follow-up relative to those with SI-FPC. When SI-FPC and SI-SPC patients were subdivided further based on the degree of PI-LL by adjusting for age, the postoperative function and self-image domains were significantly better in the group with overcorrection of PI-LL than undercorrection of PI-LL in SI-FPC patients. However, no differences in these SRS-22r scores were observed when comparing the subgroups in SI-SPC patients. CONCLUSION: Flexible pelvic rotation is associated with benefits to the correction of sagittal parameters, irrespective of preoperative SB or SI status. However, PC is only significantly associated with clinical outcomes under SI. Patients with SI-FPC exhibit poorer postoperative clinical outcomes, which should be recommended to minimize PI-LL.

Efficacy of using telecare services for community-dwelling people with diabetes: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the glycated hemoglobin (HbA1c), blood pressure, self-efficacy, and quality of life efficacy of using telecare services for community-dwelling people with diabetes. METHODS: Cochrane Library, Web of Science, PsycINFO, PubMed, EMBASE, CINAHL, and Scopus databases were systematically searched from their inception dates to June 22, 2023. Two evaluators independently selected and evaluated eligible studies. A protocol was registered in PROSPERO. RESULTS: An analysis of 17 studies that included 3586 subjects showed that telecare significantly improved the management of patients with diabetes. Compared to controls, intervention care had significant benefits regarding HbA1c (MD = -0.30, 95 % CI = -0.44 - -0.17, 16 studies), systolic blood pressure (MD = -2.45, 95 % CI = -4.53 - -0.36, P = 0.02), self-efficacy (MD = 0.36, 95 % CI = 0.04 - 0.67, P = 0.03) and quality of life (MD = 0.37, 95 % CI = 0.05 - 0.70, P = 0.02). However, diastolic blood pressure (MD = -1.37, 95 % CI = -3.34 - -0.61, P = 0.17) was not found to be significantly affected. CONCLUSIONS: Telecare is effective in improving self-management among community-dwelling people with diabetes, suggesting an effective means for them to achieve self-management.

Frontotemporal dementia-like disease progression elicited by seeded aggregation and spread of FUS.

RNA binding proteins have emerged as central players in the mechanisms of many neurodegenerative diseases. In particular, a proteinopathy of fu sed in s arcoma (FUS) is present in some instances of familial Amyotrophic lateral sclerosis (ALS) and about 10% of sporadic FTLD. Here we establish that focal injection of sonicated human FUS fibrils into brains of mice in which ALS-linked mutant or wild-type human FUS replaces endogenous mouse FUS is sufficient to induce focal cytoplasmic mislocalization and aggregation of mutant and wild-type FUS which with time spreads to distal regions of the brain. Human FUS fibril-induced FUS aggregation in the mouse brain of humanized FUS mice is accelerated by an ALS-causing FUS mutant relative to wild-type human FUS. Injection of sonicated human FUS fibrils does not induce FUS aggregation and subsequent spreading after injection into naïve mouse brains containing only mouse FUS, indicating a species barrier to human FUS aggregation and its prion-like spread. Fibril-induced human FUS aggregates recapitulate pathological features of FTLD including increased detergent insolubility of FUS and TAF15 and amyloid-like, cytoplasmic deposits of FUS that accumulate ubiquitin and p62, but not TDP-43. Finally, injection of sonicated FUS fibrils is shown to exacerbate age-dependent cognitive and behavioral deficits from mutant human FUS expression. Thus, focal seeded aggregation of FUS and further propagation through prion-like spread elicits FUS-proteinopathy and FTLD-like disease progression.

TRIM25 predominately associates with anti-viral stress granules.

Stress granules (SGs) are induced by various environmental stressors, resulting in their compositional and functional heterogeneity. SGs play a crucial role in the antiviral process, owing to their potent translational repressive effects and ability to trigger signal transduction; however, it is poorly understood how these antiviral SGs differ from SGs induced by other environmental stressors. Here we identify that TRIM25, a known driver of the ubiquitination-dependent antiviral innate immune response, is a potent and critical marker of the antiviral SGs. TRIM25 undergoes liquid-liquid phase separation (LLPS) and co-condenses with the SG core protein G3BP1 in a dsRNA-dependent manner. The co-condensation of TRIM25 and G3BP1 results in a significant enhancement of TRIM25's ubiquitination activity towards multiple antiviral proteins, which are mainly located in SGs. This co-condensation is critical in activating the RIG-I signaling pathway, thus restraining RNA virus infection. Our studies provide a conceptual framework for better understanding the heterogeneity of stress granule components and their response to distinct environmental stressors.

The effectiveness of brief reminiscence-based psychosocial interventions for cancer patients: A systematic review and meta-analysis.

AIM: To determine the effectiveness of brief reminiscence-based psychosocial interventions in alleviating psychological distress in cancer patients. BACKGROUND: Cancer patients suffer tremendous psycho-spiritual pain, which affects their quality of life. Brief reminiscence-based psychosocial interventions have demonstrated positive effects on the mental health of cancer patients; however, the efficacy of these interventions has been inconsistent. DESIGN: A systematic review and meta-analysis. METHODS: This review was conducted and reported in accordance with the PRISMA 2020 checklist provided by the EQUATOR network. The Cochrane Library, Web of Science, PsycINFO, PubMed, Embase, CINAHL and Scopus databases were systematically searched from inception to 27 November 2022 to identify randomised controlled trials (RCTs) published in English. RESULTS: Twenty studies involving 1744 cancer participants were included. The meta-analysis showed statistically significant effects of brief reminiscence-based psychosocial interventions on hope, anxiety and depression at post-intervention. A separate analysis revealed that brief reminiscence-based psychosocial interventions had a sustainable effect on hope, spiritual well-being, anxiety and depression at 1 month after the intervention. However, no statistically significant effect on quality of life was found in our study either immediately after the intervention or at 1 month. CONCLUSIONS: Brief reminiscence-based psychosocial interventions can significantly reduce anxiety and depressive symptoms and improve hope and spiritual well-being in cancer patients. RELEVANCE TO CLINICAL PRACTICE: This study further supports that brief reminiscence-based psychosocial interventions should be incorporated into the routine care of cancer patients to address their psychosocial distress. PATIENT OR PUBLIC CONTRIBUTION: All authors of this article contributed to the study conception and design. All authors of the included studies provided original data for this paper.

A phage nucleus-associated RNA-binding protein is required for jumbo phage infection.

Large-genome bacteriophages (jumbo phages) of the proposed family Chimalliviridae assemble a nucleus-like compartment bounded by a protein shell that protects the replicating phage genome from host-encoded restriction enzymes and DNA-targeting CRISPR-Cas nucleases. While the nuclear shell provides broad protection against host nucleases, it necessitates transport of mRNA out of the nucleus-like compartment for translation by host ribosomes, and transport of specific proteins into the nucleus-like compartment to support DNA replication and mRNA transcription. Here, we identify a conserved phage nuclear shell-associated protein that we term Chimallin C (ChmC), which adopts a nucleic acid-binding fold, binds RNA with high affinity in vitro, and binds phage mRNAs in infected cells. ChmC also forms phase-separated condensates with RNA in vitro. Targeted knockdown of ChmC using mRNA-targeting dCas13d results in accumulation of phage-encoded mRNAs in the phage nucleus, reduces phage protein production, and compromises virion assembly. Taken together, our data show that the conserved ChmC protein plays crucial roles in the viral life cycle, potentially by facilitating phage mRNA translocation through the nuclear shell to promote protein production and virion development.

Psoas muscle index and psoas muscle density are associated with functional status in patients with degenerative lumbar spinal stenosis.

BACKGROUND: The factors affecting lumbar spinal function in patients with degenerative lumbar spinal stenosis (DLSS) are still unclear. OBJECTIVE: This study explored psoas major muscle morphology in patients with DLSS and its association with their functional status. METHODS: A retrospective study was conducted on 288 patients with DLSS and 260 control subjects. Psoas major muscle evaluation included three morphometric parameters at the L3/4 disc level: psoas major index (PMI), muscle attenuation, and psoas major morphological changes (MPM). The association between psoas major morphology and functional status was assessed using the Oswestry disability index (ODI). RESULTS: Both female and male patients with DLSS had a higher PMI and lower muscle attenuation. PMI and muscle attenuation were inversely correlated with age in the DLSS group. After multivariable analyses, the PMI and psoas major muscle attenuation were positively correlated with patients' functional status. CONCLUSION: The PMI and muscle attenuation were positively correlated with functional status in patients with DLSS. These findings have important implications for physiotherapy programs of postoperative rehabilitation and conservative management of DLSS.

Development and external validation of a predictive model for prolonged length of hospital stay in elderly patients undergoing lumbar fusion surgery: comparison of three predictive models.

PURPOSE: This study aimed to develop a predictive model for prolonged length of hospital stay (pLOS) in elderly patients undergoing lumbar fusion surgery, utilizing multivariate logistic regression, single classification and regression tree (hereafter, "classification tree") and random forest machine-learning algorithms. METHODS: This study was a retrospective review of a prospective Geriatric Lumbar Disease Database. The primary outcome measure was pLOS, which was defined as the LOS greater than the 75th percentile. All patients were grouped as pLOS group and non-pLOS. Three models (including logistic regression, single-classification tree and random forest algorithms) for predicting pLOS were developed using training dataset and internal validation using testing dataset. Finally, online tool based on our model was developed to assess its validity in the clinical setting (external validation). RESULTS: The development set included 1025 patients (mean [SD] age, 72.8 [5.6] years; 632 [61.7%] female), and the external validation set included 175 patients (73.2 [5.9] years; 97[55.4%] female). Multivariate logistic analyses revealed that older age (odds ratio [OR] 1.06, p < 0.001), higher BMI (OR 1.08, p = 0.002), number of fused segments (OR 1.41, p < 0.001), longer operative time (OR 1.02, p < 0.001), and diabetes (OR 1.05, p = 0.046) were independent risk factors for pLOS in elderly patients undergoing lumbar fusion surgery. The single-classification tree revealed that operative time ≥ 232 min, delayed ambulation, and BMI ≥ 30 kg/m2 as particularly influential predictors for pLOS. A random forest model was developed using the remaining 14 variables. Intraoperative EBL, operative time, delayed ambulation, age, number of fused segments, BMI, and RBC count were the most significant variables in the final model. The predictive ability of our three models was comparable, with no significant differences in AUC (0.73 vs. 0.71 vs. 0.70, respectively). The logistic regression model had a higher net benefit for clinical intervention than the other models. The nomogram was developed, and the C-index of external validation for PLOS was 0.69 (95% CI, 0.65-0.76). CONCLUSION: This investigation produced three predictive models for pLOS in elderly patients undergoing lumbar fusion surgery. The predictive ability of our three models was comparable. Logistic regression model had a higher net benefit for clinical intervention than the other models. Our predictive model could inform physicians about elderly patients with a high risk of pLOS after surgery.

A phage nucleus-associated RNA-binding protein is required for jumbo phage infection.

Large-genome bacteriophages (jumbo phages) of the Chimalliviridae family assemble a nucleus-like compartment bounded by a protein shell that protects the replicating phage genome from host-encoded restriction enzymes and CRISPR/Cas nucleases. While the nuclear shell provides broad protection against host nucleases, it necessitates transport of mRNA out of the nucleus-like compartment for translation by host ribosomes, and transport of specific proteins into the nucleus-like compartment to support DNA replication and mRNA transcription. Here we identify a conserved phage nuclear shell-associated protein that we term Chimallin C (ChmC), which adopts a nucleic acid-binding fold, binds RNA with high affinity in vitro, and binds phage mRNAs in infected cells. ChmC also forms phase-separated condensates with RNA in vitro. Targeted knockdown of ChmC using mRNA-targeting dCas13d halts infections at an early stage. Taken together, our data suggest that the conserved ChmC protein acts as a chaperone for phage mRNAs, potentially stabilizing these mRNAs and driving their translocation through the nuclear shell to promote translation and infection progression.

Enhanced Recovery After Surgery (ERAS) Program for Anterior Cervical Discectomy and Fusion (ACDF) in Patients Over 60 Years Old.

Background: Enhanced recovery after surgery (ERAS) is currently widely used in many surgical specialties, but there is still a lack of concern about the cervical ERAS program for old patients (>60 years old). We aimed to determine whether our ERAS program significantly improved satisfaction and outcomes in old patients (>60 years old) with anterior cervical discectomy and fusion (ACDF). Methods: This is a retrospective cohort study. The study enrolled patients if they were over the age of 60 years old underwent ACDF from July 2019 and June 2021 (ERAS group) and from January 2018 and June 2019 (non-ERAS group). Data including demographic, comorbidity, and surgical information were collected. We also evaluated ERAS process compliance, primary outcome, surgical complication, and length of stay (LOS). Results: There were 135 patients in the ERAS group, and 122 patients in the non-ERAS group were included. A comparison of the demographic data revealed that there were no statistically significant intergroup differences observed between the group. Overall, ERAS pathway compliance was 91.9%. There were no significant differences in the fusion levels, operative time, intraoperative blood loss, postoperative VAS score, and complications between the ERAS and non-ERAS groups. In addition, there was no significant difference in readmission and mortality at 30-day follow-up between the two groups. However, we observed a statistically significant decrease in the LOS in the ERAS group (8.68±2.34 of ERAS group versus 10.43±4.05 in non-ERAS group, p=0.013). Conclusion: This report describes the first ERAS protocol used in old patients with ACDF. Our ERAS program is safe and associated with incremental benefits with respect to LOS in old patients with ACDF.

FAM91A1-TBC1D23 complex structure reveals human genetic variations susceptible for PCH.

Pontocerebellar hypoplasia (PCH) is a group of rare neurodevelopmental disorders with limited diagnostic and therapeutic options. Mutations in WDR11, a subunit of the FAM91A1 complex, have been found in patients with PCH-like symptoms; however, definitive evidence that the mutations are causal is still lacking. Here, we show that depletion of FAM91A1 results in developmental defects in zebrafish similar to that of TBC1D23, an established PCH gene. FAM91A1 and TBC1D23 directly interact with each other and cooperate to regulate endosome-to-Golgi trafficking of KIAA0319L, a protein known to regulate axonal growth. Crystal structure of the FAM91A1-TBC1D23 complex reveals that TBC1D23 binds to a conserved surface on FAM91A1 by assuming a Z-shaped conformation. More importantly, the interaction between FAM91A1 and TBC1D23 can be used to predict the risk of certain TBC1D23-associated mutations to PCH. Collectively, our study provides a molecular basis for the interaction between TBC1D23 and FAM91A1 and suggests that disrupted endosomal trafficking underlies multiple PCH subtypes.

Comparative efficacy of various exercise interventions on depression in older adults with mild cognitive impairment: A systematic review and network meta-analysis.

BACKGROUND: Exercise is a promising nonpharmacological treatment for improving depression in older adults with MCI, but it is unclear which exercises are most effective. The objectives of this study were to compare and rank the effectiveness of various exercise interventions for depression in mild cognitive impairment (MCI) and to investigate the effects of exercise on depression. METHODS: The PRISMA-NMA guidelines were applied to the development and reporting of review criteria. The Cochrane Library, Web of Science, PsycINFO, PubMed, EMBASE, CINAHL, and Scopus databases were systematically searched by combining search terms for randomized controlled trial studies (RCTs) published in English from individual databases with the earliest available date set to March 10, 2023. Two evaluators independently selected and evaluated eligible studies of changes in depression in older adults with MCI after an exercise intervention. A protocol for this systematic review was registered in PROSPERO (Registration number: CRD42022377052). RESULTS: A network meta-analysis was conducted on 15 eligible RCTs consisting of 4271 subjects, including aerobic (n = 6), mind-body (n = 6) and multicomponent (n = 3) exercise trials. Compared to controls, mind-body exercise showed the strongest improvement in depressive symptoms (SMD = -0.63, 95% CI: -1.13, -0.14), followed by aerobic (SMD = -0.57, 95% CI: -0.88, -0.26) and multicomponent exercise (SMD = -0.53, 95% CI: -1.02, -0.03). Notably, there were no statistically significant differences between exercise types: aerobic vs. mind-body (SMD = 0.06, 95% PrI: -0.71, 0.84), multicomponent vs. mind-body (SMD = 0.11, 95% PrI: -0.75, 0.97), or multicomponent vs. aerobic (SMD = 0.04, 95% PrI: -0.771, 0.86). CONCLUSIONS: In this review, we found that mind-body exercise was most effective when compared to conventional controls and that multiple exercise modalities (aerobic, mind-body, and multicomponent exercise) had beneficial and comparable effects in reducing depressive states in older adults with MCI. These findings may guide clinical geriatric stakeholders and allied health professionals in providing more scientifically optimal exercise prescriptions for older adults with MCI. In the future, more high-quality, long-term clinical trials are needed to support the exploration of longer-term dynamic effects.

Bibliometric analysis of research on neurodegenerative diseases and single-cell RNA sequencing: Opportunities and challenges.

Neurodegeneration, characterized by the progressive deterioration in neuronal structure or function, presents an elusive mechanism. The use of single-cell RNA sequencing (scRNA-seq) technology in the clinic is becoming increasingly prevalent in recent decades. This technology offers unparalleled cell-level insights into neurodegenerative diseases, establishing itself as a potent tool for elucidating these diseases underlying mechanisms. Here, we made a deep investigation for scRNA-seq research in neurodegenerative diseases using bibliometric analysis from 2009 to 2022. We observed a robust upward trajectory in the number of publications on this subject. The United States stood out as the principal contributor to this expanding field. Specifically, the University of California System exhibited notable research prowess in this field. Alzheimer disease and Parkinson disease were the diseases most frequently investigated. Key research hotspots include the creation of a molecular brain atlas and identification of vulnerable neuronal subpopulations and potential therapeutic targets at the transcriptomic level.

CrMP-Sol database: classification, bioinformatic analyses and comparison of cancer-related membrane proteins and their water-soluble variant designs.

Membrane proteins are critical mediators for tumor progression and present enormous therapeutic potentials. Although gene profiling can identify their cancer-specific signatures, systematic correlations between protein functions and tumor-related mechanisms are still unclear. We present here the CrMP-Sol database ( https://bio-gateway.aigene.org.cn/g/CrMP ), which aims to breach the gap between the two. Machine learning was used to extract key functional descriptions for protein visualization in the 3D-space, where spatial distributions provide function-based predictive connections between proteins and cancer types. CrMP-Sol also presents QTY-enabled water-soluble designs to facilitate native membrane protein studies despite natural hydrophobicity. Five examples with varying transmembrane helices in different categories were used to demonstrate the feasibility. Native and redesigned proteins exhibited highly similar characteristics, predicted structures and binding pockets, and slightly different docking poses against known ligands, although task-specific designs are still required for proteins more susceptible to internal hydrogen bond formations. The database can accelerate therapeutic developments and biotechnological applications of cancer-related membrane proteins.

Establishment of environment-sensitive probes targeting BRD3/BRD4 for imaging and therapy of tumor.

The BET (bromo and extra-terminal) family proteins are epigenetic readers and master transcription coactivators, which have attracted great interests as cancer therapeutic targets. However, there are few developed labeling toolkits that can be applied for the dynamic studies of BET family proteins in living cells and tissue slices. In order to label and study the distribution of the BET family proteins in tumor cells and tumor tissues, a novel series of environment-sensitive fluorescent probes (6a-6c) were designed and evaluated for their labeling properties. Interestingly, 6a is capable of identifying tumor tissue slices and making a distinction between the tumor and normal tissues. Moreover, it can localize to the nuclear bodies in tumor slices just like BRD3 antibody. In addition, it also played an anti-tumor role through the induction of apoptosis. All these features render 6a may compatible for immunofluorescent studies and future cancer diagnosis, and guide for the discovery of new anticancer drugs.

The association between low virulence organisms in different locations and intervertebral disc structural failure: A meta-analysis and systematic review.

Many factors may trigger intervertebral disc (IVD) structural failure (intervertebral disc degeneration (IDD) and endplate changes), including inflammation, infection, dysbiosis, and the downstream effects of chemical factors. Of these, microbial diversity in the IVD and elsewhere in the body has been considered as one of the potential reasons for disc structural failure. The exact relationships between microbial colonization and IVD structural failure are not well understood. This meta-analysis aimed to investigate the impact of microbial colonization and its location (such as skin, IVD, muscle, soft tissues, and blood) on IVD structural failure and corresponding low back pain (LBP) if any. We searched four online databases for potential studies. The potential relationships between microbial colonization in different sample sources (such as skin, IVD, muscle, soft tissues, and blood) and IDD and endplate change were considered as primary outcomes. Odds ratio (OR) and 95% confidence intervals (CI) for direct comparisons were reported. Grading of Recommendations Assessment, Development and Evaluation (GRADE) scale was used to assess the quality of evidence. Twenty-five cohort studies met the selection criteria. Overall pooled prevalence of microbial colonization in 2419 patients with LBP was 33.2% (23.6%-43.6%). The pooled prevalence of microbial colonization in 2901 samples was 29.6% (21.0%-38.9%). Compared with the patients without endplate change, the patients with endplate changes had higher rates of microbial colonization of disc (OR = 2.83; 95% CI = 1.93-4.14; I 2 = 37.6%; p = 0.108). The primary pathogen was Cutibacterium acnes which was present in 22.2% of cases (95% CI = 13.3%-32.5%; I 2 = 96.6%; p = 0.000). This meta-analysis and systematic review found low-quality grade evidence for an association between microbial colonization of disc with endplate changes. The primary pathogen was C. acnes. Due to lack of enough high-quality studies and methodological limitations of this review, further studies are required to improve our understanding of the potential relationships and mechanisms of microbiota, dysbiosis, IVD colonization and IVD structural failure.