Phase I Study of Intravitreal Injection of Autologous CD34+ Stem Cells from Bone Marrow in Eyes with Vision Loss from Retinitis Pigmentosa.

Purpose: To evaluate the feasibility and safety of intravitreal injection of autologous CD34+ stem cells from bone marrow (BMSCs) in eyes with vision loss from retinitis pigmentosa (RP). Design: Phase I prospective, open-label, single-center study. Participants: Seven eyes (7 patients) with RP with best-corrected visual acuity (BCVA) of 20/60 to 20/400 or visual field constriction to within 10°. Methods: A comprehensive examination with ETDRS BCVA, macular OCT, perimetry, and fluorescein angiography was performed at baseline, 1 to 3 months, and 6 months after study treatment. Bone marrow aspiration, isolation of CD34+ BMSCs under good manufacturing practice conditions, and intravitreal cell injection were performed on the same day. The CD34+ cells were isolated from bone marrow using a Ficoll gradient and the Miltenyi CliniMACS system. Isolated CD34+ cells were released for clinical use if viability, sterility, and purity met the release criteria accepted by the United States Food and Drug Administration for this clinical study. Main Outcome Measures: Number of CD34+ cells isolated for injection and adverse events associated with study treatment during follow-up. Secondary outcome measures are changes in BCVA and perimetry. Results: All isolated CD34+ cells passed the release criteria. A mean of 3.26 ± 0.66 million viable CD34+ cells (range 1.6 to 7.05 million) were injected intravitreally per eye. No adverse event was noted during the study follow-up except for 1 participant who was noted with transient cells in the anterior chamber with mild elevation in intraocular pressure at 18 hours after study injection which normalized by 24 hours. Best-corrected visual acuity remained within 2 lines of baseline or improved in all participants at 6 months follow-up. Perimetry was stable or improved in all eyes during study follow-up except 1 eye with transient improvement at 1 month and worsening of both eyes at 6 months. Conclusions: Intravitreal injection of autologous CD34+ BMSCs is feasible and appears to be well tolerated in eyes with vision loss from RP. A larger randomized prospective study would be needed to evaluate further the safety and potential efficacy of this cell therapy for vision loss associated with RP. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Mitochondrial 'Birth-Death' coordinator: An intelligent hydrogen nanogenerator to enhance intervertebral disc regeneration.

Currently, mitochondrial dysfunction caused by oxidative stress is a growing concern in degenerative diseases, notably intervertebral disc degeneration (IVDD). Dysregulation of the balance of mitochondrial quality control (MQC) has been considered the key contributor, while it's still challenging to effectively harmonize different MQC components in a simple and biologically safe way. Hydrogen gas (H2) is a promising mitochondrial therapeutic molecule due to its bio-reductivity and diffusibility across cellular membranes, yet its relationship with MQC regulation remains unknown. Herein, we propose a mitochondrial 'Birth-Death' coordinator achieved by an intelligent hydrogen nanogenerator (Fe@HP-OD), which can sustainably release H2 in response to the unique microenvironment in degenerated IVDs. Both in vitro and in vivo results prove alleviation of cellular oxidative stress and restoration of nucleus pulposus cells function, thereby facilitating successful IVD regeneration. Significantly, this study for the first time proposes the mitochondrial 'Birth-Death' coordination mechanism: 1) attenuation of overactivated mitochondrial 'Death' process (UPRmt and unselective mitophagy); and 2) activation of Adenosine 5'-monophosphate-activated protein kinase (AMPK) signaling pathway for mitochondrial 'Birth-Death' balance (mitochondrial biogenesis and controlled mitophagy). These pioneering findings can fill in the gaps in molecular mechanisms for H2 regulation on MQC homeostasis, and pave the way for future strategies towards restoring equilibrium of MQC system against degenerative diseases.

Effect of Different Injury Morphology of the Endplate on Intervertebral Disc Degeneration: Retrospective Cohort Study.

OBJECTIVES: To describe a simplified classification scheme for endplate injury morphology based on 3D CT and to examine possible associations between endplate injury morphology and vertebral space and other variables such as type of fracture and disc degeneration in a group of patients with thoracolumbar fractures. METHODS: This study was a retrospective cohort study. We collected patients with thoracolumbar fractures admitted from January 2015 to August 2020 and divided them into three groups based on the morphology of endplate injury (45 cases of mild endplate injury, 54 cases of moderate endplate injury, and 42 cases of severe endplate injury, SEI). Data of vertebral body and intervertebral space height and angle, the Pfirrmann grade, endplate healing morphology were collected during preoperative, postoperative, and long-term follow-up of patients in each group. One-way analysis of variance (ANOVA), chi-squared test, and repeated measurement ANOVA were used to compare and analyze the influence of endplate injury morphology on patient prognosis. RESULTS: Most moderate injuries to the endplate (fissure-type injury) and severe injuries (irregular depression-type injury, Schmorl's node-type injury) resulted in significant disc degeneration in the long-term transition. This study also showed significant differences in the height of the anterior margin of the injured spine and the intervertebral space height index during this process. CONCLUSIONS: The current study suggests that although the region of injury in endplate fissure-type injury is small preoperatively, it may be a major factor in leading to severe disc degeneration, loss of intervertebral height, and Cobb angle in the long term. The results of our study therefore may allow surgeons to predict the prognosis of patients with thoracolumbar fractures and guide their treatment.

Intravitreal faricimab for treatment naïve patients with neovascular age-related macular degeneration: a real-world prospective study.

BACKGROUND: Intravitreal faricimab, a bispecific antibody targeting both angiopoietin-2 (Ang-2) and vascular endothelial growth factor-A (VEGF-A), was recently introduced for the treatment of neovascular age-related macular degeneration (nAMD), diabetic macular oedema and cystoid macular oedema secondary to retinal vein occlusion. The aim of our study was to assess the efficacy, safety and durability of intravitreal faricimab in a real-world cohort of treatment-naïve patients with nAMD. METHODS: Single-centre, prospective cohort study of 21 eyes from 19 treatment-naïve nAMD patients who were treated with intravitreal faricimab from October 2022 to April 2024. Patients underwent a loading dose (LD) of 4 monthly faricimab injections followed by a treat-and-extend regimen. Primary outcomes included best-corrected visual acuity (BCVA) and structural parameters from spectral-domain optical coherence tomography (SD-OCT). Secondary outcomes included the proportion of eyes achieving a dry macula, maximal fluid-free interval and intended interval at last follow-up. RESULTS: The study included 21 eyes of 19 patients (mean age 83.1 years). After LD, 93.3% of eyes achieved a dry macular SD-OCT scan within a median time of 8 weeks. At the first extension, 53% of eyes remained dry, while 47% showed fluid recurrence. Long-term analysis (n = 14) revealed significant reductions in macular volume (MV), central subfield thickness (CST), and pigment epithelial detachment (PED) height over a median follow-up of 64.9 weeks, with sustained visual and anatomical improvements. Median BCVA, CST, and MV at the final follow-up were significantly improved from baseline (p < 0.01). The intended interval between injections was ≥ 12 weeks in 42.86% of eyes. No cases of intraocular inflammation were observed, although 10% experienced retinal pigment epithelial tears. CONCLUSIONS: Intravitreal faricimab demonstrated favourable efficacy, safety, and durability outcomes in a real-world cohort of treatment-naïve nAMD patients.

Increased vascular endothelial growth factor expression is associated with cruciate ligament degeneration in patients with osteoarthritis of the knee.

BACKGROUND: This study aimed to investigate the expression of vascular endothelial growth factor (VEGF) in cruciate ligaments from patients with osteoarthritis (OA). It was hypothesized that the expression level of VEGF is associated with the extent of degeneration of the cruciate ligaments. METHODS: Remnants of anterior cruciate ligaments (ACLs) from patients with acute ACL injury due to trauma, and ACLs and posterior cruciate ligaments (PCLs) from patients with primary OA were assessed histologically. Samples were immunohistochemically stained with VEGF and tenomodulin, and immunopositive cells were quantitatively assessed by the histological grades of ligament degeneration. RESULTS: Histological analysis showed significant degeneration of the ACLs from OA patients compared with trauma patients, with increased expression of VEGF correlating with higher grades of degeneration. Conversely, tenomodulin expression was lower in more degenerated cruciate ligaments. The percentage of VEGF-positive cells was correlated inversely with that of tenomodulin-positive cells. CONCLUSIONS: Increased VEGF expression is associated with degeneration of cruciate ligaments in patients with osteoarthritis of the knee.

Correlation of the single-segment dynamic stabilization with different segmental mobility and zygapophysial (facet) joint degeneration: a retrospective study in northern China.

OBJECTIVE: To compare the clinical and radiographic outcomes of single-segment posterior decompression combined with two different non-fusion dynamic stabilization systems, Isobar EVO and Isobar TTL, in the context of facet joint degeneration and segmental mobility. METHOD: A retrospective study was conducted on 47 patients who underwent single-segment surgery at the L4/5 level using either the Isobar EVO (n = 23) or Isobar TTL (n = 24) systems. We assessed facet joint degeneration on both sides of the fixed (L3/4, L4/5) and superior adjacent (L2/3) segments using the Fujiwara MRI grading system. Clinical outcomes were evaluated using the Oswestry Disability Index (ODI) and visual analog scale (VAS) for back and leg pain at baseline, 12 months, and 24 months postoperatively. RESULT: Both groups exhibited significant facet joint degeneration at the fixed segments (L3/4 and L4/5) at 24 months. The TTL group also showed significant degeneration at the superior adjacent segment (L2/3), whereas the EVO group did not. Restoration of lumbar lordosis was significantly better in the EVO group. Pain and disability scores improved more in the EVO group than in the TTL group at both 12 and 24 months postoperatively. CONCLUSION: The Isobar EVO system, with its enhanced mobility, may delay facet joint degeneration in the superior adjacent segment compared to the Isobar TTL system. However, both systems result in degeneration at the fixed segment, indicating a need for further improvements to mimic the natural biomechanics of the spine more closely.

Untargeted Metabolomic Study of Patients with Wet Age-Related Macular Degeneration in Aqueous Humor.

Purpose: The objective of this study was to ascertain metabolic biomarkers and investigate the metabolic alterations associated with aqueous humor (AH) in wet age-related macular degeneration (AMD). Methods: AH samples were collected from a total of 20 participants, including 10 individuals diagnosed with wet AMD and 10 individuals undergoing cataract surgery, serving as the control group. Metabolomics analysis was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify and quantify metabolites. Results: A total of 155 metabolites were identified in the AH samples. Among them, 10 metabolites emerged as potential biomarkers capable of differentiating patients with wet AMD from the control group. In the AH of wet AMD patients, there was increased expression of Cardiolipin (CL) (72:5), Diglyceride (DG) (18:3_18:2), DG (36:5e) and Triglyceride (TG) (24:7), while the expression of Ceramides (Cer) (d32:0), Cer (d34:0), Cer (d36:0), Monogalactosyldiacylglycerol (MGDG) (16:1_18:3), Sphingosine (SPH) (d18:0) and TG (16:0_10:4_16:0) was down regulated. Conclusion: Through metabolomics analysis of AH, this study successfully uncovered valuable metabolic biomarkers linked to wet AMD. These findings contribute to a more comprehensive understanding of the pathogenesis of wet AMD and offer potential avenues for the development of innovative treatment strategies for this condition.

Protein overexpression by adeno-associated virus-based gene therapy products in cardiomyocytes induces endoplasmic reticulum stress and myocardial degeneration in mice.

Gene therapy (GT) products created using adeno-associated virus (AAV) vectors tend to exhibit toxicity via immune reactions, but other mechanisms of toxicity remain incompletely understood. We examined the cardiotoxicity of an overexpressed transgenic protein. Male C57BL/6J mice were treated with a single intravenous dose of product X, an AAV-based GT product, at 2.6 × 1013 vg/kg. Necropsies were performed at 24 h, 7 days, and 14 days after dosing. Pathological examination and gene expression analysis were performed on the heart. Histopathologically, hypertrophy and vacuolar degeneration of cardiomyocytes and fibrosis were observed 14 days after dosing. Immunohistochemistry for endoplasmic reticulum (ER) stress-related proteins revealed increased positive reactions for glucose-regulated protein 78 and C/EBPR homologous protein in cardiomyocytes 7 days after dosing, without histopathological abnormalities. Fourteen days after dosing, some cardiomyocytes showed positivity for PKR-like endoplasmic reticulum kinase and activating transcription factor 4 expression. Ultrastructurally, increases in the ER and cytosol were observed in cardiomyocytes 7 days after dosing, along with an increase in the number of Golgi apparatus compartments 14 days after dosing. The tissue concentration of the transgene product protein increased 7 days after dosing. Gene expression analysis showed upregulation of ER stress-related genes 7 days after dosing, suggesting activation of the PKR-like ER kinase pathway of the unfolded protein reaction (UPR). Thus, the cardiotoxicity induced by product X was considered to involve cell damage caused by the overexpression of the product protein accompanied by UPR. Marked UPR activation may also cause toxicity of AAV-based GT products.

Clinical and Biochemical Analysis of Glutamate-Cysteine Ligase Deficiency Presented with Late-Onset Spinocerebellar Ataxia and Hemolytic Anemia.

Introduction: Glutamate-cysteine ligase catalytic subunit (GCLC), previously known as gamma-glutamyl-cysteine synthetase, is an essential rate-limiting step in glutathione synthesis. Glutathione modulates multitudes of critical cellular processes and scavenges free radicals. Its deficiency is reported to cause hemolysis of variable severity and is a rare cause of neurological abnormalities such as spinocerebellar ataxia. Clinical Presentation: We report a 55-year-old female patient with progressive late-onset ataxia, lower limb spasticity, and chronic hemolytic anemia found to have a GCLC pathogenic variant and low glutathione level. Magnetic resonance imaging of the head and cervical spine showed global cerebellar atrophy with widened folia and decreased diameter of the upper cervical spine. Blood workup revealed hemolytic anemia with genetic testing confirmed a homozygous variant, c.514 T>A in exon 4 of the GCLC gene, resulting in Ser172Thr (TCC>ACC). Management encompassed a multidisciplinary approach with a trial of high-dose alpha-lipoic acid, glutathione supplement, and physical therapy. Conclusions: GCLC deficiency manifesting with hemolysis has been reported in 12 cases worldwide from 6 independent families, with only 4 cases having additional neurological manifestations. To date, no specific GCLC gene mutation has been attributed to the reported neurological constellation of symptoms. To the best of our knowledge, this is the first case report of late-onset spinocerebellar degeneration as a manifestation of c.514T>A (p. S172T) GCLC pathological variant genetic mutation.

Stage III xanthogranulomatous pyelonephritis with sarcomatoid degeneration.

Xanthogranulomatous pyelonephritis (XGP) is an uncommon chronic condition characterized by destructive granulomatous disease of the kidney with uncertain etiology. Significant risk factors for XGP are represented by the coexistence of history of nephrolithiasis, diabetes mellitus, recurrent urinary tract infections and other immunocompromised conditions. It is also associated with higher risk of malignancy, reported in up to 11% of patients. We report a case of a 76-year-old female who presented to the emergency department with an insidious onset of abdominal and right lower back pain. She had a history of renal stones and diabetes mellitus. On physical examination, a painful fistulous orifice in skin on the right lumbar region was found. CT images showed a nonfunctioning right kidney replaced by multiple necrotic cavities with inflammatory involvement of the right hepatic lobe and a nephron-cutaneous fistula. These CT findings were strongly suggestive of XGP (III state). CT images obtained before and after the administration of intravenous contrast material showed also a hyper-vascularized renal mass with irregularly thickened walls confirmed by a targeted CEUS examination and suspicious for malignancy. Pathologic examination confirmed the chronic pyelonephritis and revealed evidence of a concomitant sarcomatoid lesion. This case underlines the central role of a multimodality imaging approach in the emergency department and how this affects the correct management and treatment of patients. In fact, MDCT is considered the current gold standard for the diagnosis and the staging of XPG but the contrast-enhanced ultrasound (CEUS) in selected patients can increase the diagnostic accuracy in the uncertain small renal masses detected on CT scans.

YTHDF1-regulated ALOX5 in retinal pigment epithelial cells under hypoxia enhances VEGF expression and promotes viability, migration, and angiogenesis of vascular endothelial cells.

Upregulation of vascular endothelial growth factor (VEGF) and enhanced angiogenesis have been implicated in the severe progression of age-related macular degeneration (AMD). Abnormal arachidonate 5-lipoxygenase (ALOX5) is associated with AMD pathogenesis. However, no reports have shown the causal role of ALOX5 in angiogenesis during AMD. In the present study, ARPE-19 cells were exposed to hypoxia, an inducer of VEGF expression. Potential proteins implicated in AMD progression were predicted using bioinformatics. RNA affinity antisense purification-mass spectrometry (RAP-MS) was applied to identify the binding proteins of ALOX5 3'UTR. Expression of ALOX5 and YTH N6-methyladenosine RNA-binding protein 1 (YTHDF1) was detected by qRT-PCR and western blotting. VEGF expression and secretion were assessed by immunofluorescence and ELISA, respectively. The chicken embryo chorioallantoic membrane (CAM) was used to analyze the effect of ALOX5 on angiogenesis. RNA stability was assayed using the Actinomycin D assay. The results show that hypoxia promoted cell growth and increased VEGF expression in ARPE-19 cells. ALOX5 was associated with AMD progression, and hypoxia upregulated ALOX5 expression in ARPE-19 cells. ALOX5 silencing reduced VEGF expression induced by hypoxia in ARPE-19 cells. Moreover, the conditioned medium of ALOX5-silenced ARPE-19 cells could suppress the viability and migration of HUVECs and diminish angiogenesis in the CAM. Furthermore, YTHDF1 was validated to bind to ALOX5 3'UTR, and YTHDF1 promoted ALOX5 expression by elevating the stability of ALOX5 mRNA. In conclusion, our findings demonstrate that YTHDF1-regulated ALOX5 increases VEGF expression in hypoxia-exposed ARPE-19 cells and enhances the viability, migration, and angiogenesis of vascular endothelial cells.

Incidence of Anxiety and Depression in Adult Patients with Chronic Discogenic Back Pain.

BACKGROUND: To analyze the results of domestic and foreign studies of the comorbidity of anxiety-depressive disorders and discogenic back pain in adult patients. SUBJECTS AND METHODS: An analysis of Russian-language and foreign literature was carried out with a search depth of 5 years (2019-2024) in the following databases: PubMed, Springer, Wiley Online Library, Taylor & Francis Online, US National Library of Medicine National Institutes of Health, ScienceDirect and e-Library. RESULTS: Numerous studies have shown that depression and anxiety influence treatment outcomes in intervertebral disc degeneration (IVDD). Ineffective pharmacotherapy and inappropriate surgical interventions for depression and anxiety may significantly negatively affect the outcomes reported by patients with IVDD and chronic discogenic back pain. In addition, depression and anxiety have been reported to be risk factors for complications, chronic pain, and readmission after spinal surgery. Symptoms associated with mental stress, including depression and anxiety, were shown to be associated with changes in skeletal muscle tension symmetry in patients with IVDD, indicating that mental state is associated with muscle function. Therefore, it is useful for neurologists and neurosurgeons to identify anxiety and depressive disorders in patients with IVDD in order to promptly prescribe appropriate therapy for them. CONCLUSION: Timely diagnosis of anxiety and depressive disorders and anxiety in patients with IVDD and chronic discogenic back pain requires an interdisciplinary approach with the participation of psychiatrists, neurologists and clinical pharmacologists, which is important for improving positive treatment outcomes and improving the quality of life of patients.

[Analysis of therapeutic effect of fibrocystic degeneration of vocal folds].

Objective:To explore the differences in clinical presentation and therapeutic outcomes between vocal fold fibrocystic degeneration and other common benign lesions, such as vocal fold polyp and cyst. Methods:Vocal function was assessed before and after surgery in 10 cases of vocal fold fibrocystoids, 30 cases of vocal fold polyps and 10 cases of vocal fold cysts at Department of Voice Medicine, Xiamen University Zhongshan Hospital. The voice Assessments included GRBAS（G-scale）, VHI-10 scale, Reflux Symptom Index（RSI） scale, stroboscope, acoustic objective analysis, and aerodynamics measurements. The acoustice analysis parameters included fundamental frequency（F0）, fundamental frequency perturbation（Jitter）, amplitude perturbation（Shimmer） and voice disturbance severity index（DSI）, while the maximum phonation time（MPT） was assessed for aerodynamics. Stroboscopic parameters included vocal fold straightness, vocal fold color, glottic closure and mucosal wave. All three groups underwent phonomicrosurgery and a follow-up review was conducted one month later. Pre-and post-operative function assessment parameters were compared across the three groups. Results:Significant differences were founded in the G grade, Jitter, Shimmer, DSI, glottic closure and mucosal wave between the vocal fold fibrocystic degeneration group and the vocal fold polyp and vocal fold cyst group（P<0.05）. Most voice function parameters in all three groups showed significant improvement after surgery（P<0.05）. The improvement of VHI（10）, RSI and mucosal wave scores in the vocal fold fibrocystic lesion group was significantly different from that of the vocal fold polyp group（P<0.05）. Conclusion:Vocal fold fibrocystic degeneration is a more severe than that of vocal fold polyps and cysts, which are two common benign vocal fold lesions. Phonomicrosurgery is an effective treatment for vocal fold fibrocystic degeneration, but its curative effect are less favorable compared to those for vocal fold polyps and vocal fold cysts. Therefore, a detailed preoperative evaluation is essential for predicting surgical outcomes.

Protein Kinase C and Matrix Metalloproteinases Expression Using Phorbol Myristate Acetate in Degenerative Intervertebral Disc Cells.

Background: Degeneration of nucleus pulposus (NP) cells involves multiple factors. The relationship between the canonical Wnt/ß-catenin signaling pathway and matrix metalloproteinases (MMPs) is important in cellular senescence. Protein kinase C (PKC), an intermediate of the non-canonical Wnt pathway stimulated by phorbol myristate acetate (PMA), possibly prevents NP cell senescence, although not yet demonstrated in human-based studies. This study aimed to investigate the effect of PMA stimulation on the non-canonical and canonical Wnt pathways and MMP expression in human NP cells to ascertain its inhibitory effects on the senescence of NP cells. Methods: Human disc tissues of Pfirrmann grades 1 and 2 were collected from patients during spinal surgery and subsequently cultured. Protein and ribonucleic acid (RNA) were isolated from NP cells treated with PMA (400 nM) for 24 hours. Expression of MMP1, MMP13, tissue inhibitor of matrix metalloproteinase 1 (TIMP1), a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5), transient receptor potential vanilloid 4 (TRPV4), interleukin-6 (IL-6), and ß-catenin were detected using western blot analysis. Messenger RNA (mRNA) expression of type II collagen and glycosaminoglycan (GAG) were analyzed using reverse transcription polymerase chain reaction. IL-6 and prostaglandin E2 (PGE2) levels were measured using enzyme-linked immunosorbent assay. Results: Expression of PKC-δ (intermediate of the non-canonical Wnt pathway) and ß-catenin (intermediate of the canonical Wnt pathway) was increased by PMA treatment. The mRNA levels of type II collagen and GAG increased; however, their protein levels were not altered. PMA treatment increased the expression of MMP1, TIMP1, ADAMTS5, IL-6, PGE2, and TRPV4; however, the expression of MMP13 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) was unaltered. Conclusions: PMA activated PKC-δ, affecting the non-canonical Wnt pathway; however, its effect on ß-catenin in the canonical Wnt pathway was limited. ß-catenin activation through the TRPV4 channel led to increased expression of MMP1 and ADAMTS5 and that of IL-6 and PGE2 owing to NF-κB expression. Consequently, the degeneration of NP cells was not prevented.

QSM-detected iron accumulation in the cerebellar gray matter is selectively associated with executive dysfunction in non-demented ALS patients.

Background: This study aimed to assess whether quantitative susceptibility imaging (QSM)-based measures of iron accumulation in the cerebellum predict cognitive and behavioral features in non-demented amyotrophic lateral sclerosis (ALS) patients. Methods: A total of ALS patients underwent 3-T MRI and a clinical assessment using the ALS Functional Rating Scale-Revised (ALSFRS-R) and the Edinburgh Cognitive and Behavioural ALS Screen (ECAS). Regression models were applied to each subscale of the cognitive section of the ECAS and the ECAS-Carer Interview to examine the effect of QSM-based measures in white and gray matter (WM; GM) of the cerebellum, separately for right, left, and bilateral cerebellar regions of interest (ROIs). These effects were compared to those of cerebellar volumetrics in WM/GM, right and left hemispheres while controlling for demographics, disease status, and total intracranial volume. Results: Higher QSM measures of the cerebellar GM on the left, right, and bilateral sides significantly predicted (ps ≤ 0.003) a greater number of errors on the executive functioning (EF) subscale of the ECAS (ECAS-EF). Moreover, higher GM-related, QSM measures of the cerebellum were associated with an increased probability of a below-cut-off performance on the ECAS-EF (ps ≤ 0.024). No significant effects were observed for QSM measures of the cerebellar WM or for volumetric measures on the ECAS-EF. Other ECAS measures showed no significant effects. Bilateral QSM measures of the cerebellar GM also selectively predicted performance on backward digit span and social cognition tasks. Discussion: Iron accumulation within the cerebellar GM, particularly in the cerebellar cortices, may be associated with executive functioning deficits in non-demented ALS patients. Therefore, QSM-based measures could be useful for identifying the neural correlates of extra-motor cognitive deficits in ALS patients.

The influence of proliferative tissue on Hounsfield unit and its correlation with BMD in middle-aged and elderly patients with lumbar degenerative diseases.

PURPOSE: The difference of Hounsfield Unit (HU) value in different regions of L3 vertebra in middle-aged and elderly patients with lumbar degeneration diseases (LDD) was analyzed. To investigate the influence of proliferative tissue on HU value of cancellous bone and its correlation with bone mineral density (BMD). METHODS: The medical records of middle-aged and elderly patients with LDD in our hospital from December 2020 to December 2023 were retrospectively analyzed. The patients were divided into osteophyte group and no-osteophyte group according to the presence or absence of osteophyte formation on lumbar spine X-ray. In osteophyte group, cancellous bone HU value, containing cortical bone overall HU value and containing osteophyte overall HU value in L3 vertebra were measured on the lumbar CT cross-section. In no-osteophyte group, only the cancellous bone HU value and the containing cortical bone overall HU value were measured. Differences in HU value in different regions of the L3 vertebral body were compared within and between groups of middle-aged and elderly patients with LDD, respectively. To investigate its effect on cancellous bone HU measurements and to do a correlation analysis with patients' BMD. RESULTS: A total of 115 patients with LDD were included in this study, including 65 males and 50 females, with an average age of 67.83 ± 6.59 years. The results of the study showed no statistical differences in age (P = 0.15), gender (P = 0.57), smoking (P = 0.88), drinking history (P = 0.76), medical history (P > 0.05) and BMI(P = 0.29) between the two groups. In osteophyte group, the mean cancellous bone HU value was 98.00 ± 25.50 HU, the containing cortical bone overall HU value was 189.02 ± 46.18 HU, and the containing osteophyte overall HU value was 232.69 ± 56.01 HU. The overall HU values containing cortical bone and containing osteophyte were significantly higher than cancellous bone HU value (P < 0.001). In no-osteophyte group, the mean cancellous bone HU value was 102.04 ± 19.64 HU, and the containing cortical bone overall HU value was 175.00 ± 28.97 HU, which was statistically significantly different (P < 0.001). There was no significant difference in cancellous bone HU value and the containing cortical bone overall HU value between the two groups (P > 0.05). The results of the Pearson correlation analysis showed a significant correlation between the cancellous bone HU value of the L3 vertebrae and the QCT BMD value of the patients (r = 0.95, P < 0.001). However, there was no significant correlation between containing cortical bone overall HU value and containing osteophyte overall HU value and the patient's QCT BMD value (P > 0.05). CONCLUSIONS: Vertebral HU value is an alternative measurement that effectively reflects the patient's BMD. In middle-aged and elderly LDD patients, HU values in different areas of L3 vertebra are significantly different, and hyperplastic tissues such as cortical bone and osteophytes may exponentially lead to higher HU value in patients. Compared with other measurement areas, vertebral cancellous bone HU value have the advantage of accurately assessing patients' BMD.

Serial intravitreal injections in age-related macular degeneration patients from the dry eye disease perspective: a cross-sectional study.

BACKGROUND: To evaluate the effects of serial intravitreal injections (IVI) on the ocular surface and meibomian glands in patients with neovascular age-related macular degeneration (nAMD). METHODS: Patients receiving anti-vascular endothelial growth factor (anti-VEGF) agent injections for unilateral nAMD were included. Untreated fellow eyes served as the control group. All participants followed a pre-IVI asepsis protocol with povidone-iodine (PI). Ocular surface diseases index (OSDI) questionnaire scores, first and average non-invasive tear break-up time (fNITBUT and avgNITBUT), Schirmer-1 test results, corneal staining score (according to Oxford scale), meibomian gland (MG) loss rates of lower and upper eyelids were recorded four weeks after the last IVI. RESULTS: Forty-two nAMD patients with a mean age of 63.3 ± 19.4 were included in the study. The mean OSDI score was 20.3 and the median of IVI number was 9 (6-22). There were no statistically significant difference between treated and untreated fellow eyes regarding fNITBUT (5.6 vs. 4.5, p = 0.872), avgNITBUT (6.2 vs. 7.2, p = 0.968), Shirmer-1 results (7 vs. 7, p = 0.854), corneal staining (0.3 vs. 0.2, p = 0.341), lower and upper MG loss rate (29.3 vs. 28.4, p = 0.162, and 27.1 vs. 26.9, p = 0.476, respectively). Only significant correlation was observed between age with lower and upper MG loss rate (r:0.396, p = 0.042, and r:0.365, p = 0.047). CONCLUSION: The results of the present study demonstrated that serial IVI of anti-VEGF agents with PI asepsis is well tolerated by nAMD patients in terms of ocular surface, MG loss and DED measurements.

Magnetic resonance imaging classification in a percutaneous needle injury rat model of intervertebral disc degeneration.

BACKGROUND: During the development of disease-modifying intervertebral disc degeneration (IDD) drugs, the rat model of IDD is frequently used for disease progression assessment. The aim of this study was to describe a magnetic resonance (MRI) scoring system for the assessment of different disc conditions in puncture-induced IDD, allowing standardization and comparison of results obtained by different investigators. METHODS: A total of 36 Sprague-Dawley rats were utilized in the present study. The animals were divided into two groups: a sham group and an IDD group caused by puncture. The rats in the IDD group were subsequently divided into six categories based on time frames, with five rats in each category. The sham group was divided into two sub-groups (n = 3) for 28 and 56 days, respectively. T2-weighted images of rats consecutively studied with MRI of the coccygeal discs were classified according to the time course using the corresponding histological data. Additional scoring of the micro-CT was employed to identify the progression of bone destruction of the rat model of IDD. RESULTS: A comparison of the MRI results between the sham group and the IDD group revealed a significant reduction in NP height, area, T2WI value, and DHI in the latter group (P < 0.05). The micro-CT results demonstrated that following acupuncture, there was a notable decline in the BV, Tb.N, and height of the coccygeal vertebra, while the BS/BV and Tb.Sp exhibited a significant increase (P < 0.05). The histological results were analogous to the MRI results, indicating a progressive exacerbation of IDD and a corresponding increase in NP score (P < 0.05). The results of the MRI were found to be consistent with those of the micro-CT and histological analyses (P < 0.05). The results of the study demonstrate a robust correlation between MRI analysis and histological findings. Live animals are employed for MRI analysis to improve experiment comparability. The reliability of the MRI scoring system ensures assessment of disease progression in live animals, while promoting cost savings and animal welfare by avoiding the sacrifice of animals at different times. CONCLUSIONS: The described scoring paradigm has quantitatively been found to differentiate IDD disease progression in an in vivo rat model. Hence, we suggest employing it to evaluate the rat IDD model and assess the effects of treatments in this model.

Gut microbiome dysbiosis is associated with lumbar degenerative spondylolisthesis in symptomatic patients.

Background: Lumbar degenerative spondylolisthesis (LDS), characterized as degeneration of the intervertebral disc and structural changes of the facet joints, is a condition with varying degrees of instability that may lead to pain, canal stenosis, and subsequent surgical intervention. However, the etiology of LDS remains inconclusive. Gut microbiome dysbiosis may stimulate systemic inflammation in various disorders. However, the role of such dysbiosis upon spine health remains under-studied. The current study assessed the association of gut microbiome dysbiosis in symptomatic patients with or without LDS. Methods: A cross-sectional analysis within the framework of a prospective study was performed. DNA was extracted from fecal samples collected from adult symptomatic patients with (n = 21) and without LDS (n = 12). Alpha and beta diversity assessed differences in fecal microbial community between groups. Taxon-by-taxon analysis identified microbial features with differential relative abundance between groups. Subject demographics and imaging parameters were also assessed. Results: There was no significant group differences in age, sex, race, body mass index, smoking/alcohol history, pain profiles, spinopelvic alignment, and Modic changes (p >0.05). LDS subjects had significantly higher disc degeneration severity (p = 0.018) and alpha diversity levels compared to non-LDS subjects (p = 0.002-0.003). Significant differences in gut microbial community structure were observed between groups (p = 0.046). Subjects with LDS exhibited distinct differences at the phylum level, with a significantly higher Firmicutes to Bacteroidota ratio compared to non-LDS (p = 0.003). Differential relative abundance analysis identified six taxa with significant differences between the two groups, with LDS demonstrating an increase in putative pro-inflammatory bacteria (Dialister, CAG-352) and a decrease in anti-inflammatory bacteria (Slackia, Escherichia-Shigella). Conclusion: This study is the first to report a significant association of gut microbiome dysbiosis and LDS in symptomatic patients, noting pro-inflammatory bacterial taxa. This work provides a foundation for future studies addressing the role of the gut microbiome in association with spine health and disease.

Total joint replacement of the lumbar spine: report of the first two cases with 16 years of follow-up.

Background: Total joint replacement (TJR) of the lumbar spine is a revolutionary procedure that couples the clinical benefits of neural decompression with preservation of natural motion and sagittal balance at the operative level. The TJR procedure involves reconstruction of the entire motion segment using a posterior bilateral transforaminal approach to access the disc space. The TJR implant (MOTUS, 3Spine, Chattanooga, TN, USA) replaces the function of the intervertebral disc and facet joints, performing biomechanically as a new articulation for the resected, degenerated disc and facets. The implant has been optimized to simulate the kinematic characteristics of the three-joint complex. Case Description: Two male patients, ages 32 and 38 years, underwent the first TJR procedures in 2007 in South Africa. Both patients had imaging evidence of advanced spinal degeneration with unremitting back and leg pain refractory to conservative management. Symptom amelioration was achieved postoperatively with markedly reduced pains scores and improved function at clinical follow-up. Both cases were recently re-examined after 16 years and the patients reported that the procedure significantly changed their lives. Neither believes they have a lingering back condition and they have been able to fully participate in all functions related to work, family and recreation. There was little to no imaging evidence of adjacent segment disease or arthritic changes at this long-term follow-up interval. Conclusions: After 16 years of clinical follow-up, the implant continues to function normally, without evidence of adjacent segment degeneration and both patients continue to enjoy activities of daily living without back or leg pain or other functional impairments.