OBJECTIVE: This study analyzed and explored the relationship between isthmic spondylolisthesis and disc degeneration by comparing the degree of disc degeneration in patients with isthmic spondylolisthesis, lumbar disc herniation, and asymptomatic healthy individuals.
METHODS: This study included a total of 138 cases, consisting of L5-S1 single segment lesion patients and a normal lumbar spine population. The cases were divided into 3 groups based on the type of disease: fifty eight cases in the isthmic spondylolisthesis (IS) group, 50 cases in the lumbar disc herniation (LDH) group, and 30 cases in the normal lumbar vertebrae (NLV) group.
RESULTS: The research findings indicate that the proportion of intervertebral disc degeneration in the LDH group is significantly higher than that in the IS group and NLV group (65.3% vs. 33.3% vs. 25.8%, P < 0.05). The Pfirrmann grades of lumbar intervertebral discs (L1-L4) in the LDH group are significantly higher than those in the IS group and NLV group (P < 0.05), and the intervertebral height index (IHI) (L1-L4) of lumbar vertebrae in the LDH group is significantly lower than that in the IS group and NLV group (P < 0.05).
CONCLUSIONS: The results showed that the degree of intervertebral disc degeneration in patients with isthmic spondylolisthesis was lighter than that in patients with LDH, and even similar to that in healthy individuals. The occurrence of IS may have slowed down the degeneration of nonaffected segment intervertebral discs through certain factors.

OBJECTIVE: This study aimed to assess the prevalence and associated factors of corneal opacity among adults in Kolladiba town, Northwest Ethiopia.
METHODS: A community-based cross-sectional study was conducted using a systematic random sampling technique. A total of 846 adult individuals were recruited for the study. Ethical approval was obtained from the University of Gondar School of Medicine Ethical Review Committee. A standardised, semistructured questionnaire plus an ocular examination were used to collect the data. The data were entered into Epi Info V.7 and cleaned and analysed using SPSS V.26. Binary and multivariable logistic regression analyses were performed to select candidate variables and identify statistically significant factors. Variables with a p value of less than 0.05 according to the multivariable logistic regression analysis were considered to be statistically significant.
CONCLUSIONS: The prevalence of corneal opacity among the study participants was 27.2% (95% CI 24.4% to 30.4%). In this study, age 49-60 years (adjusted OR (AOR): 1.90; 95% CI 1.03 to 3.32), age ≥61 years (AOR=2.12; 95% CI 1.17 to 3.87), inability to read and write (AOR=2.65; 95% CI 1.68 to 4.16), middle-income level (AOR=2.12; 95% CI 1.30 to 3.47) and poor income level (AOR=4.96; 95% CI 3.04 to 8.09) were factors that were significantly associated with corneal opacity.In this study, the prevalence of corneal opacity was considerably high. Being poor and unable to read and write were the primary factors significantly associated with corneal opacity. Hence, concerned stakeholders should strive to reverse the effects of corneal opacity on the quality of life of the study and causal studies should be considered in the future.

OBJECTIVE: Despite significant advances in clinical care and understanding of the underlying pathophysiology, age-related macular degeneration (AMD)-a major cause of global blindness-lacks effective treatment to prevent the irreversible degeneration of photoreceptors leading to central vision loss. Limited studies suggest phosphodiesterase type 5 (PDE5) inhibitors, such as sildenafil, may prevent AMD by increasing retinal blood flow. This study explores the potential association between sildenafil use and AMD risk in men with erectile dysfunction using UK data.
METHODS: Using the UK\'s IQVIA Medical Research Data, the study analysed 31 575 men prescribed sildenafil for erectile dysfunction and no AMD history from 2007 to 2015, matched with a comparator group of 62 155 non-sildenafil users in a 1:2 ratio, over a median follow-up of approximately three years.
RESULTS: The primary outcome was the incidence of AMD in the two groups. The study found no significant difference in AMD incidence between the sildenafil users and the non-users, with an adjusted hazard ratio (HR) of 0.99 (95% CI 0.84 to 1.16), after accounting for confounders such as age, ethnicity, Townsend deprivation quintile, body mass index category, and diagnosis of hypertension and type 2 diabetes.
CONCLUSIONS: The study results indicated no significant association between sildenafil use and AMD prevention in UK men with erectile dysfunction, suggesting sildenafil\'s protective effect on AMD is likely insignificant.

UNASSIGNED: Intervertebral disk (IVD) degeneration usually occurs earlier in chondrodystrophic dog breeds than in other breeds. Spinal cord compression secondary to IVD degeneration is the most common cause of myelopathy in these dogs. Standard magnetic resonance imaging (MRI) sequences permit the identification of IVD degeneration and its consequences on adjacent neurological structures. In human medicine, quantitative MRI sequences, such as magnetization transfer ratio (MTR) sequences, are developed and used to detect early IVD degeneration. This prospective randomized post-mortem comparative study aimed to evaluate the correlation between a qualitative Pfirrmann MRI grading and the MTR values of the IVD in chondrodystrophic dogs.
UNASSIGNED: Vertebral columns of eight canine cadavers were frozen and thawed prior to imaging with T2-weighted and MTR sequences using a 3.0 T high-field MRI. These sequences were reviewed by two observers. A Spearman correlation coefficient was calculated in order to compare the MTR values with the Pfirrmann grade. Pearson correlation coefficients were calculated to evaluate the inter-observer agreement of the delineation of the region of interest (ROI) around the NP and the MTR values. A Wilcoxon-Mann-Whitney test was used to conclude on the significance of the correlation between the MTR values and the Pfirrmann grades.
UNASSIGNED: There were 138 intervertebral disks analyzed: 29/138 (21.0%) IVD were grade I, 74/138 (53.6%) grade II, and 35/138 (25.4%) grade III. No grades IV and V were present in this study. Inter-observer agreement for delineation of IVD ROI was fair (r = 0.54) but inter-observer agreement of mean MTR value within the ROI was very good (r = 0.89). Mean MTR values were 16.459% (10.0305-21.0950%) for grade I, 18.888% (10.0750-27.2400%) for grade II, and 22.813% (12.5700-31.7600%) for grade III. The mean MTR value was significantly different between each Pfirrmann grade: between grades I and II (p < 0.005), grades II and III (p < 0.05), and grades I and III (p < 0.005). There was a significant moderate positive correlation between Pfirrmann grading and mean MTR values (r = 0.516).
UNASSIGNED: The magnetization transfer ratio seems to be an objective method to detect early intervertebral disk degeneration via quantitative analysis.

OBJECTIVE: This study aims to analyse the effect of diabetes mellitus (DM) on the radiological changes of Magnetic Resonance Imaging (MRI) on the intervertebral discs and paravertebral muscle to investigate the effect of DM on spinal degeneration.
METHODS: This retrospective study initially included 262 patients who underwent treatment between January 2020 and December 2021 because of lumbar disc herniation. Amongst these patients, 98 patients suffered from type 2 diabetes mellitus (T2DM) for more than five years; this is the poorly controlled group (haemoglobin A1c (HbA1c) ≥ 6.5%; BMI: 26.28 ± 3.60; HbA1c: 7.5, IQR = 1.3). Another 164 patients without T2DM are included in the control group. The data collected and analysed include gender, age, smoking, alcohol use, disease course, Charlson Comorbidity Index, BMI, and radiological parameters including disc height, modified Pfirrmann grading scores, percentage of fat infiltration area of paravertebral muscle, and pathological changes of the endplate.
RESULTS: After propensity score-matched analysis, the difference in general data between the control and T2DM groups was eliminated, and 186 patients were analysed. The modified Pfirrmann grading scores showed statistical differences in every lumbar segment, suggesting that the T2DM group suffered from greater disc degeneration at all L1-S1 segments compared with the control group. The disc height from L1/2 to L5/S1 was not statistically different between the two groups. Compared to the T2DM group, the control group had a lower percentage of fat infiltration areas in L4/5 and L5/S1 paravertebral muscle, whereas L1/2 to L3/4 showed no statistical difference. The T2DM group had more pathological changes of cartilage endplate compared with the control group.
CONCLUSIONS: Prolonged uncontrolled hyperglycaemia may contribute to lumbar disc degeneration, fatty infiltration of the paraspinal muscles in the lower lumbar segments, and increased incidence of endplate cartilage pathological changes in patients with degenerative disc disease.

OBJECTIVE: To investigate whether PIEZO-intracytoplasmic sperm injection (PIEZO-ICSI) increases the fertilization rate, decreases the degeneration rate, and increases the utilization rate per oocyte injected compared with conventional intracytoplasmic sperm injection (ICSI).
METHODS: Sibling oocyte split multicenter trial.
METHODS: Fertility clinics.
METHODS: Women with a diagnosis of infertility who used ICSI as their method of insemination and had ≥6 mature oocytes for injection.
METHODS: Participants had their mature oocyte cohort divided, where half were injected using conventional ICSI and the other half were injected using PIEZO-ICSI. For patients with an uneven oocyte number, the extra oocyte was injected using conventional ICSI. The injection technique used first was also randomized to ensure that there was no bias due to order of injection.
METHODS: The primary outcome measure was the fertilization rate after injection.
RESULTS: A total of 108 patients underwent a sibling split use of conventional ICSI and PIEZO-ICSI. The fertilization rate was 71.6% in PIEZO-ICSI, which significantly increased compared with that in conventional ICSI 65.6%. In addition, the oocyte degeneration rate decreased in PIEZO-ICSI compared with that in conventional ICSI (6.3% vs. 12.1% respectively), and the blastocyst quality increased, as measured by the number of grade A and B quality blastocysts present on day 5 of development (33.3% vs. 27.5%). No significant differences in the aneuploidy or utilization rate, clinical pregnancy, or live birth outcome after single embryo transfer were noted between the two injection techniques.
CONCLUSIONS: This trial supports the possibility that PIEZO-ICSI increases the fertilization rates, decreases the oocyte degeneration rates, and increases the blastocyst quality compared with conventional ICSI; however, it does not appear to influence the clinical pregnancy or live birth rate per transfer.
UNASSIGNED: Australian and New Zealand Clinical Trial Registry ACTRN12620000407998.

BACKGROUND: Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system that causes myelin sheath damage and axonal degeneration. The glycolipid (2S, 3S, 4R)-1-O-(α-d-galactosyl)-2-tetracosanoylamino-1,3,4-nonaetriol (OCH-NCNP1 or OCH) exerts an immunoregulatory action that suppresses T helper (Th)1 cell-mediated immune responses through natural killer T cell activation, selective interleukin-4 production, and Th2 bias induction in human CD4-positive natural killer T cells.
OBJECTIVE: This trial aims to investigate the efficacy and safety of the immunomodulator OCH in patients with relapsing MS through 24-week repeated administration.
METHODS: This protocol describes a double-blind, multicenter, placebo-controlled, randomized phase II clinical trial that was initiated in September 2019. The participants were randomly assigned to either a placebo control group or an OCH-NCNP1 group and the investigational drug (3.0 mg) was orally administered once weekly for the 24-week duration. Major inclusion criteria are as follows: patients had been diagnosed with relapsing MS (relapsing-remitting and/or secondary progressive MS) based on the revised McDonald criteria or were diagnosed with MS by an attending physician as noted in their medical records; patients with at least two medically confirmed clinical exacerbations within 24 months prior to consent or one exacerbation within 12 months prior to consent; patients with at least one lesion suspected to be MS on screening magnetic resonance imaging (MRI); and patients with 7 points or less in the Expanded Disability Status Scale during screening. Major exclusion criteria are as follows: diagnosis of neuromyelitis optica and one of optic neuritis, acute myelitis, and satisfying at least two of the following three items: (1) spinal cord MRI lesion extending across at least three vertebral bodies, (2) no brain MRI lesions during onset (at least four cerebral white matter lesions or three lesions, one of which is around the lateral ventricle), and (3) neuromyelitis optica-immunoglobulin G or antiaquaporin-4 antibody-positive. Outcome measures include the primary outcome of MRI changes (the percentage of subjects with new or newly expanded lesions at 24 weeks on T2-weighted MRI) and the secondary outcomes annual relapse rate (number of recurrences per year), relapse-free period (time to recurrence), sustained reduction in disability (SRD) occurrence rate, period until SRD (time to SRD occurrence), no evidence of disease activity, and exploratory biomarkers from phase I trials (such as gene expression, cell frequency, and intestinal and oral microbiome).
RESULTS: We plan to enroll 30 patients in the full analysis set. Enrollment was closed in June 2021 and the study analysis was completed in March 2023.
CONCLUSIONS: This randomized controlled trial will determine whether OCH-NCNP1 is effective and safe in patients with MS as well as provide evidence for the potential of OCH-NCNP1 as a therapeutic agent for MS.
BACKGROUND: ClinicalTrials.gov NCT04211740; https://clinicaltrials.gov/study/NCT04211740.
UNASSIGNED: DERR1-10.2196/46709.

To evaluate efficacy, safety, pharmacokinetics (PK) and immunogenicity of SB15 versus reference aflibercept (AFL), and switching from AFL to SB15 in neovascular age-related macular degeneration (nAMD).
Prospective, double-masked, randomised, phase 3 trial.
Participants with nAMD were randomised 1:1 to receive SB15 (N=224 participants) or AFL (N=225). At week 32, participants either continued on SB15 (SB15/SB15, N=219) or AFL (AFL/AFL, N=108), or switched from AFL to SB15 (AFL/SB15, N=111). This manuscript reports 1-year and switching results of secondary efficacy endpoints such as changes from baseline to week 56 in best-corrected visual acuity (BCVA), central subfield thickness (CST, from internal limiting membrane (ILM) to retinal pigment epithelium), and total retinal thickness (TRT, from ILM to Bruch\'s membrane). Additional endpoints included safety, PK and immunogenicity.
Efficacy results were comparable between groups. The least squares mean (LSmean) change in BCVA from baseline to week 56 was 7.4 letters for SB15/SB15 and 7.0 letters for AFL/AFL (difference (95% CI)=0.4 (-2.5 to 3.2)). The LSmean changes from baseline to week 56 in CST and TRT were -119.2 µm and -132.4 µm for SB15/SB15 and -126.6 µm and -136.3 µm for AFL/AFL, respectively (CST: difference (95% CI)=7.4 µm (-6.11 to 20.96); TRT: difference (95% CI)=3.9 µm (-18.35 to 26.10)). Switched and non-switched participants showed similar LSmean changes in BCVA from baseline to week 56 (AFL/SB15, 7.9 letters vs AFL/AFL, 7.8 letters; difference (95% CI)=0.0 (-2.8 to 2.8)). Safety, PK and immunogenicity were comparable between groups.
Efficacy, safety, PK and immunogenicity were comparable between SB15 and AFL and between switched and non-switched participants.

OBJECTIVE: We performed a prospective one-year multi-imaging study to assess the clinical outcomes and rate of disc resorption in acute lumbar disc herniation (LDH) patients undergoing inflammation-preserving treatment (i.e. no NSAIDS, steroids).
METHODS: All patients received gabapentin to relieve leg pain, 12 sessions of acupuncture. Repeat MRI was performed, every 3 months, after 12 sessions of treatment continued for those without 40% reduction in herniated disc sagittal area. Disc herniations sizes were measured on sagittal T2W MRI sequences, pre-treatment and at post-treatment intervals. Patients were stratified to fast, medium, slow, and prolonged recovery groups in relation to symptom resolution and disc resorption.
RESULTS: Ninety patients (51% females; mean age: 48.6 years) were assessed. Mean size of disc herniation was 119.54 ± 54.34 mm2, and the mean VAS-Leg score was 6.12 ± 1.13 at initial presentation. A total of 19 patients (21.1%) improved at the time of the repeat MRI (i.e. within first 3 months post-treatment). 100% of all patient had LDH resorption within one year (mean: 4.4. months). There was no significant difference at baseline LDH between fast, medium, slow, and prolonged resorption groups. Initial LDH size was weakly associated with degree of leg pain at baseline and initial gabapentin levels. Surgery was avoided in all cases.
CONCLUSIONS: This is the first study to note inflammation-preserving treatment, without conventional anti-inflammatory and steroid medications, as safe and effective for patients with an acute LDH. Rate of disc resorption (100%) was higher than comparative recent meta-analysis findings (66.7%) and no patient underwent surgery.

OBJECTIVE: Adenomyosis is associated with unfavorable perinatal outcomes, and recent case reports show that some women with adenomyosis experience pain at the adenomyosis lesion during pregnancy and have detrimental perinatal outcomes. This study aimed to clarify the clinical characteristics of this pain and perinatal outcomes associated with this phenomenon.
METHODS: This was a single-center retrospective analysis of pregnant women with adenomyosis. The incidence of pain onset at adenomyosis lesions, defined as persistent pain at the adenomyosis site with administration of analgesics for pain relief, and its association with perinatal outcomes were analyzed.
RESULTS: Among 91 singleton pregnancies with adenomyosis, 12 pregnancies (13.2 %) presented with pain. One pregnancy resulted in second-trimester miscarriage, and 5 of the 11 pregnancies (45 %) developed preeclampsia, which resulted in preterm delivery, and 3 of the 12 pregnancies (25 %) achieved term delivery. The incidence of preeclampsia and preterm delivery was higher in those who experienced pain than in those without (45 % [5/11] vs. 15 % [11/74]; p<0.05, and 73 % [8/11] vs. 34 % [25/74]; p<0.05, respectively). Among women with pain, the maximum C-reactive protein level was significantly higher in women who developed preeclampsia than in those who did not (5.45 vs. 0.12 mg/dL, p<0.05).
CONCLUSIONS: Our study revealed that adenomyosis can cause pain in over one of eight pregnancies with adenomyosis, which may be associated with the increased incidence of preeclampsia resulting in preterm delivery. Women with pain, especially those with high C-reactive protein levels, may be at high risk for future development of preeclampsia and consequent preterm delivery.