Citations

Objective: Chronic nonspecific low back pain (CNLBP) is a serious medical and social problem resulting in functional decline and decreased work ability. Tuina, a form of manual therapy, has been sparsely used to treat patients with CNLBP. To systematically assess the efficacy and safety of Tuina for patients with CNLBP. Methods: Multiple English and Chinese literature databases were searched until September 2022 for randomized controlled trials (RCTs) of Tuina in the treatment of CNLBP. The methodological quality was assessed using the Cochrane Collaboration’s tool, and certainty of the evidence was determined with the online Grading of Recommendations, Assessment, Development and Evaluation tool. Results: Fifteen RCTs with 1390 patients were included. Tuina demonstrated a significant effect on pain (SMD: −0.82; 95% CI −1.12 to −0.53; P < .001; I 2 = 81%) and physical function (SMD: −0.91; 95% CI −1.55 to −0.27; P = .005; I 2 = 90%) when compared to control. However, Tuina resulted in no significant improvement for quality of life (QoL) (SMD: 0.58; 95% CI −0.04 to 1.21; P = .07; I 2 = 73%;) compared to control. The Grading of Recommendations, Assessment, Development and Evaluation evidence quality was determined to be low level for pain relief, physical function, and QoL measurements. Only six studies reported adverse events; none were serious. Conclusion: Tuina might be an effective and safe strategy for treating CNLBP in terms of pain and physical function, but not for QoL. The study results should be interpreted with caution for their low-level evidence. More multicenter, large-scale RCTs with a rigorous design are required to further confirm our findings.

AbstractPelvic organ prolapse (POP) is a dysfunction that affects a large proportion of women. Current support scaffolds’ lack of biocompatibility, biodegradability, and mechanical compliance are associated with surgical complications including erosion and pain, indicating the urgent need for new tissue scaffolds with customizable functions. A new material that uses polyvinyl alcohol (PVA) as the main ingredient and is chemically tuned to possess suitable mechanical properties and degradation rates for the surgical treatment of POP is developed. Specifically, the thiol‐norbornene “click” chemistry enables the sol‐gel transition of the biomaterial under UV‐light without side‐products. Meanwhile, NaOH treatment further toughens the hydrogel with a higher crosslink density. The PVA‐based biocompatible ink can be printed with UV‐facilitated direct ink writing due to the rapidly UV‐initiated chemical crosslink; in situ image analysis and machine learning methods are applied during this procedure to quantify and improve the printing quality. The cell viability results demonstrate the biocompatibility of the POP scaffolds, suggesting the potential for future animal studies and the possibility of clinical research. This study bridges polymer chemistry and manufacturing engineering with a specific tissue engineering application to solve the common disorder of POP, shedding light on individualized medicine and intelligent systems for biomedical engineering.

ImportanceGlaucoma can develop following cataract removal in children.ObjectiveTo assess the cumulative incidence of glaucoma-related adverse events (defined as glaucoma or glaucoma suspect) and factors associated with risk of these adverse events in the first 5 years after lensectomy prior to 13 years of age.Design, Setting, and ParticipantsThis cohort study used longitudinal registry data collected at enrollment and annually for 5 years from 45 institutional and 16 community sites. Participants were children aged 12 years or younger with at least 1 office visit after lensectomy from June 2012 to July 2015. Data were analyzed from February through December 2022.ExposuresUsual clinical care after lensectomy.Main Outcomes and MeasuresThe main outcomes were cumulative incidence of glaucoma-related adverse events and baseline factors associated with risk of these adverse events.ResultsThe study included 810 children (1049 eyes); 443 eyes of 321 children (55% female; mean [SD] age, 0.89 [1.97] years) were aphakic after lensectomy, and 606 eyes of 489 children (53% male; mean [SD] age, 5.65 [3.32] years) were pseudophakic. The 5-year cumulative incidence of glaucoma-related adverse events was 29% (95% CI, 25%-34%) in 443 eyes with aphakia and 7% (95% CI, 5%-9%) in 606 eyes with pseudophakia; 7% (95% CI, 5%-10%) of aphakic eyes and 3% (95% CI, 2%-5%) of pseudophakic eyes were diagnosed as glaucoma suspect. Among aphakic eyes, a higher risk for glaucoma-related adverse events was associated with 4 of 8 factors, including age less than 3 months (vs ≥3 months: adjusted hazard ratio [aHR], 2.88; 99% CI, 1.57-5.23), abnormal anterior segment (vs normal: aHR, 2.88; 99% CI, 1.56-5.30), intraoperative complications at time of lensectomy (vs none; aHR, 2.25; 99% CI, 1.04-4.87), and bilaterality (vs unilaterality: aHR, 1.88; 99% CI, 1.02-3.48). Neither of the 2 factors evaluated for pseudophakic eyes, laterality and anterior vitrectomy, were associated with risk of glaucoma-related adverse events.Conclusions and RelevanceIn this cohort study, glaucoma-related adverse events were common after cataract surgery in children; age less than 3 months at surgery was associated with elevated risk of the adverse events in aphakic eyes. Children with pseudophakia, who were older at surgery, less frequently developed a glaucoma-related adverse event within 5 years of lensectomy. The findings suggest that ongoing monitoring for the development of glaucoma is needed after lensectomy at any age.

AbstractObjectiveIn this observational study on a cohort of biopsy‐proven central nervous system demyelinating disease consistent with MS, we examined the relationship between early‐active demyelinating lesion immunopattern (IP) with subsequent clinical course, radiographic progression, and cognitive function.MethodsSeventy‐five patients had at least one early‐active lesion on biopsy and were pathologically classified into three immunopatterns based on published criteria. The median time from biopsy at follow‐up was 11 years, median age at biopsy ‐ 41, EDSS ‐ 4.0. At last follow‐up, the median age was 50, EDSS ‐ 3.0. Clinical examination, cognitive assessment (CogState battery), and 3‐Tesla‐MRI (MPRAGE/FLAIR/T2/DIR/PSIR/DTI) were obtained.ResultsIP‐I was identified in 14/75 (19%), IP‐II was identified in 41/75 (56%), and IP‐III was identified in 18/75 (25%) patients. Patients did not differ significantly by immunopattern in clinical measures at onset or last follow‐up. The proportions of disease courses after a median of 11 years were similar across immunopatterns, relapsing–remitting being most common (63%), followed by monophasic (32%). No differences in volumetric or DTI measures were found. CogState performance was similar for most tasks. A slight yet statistically significant difference was identified for episodic memory scores, with IP‐III patients recalling one word less on average.InterpretationIn this study, immunopathological heterogeneity of early‐active MS lesions identified at biopsy does not correlate with different long‐term clinical, neuroimaging or cognitive outcomes. This could be explained by the fact that while active white matter lesions are pathological substrates for relapses, MS progression is driven by mechanisms converging across immunopatterns, regardless of pathogenic mechanisms driving the acute demyelinated plaque.

Abstract Background Computed tomography enterography (CTE) is frequently used to assess stricturing Crohn’s disease (CD). However, the reliability of CTE items used for assessment has not been established and there is no validated radiologic stricture severity index. Methods We conducted a retrospective study of 43 patients with symptomatic, terminal ileal stricturing CD. Four radiologists assessed a comprehensive list of pre-defined radiologic items potentially associated with stricture severity in 48 CTE scans in two separate rounds in random order. Reliability was quantified using the intraclass correlation coefficient (ICC). Items with at least moderate (ICC≥0.41) inter-rater reliability that were correlated with a visual analogue scale of overall stricture severity were candidate items for the development of a CTE stricture index. Results Inter-rater reliability was almost perfect for assessment of luminal diameter of pre-stenotic dilation (ICC 0.817 [95% confidence interval 0.703, 0.878]), substantial for stricture length (ICC 0.628 [0.419, 0.797]), and moderate for stricture wall thickness (0.482 [0.330, 0.601]). Intra-rater reliability was almost perfect (ICC ≥ 0.850) for all three items. A stricture severity index was derived and was well calibrated (optimism-adjusted calibration slope = 1.009), with scores calculated as the sum of stricture length (cm) + luminal diameter of pre-stenotic dilation (mm) + 5 x stricture wall thickness (mm). Conclusion Stricture length, prestenotic dilation, and stricture wall thickness can be reliably assessed, and are component items for a novel CTE stricture index (CTE-SI) of stricture severity for CD-related terminal ileal strictures. Additional external index validation for clinical and research contexts is required.

Abstract Eosinophils play a surprising role in downregulating lung graft-specific alloimmunity, even without immunosuppression. We demonstrate here, a mechanism used by eosinophils to downregulate alloimmune responses. To study the mechanism of eosinophil dependent downregulation of alloimmune responses, we used a model of diphtheria toxin (DT) dependent ablation of eosinophils in iPHIL, a mouse model expressing DT receptor on the eosinophil-peroxidase gene locus. Fully MHC-mismatched Balb/c (H2Kd) lungs were engrafted to iPHIL (H2Kb) recipients without immunosuppression. We modeled alloreactivity in vitro, with mixed leukocyte cultures, comprising Th1-polarized eosinophils as modulators of T cells from C57BL/6J or Nur77-GFP mice stimulated by either allogeneic dendritic cells or anti-CD3/CD28 agonistic antibodies. Ablation of eosinophils in non-immunosuppressed lung graft recipients leads to enhanced T cell activation and graft rejection. Similarly, in vitro, we observed a dose and contact dependent downregulation of T cell activation by eosinophils. While contact between eosinophils and T cells is mediated through the upregulation of PD-L1 on both wild-type and iNOS−/− eosinophils after TH-1 polarization, the inhibition of T cell activation is iNOS dependent and is directly linked to the iNOS dependent inhibition of the TCR signaling early gene, Nr4a1, monitored in Nur77-GFP mice. Thus, following contact with T cells, iNOS-expressing eosinophils downregulate lung graft alloimmunity through a direct effect on TCR engagement early genes, leading to the inhibition of T cell activation. This provides an explanation for the surprising observation of lung-graft specific alloimmune downregulation by eosinophils.

Background: We evaluated imaging features suggestive of neurodegeneration within the brainstem and upper cervical spinal cord (UCSC) in non-progressive multiple sclerosis (MS). Methods: Standardized 3-Tesla three-dimensional brain magnetic resonance imaging (MRI) studies were prospectively acquired. Rates of change in volume, surface texture, curvature were quantified at the pons and medulla-UCSC. Whole and regional brain volumes and T2-weighted lesion volumes were also quantified. Independent regression models were constructed to evaluate differences between those of Black or African ancestry (B/AA) and European ancestry (EA) with non-progressive MS. Results: 209 people with MS (pwMS) having at least two MRI studies, 29% possessing 3–6 timepoints, resulted in 487 scans for analysis. Median follow-up time between MRI timepoints was 1.33 (25th–75th percentile: 0.51–1.98) years. Of 183 non-progressive pwMS, 88 and 95 self-reported being B/AA and EA, respectively. Non-progressive pwMS demonstrated greater rates of decline in pontine volume ( p < 0.0001) in B/AA and in medulla-UCSC volume ( p < 0.0001) for EA pwMS. Longitudinal surface texture and curvature changes suggesting reduced tissue integrity were observed at the ventral medulla-UCSC ( p < 0.001), dorsal pons ( p < 0.0001) and dorsal medulla ( p < 0.0001) but not the ventral pons ( p = 0.92) between groups. Conclusions: Selectively vulnerable regions within the brainstem-UCSC may allow for more personalized approaches to disease surveillance and management.

PurposeTo improve calibrationless parallel imaging using pre‐learned subspaces of coil sensitivity functions.Theory and MethodsA subspace‐based joint sensitivity estimation and image reconstruction method was developed for improved parallel imaging with no calibration data. Specifically, we proposed to use a probabilistic subspace model to capture prior information of the coil sensitivity functions from previous scans acquired using the same receiver system. Both the subspace basis and coefficient distributions were learned from a small set of training data. The learned subspace model was then incorporated into the regularized reconstruction formalism that includes a sparsity prior. The nonlinear optimization problem was solved using alternating minimization algorithm. Public fastMRI brain dataset was retrospectively undersampled by different schemes for performance evaluation of the proposed method.ResultsWith no calibration data, the proposed method consistently produced the most accurate coil sensitivity estimation and highest quality image reconstructions at all acceleration factors tested in comparison with state‐of‐the‐art methods including JSENSE, DeepSENSE, P‐LORAKS, and Sparse BLIP. Our results are comparable to or even better than those from SparseSENSE, which used calibration data for sensitivity estimation. The work also demonstrated that the probabilistic subspace model learned from T2w data can be generalized to aiding the reconstruction of FLAIR data acquired from the same receiver system.ConclusionA subspace‐based method named JSENSE‐Pro has been proposed for accelerated parallel imaging without the acquisition of companion calibration data. The method is expected to further enhance the practical utility of parallel imaging, especially in applications where calibration data acquisition is not desirable or limited.