Rehabilitation to Improve Outcomes after Cervical Spine Surgery: Narrative Review.

PURPOSE: The increasing elderly patient population is contributing to the rising worldwide load of cervical spinal disorders, which is expected to result in a global increase in the number of surgical procedures in the foreseeable future. Cervical rehabilitation plays a crucial role in optimal recovery after cervical spine surgeries. Nevertheless, there is no agreement in the existing research regarding the most suitable postsurgical rehabilitation program. Consequently, this review assesses the ideal rehabilitation approach for adult patients following cervical spine operations. MATERIALS AND METHODS: This review covers activities of daily living and encompasses diverse treatment methods, including physiotherapy, specialized tools, and guidance for everyday activities. The review is organized under three headings: (1) historical perspectives, (2) patient-reported functional outcomes, and (3) general and disease-specific rehabilitation. RESULTS: Rehabilitation programs are determined on the basis of patient-reported outcomes, performance tests, and disease prognosis. CSM requires strengthening of the neck and shoulder muscles that have been surgically invaded. In contrast, the CCI requires mobility according to the severity of the spinal cord injury and functional prognosis. The goal of rehabilitation for CCTs, as for CCIs, is to achieve ambulation, but the prognosis and impact of cancer treatment must be considered. CONCLUSIONS: Rehabilitation of the cervical spine after surgery is essential for improving physical function and the ability to perform daily activities and enhancing overall quality of life. The rehabilitation process should encompass general as well as disease-specific exercises. While current rehabilitation protocols heavily focus on strengthening muscles, they often neglect the crucial aspect of spinal balance. Therefore, giving equal attention to muscle reinforcement and the enhancement of spinal balance following surgery on the cervical spine is vital.

Evaluation and Rehabilitation after Adult Lumbar Spine Surgery.

Purpose: With an increase in the proportion of elderly patients, the global burden of spinal disease is on the rise. This is gradually expected to increase the number of surgical procedures all over the world in the near future. As we know, rehabilitation following spine surgery is critical for optimal recovery. However, the current literature lacks consensus regarding the appropriate post-operative rehabilitation protocol. The purpose of this review is to evaluate the optimal protocol for rehabilitation after lumbar spine surgery in adults. Materials and Methods: The goals of rehabilitation after lumbar spine surgery are to improve physical and psychosocial function and may include multiple modalities such as physical therapy, cognitive behavioral therapy, specialized instruments, and instructions to be followed during activities of daily living. In recent years, not only are a greater number of spine surgeries being performed, but various different techniques of lumbar spine surgery and spinal fusion have also emerged. (1) Our review summarizes post-operative rehabilitation under the following headings-1. Historical aspects, 2. Subjective functional outcomes, and (3) Actual rehabilitation measures, including balance. Results: Physical therapy programs need to be patient-specific and surgery-specific, such that they consider patient-reported outcome measures and take into consideration the technique of spinal fusion used and the muscle groups involved in these surgeries. By doing so, it is possible to assess the level of functional impairment and then specifically target the strengthening of those muscle groups affected by surgery whilst also improving impaired balance and allowing a return to daily activities. Conclusions: Rehabilitation is a multi-faceted journey to restore mobility, function, and quality of life. The current rehabilitation practice focuses on muscle strengthening, but the importance of spinal balance is less elaborated. We thus equally emphasize muscle strengthening and balance improvement post-lumbar spine surgery.

Use of a Triaxial Accelerometer to Measure Changes in Gait Sway and Related Motor Function after Corrective Spinal Fusion Surgery for Adult Spinal Deformity.

Background: Adult spinal deformity is a complex condition that causes lower back pain, causing spinal imbalance and discomfort in activities of daily life. After corrective spinal surgery, patients' gait and balance abilities might not revert to normalcy and they might be at increased risk of falling. Therefore, early evaluation of such a risk is imperative to prevent further complications such as a fall, or even worse, fractures in post-surgery ASD patients. However, there has been no report of an investigation of such early changes in gait sway before and after ASD surgery. This is a prospective to investigate changes in gait sway before and following ASD surgery, using accelerometers, and also to examine motor function related to postoperative gait sway. Methods: Twenty patients were included who underwent corrective surgery as treatment for ASD, from October 2019 to January 2023. Measurement parameters included a 10 m walking test and the timed up-and-go test (TUG), gait sway was evaluated using accelerometers (root mean square; RMS), and hip flexion and knee extension muscle strength were tested. RMS included RMS vertical: RMSV; RMS anterior posterior: RMSAP; RMS medial lateral: RMSML. The radiographic spinopelvic parameters were also evaluated preoperatively and postoperatively. p < 0.05 was noted as remarkably significant. Results: Preoperative and postoperative RMSV were 1.07 ± 0.6 and 1.31 ± 0.8, respectively (p < 0.05). RMSML significantly decreased from 0.33 ± 0.2 to 0.19 ± 0.1 postoperatively (p < 0.01). However, RMSAP did not change postoperatively (0.20 ± 0.2 vs. 0.14 ± 0.1, p > 0.05). Patients' one-month postoperative hip flexor muscle strength became significantly weaker (0.16 ± 0.04 vs. 0.10 ± 0.03 kgf/kg, p = 0.002), but TUG was maintained (11.6 ± 4.2 vs. 11.7 s, p = 0.305). RMSV was negatively correlated with quadriceps muscle strength and positively with TUG. RMSAP was negatively correlated with quadriceps muscle strength. All spinopelvic parameters became normal range after surgery. Conclusions: After corrective spinal fusion for ASD patients, the gait pattern improved significantly. Iliopsoas (hip flexor) and quadriceps femoris (knee extensor) muscles may play important roles for gait anterolateral and vertical swing, respectively.

Identification of kynurenine and quinolinic acid as promising serum biomarkers for drug-induced interstitial lung diseases.

BACKGROUND: Drug-induced interstitial lung disease (DILD) is a lung injury caused by various types of drugs and is a serious problem in both clinical practice and drug development. Clinical management of the condition would be improved if there were DILD-specific biomarkers available; this study aimed to meet that need. METHODS: Biomarker candidates were identified by non-targeted metabolomics focusing on hydrophilic molecules, and further validated by targeted approaches using the serum of acute DILD patients, DILD recovery patients, DILD-tolerant patients, patients with other related lung diseases, and healthy controls. RESULTS: Serum levels of kynurenine and quinolinic acid (and kynurenine/tryptophan ratio) were elevated significantly and specifically in acute DILD patients. The diagnostic potentials of these biomarkers were superior to those of conventional lung injury biomarkers, Krebs von den Lungen-6 and surfactant protein-D, in discriminating between acute DILD patients and patients with other lung diseases, including idiopathic interstitial pneumonia and lung diseases associated with connective tissue diseases. In addition to identifying and evaluating the biomarkers, our data showed that kynurenine/tryptophan ratios (an indicator of kynurenine pathway activation) were positively correlated with serum C-reactive protein concentrations in patients with DILD, suggesting the potential association between the generation of these biomarkers and inflammation. Our in vitro experiments demonstrated that macrophage differentiation and inflammatory stimulations typified by interferon gamma could activate the kynurenine pathway, resulting in enhanced kynurenine levels in the extracellular space in macrophage-like cell lines or lung endothelial cells. Extracellular quinolinic acid levels were elevated only in macrophage-like cells but not endothelial cells owing to the lower expression levels of metabolic enzymes converting kynurenine to quinolinic acid. These findings provide clues about the molecular mechanisms behind their specific elevation in the serum of acute DILD patients. CONCLUSIONS: The serum concentrations of kynurenine and quinolinic acid as well as kynurenine/tryptophan ratios are promising and specific biomarkers for detecting and monitoring DILD and its recovery, which could facilitate accurate decisions for appropriate clinical management of patients with DILD.

Minimal Clinically Important Differences in Gait and Balance Ability in Patients Who Underwent Corrective Long Spinal Fusion for Adult Spinal Deformity.

STUDY DESIGN: Retrospective observational study. BACKGROUND: The risk of a femoral neck fracture due to a fall after adult spinal deformity surgery has been reported. One of the most significant factors among walking and balance tests in post-operative ASD patients was the timed up-and-go test (TUG). This study aims to calculate the minimal clinically important difference (MCID) in balance tests after ASD surgery. METHODS: Forty-eight patients, 4 males and 44 females, were included by exclusion criteria in 66 consecutive patients who underwent corrective surgery as a treatment for ASD at our institution from June 2017 to February 2022. The inclusion criteria for this study were age ≥50 years; and no history of high-energy trauma. The exclusion criteria were dementia, severe deformity of the lower extremities, severe knee or hip osteoarthritis, history of central nervous system disorders, cancer, and motor severe paralysis leading to gait disorders. The surgeries were performed in two stages, first, the oblique lumber interbody fusion (OLIF) L1 to L5 (or S1), and second, the posterior corrective fusion basically from T10 to pelvis. For outcome assessment, 10 m walk velocity, TUG, ODI, and spinopelvic parameters were used. RESULTS: Ten meter walk velocity of pre-operation and post-operation were 1.0 ± 0.3 m/s and 1.2 ± 0.2 m/s, respectively (p < 0.01). The TUG of pre-operation and post-operation were 12.1 ± 3.7 s and 9.7 ± 2.2 s, respectively (p < 0.01). The ODI improved from 38.6 ± 12.8% to 24.2 ± 15.9% after surgery (p < 0.01). All post-operative parameters except PI obtained statistically significant improvement after surgery. CONCLUSIONS: This is the first report of MCID of the 10 m walk velocity and TUG after ASD surgery. Ten meter walk velocity and the TUG improved after surgery; their improvement values were correlated with the ODI. MCID using the anchor-based approach for 10 m walk velocity and the TUG were 0.10 m/s and 2.0 s, respectively. These MCID values may be useful for rehabilitation after ASD surgery.

Stratifin as a novel diagnostic biomarker in serum for diffuse alveolar damage.

Among the various histopathological patterns of drug-induced interstitial lung disease (DILD), diffuse alveolar damage (DAD) is associated with poor prognosis. However, there is no reliable biomarker for its accurate diagnosis. Here, we show stratifin/14-3-3σ (SFN) as a biomarker candidate found in a proteomic analysis. The study includes two independent cohorts (including totally 26 patients with DAD) and controls (total 432 samples). SFN is specifically elevated in DILD patients with DAD, and is superior to the known biomarkers, KL-6 and SP-D, in discrimination of DILD patients with DAD from patients with other DILD patterns or other lung diseases. SFN is also increased in serum from patients with idiopathic DAD, and in lung tissues and bronchoalveolar lavage fluid of patients with DAD. In vitro analysis using cultured lung epithelial cells suggests that extracellular release of SFN occurs via p53-dependent apoptosis. We conclude that serum SFN is a promising biomarker for DAD diagnosis.

The Most Significant Factor Affecting Gait and Postural Balance in Patients' Activities of Daily Living Following Corrective Surgery for Deformity of the Adult Spine.

Background and Objectives: Gait ability and spinal postural balance affect ADL in patients who underwent adult spinal deformity (ASD) surgery. However, it is still unclear how to determine what the cause is. This study was done to investigate various factors affecting gait, postural balance and activities of daily living (ADL) in patients who were operated on for ASD over a period of one year, following corrective surgery. Materials and Method: A cohort of 42 (2 men, 40 women, mean age, 71.1 years) who were operated on for ASD were included in this study. According to Oswestry Disability Index (ODI), based on their ADL, patients were segregated into satisfied and unsatisfied groups. Gait and postural balance abilities were evaluated before and after the operative procedure. Radiographs of spine and pelvis as well as the rehabilitation data (static balance, standing on single-leg; dynamic postural adaptation, timed up and go test (TUG); Gait Capability, walk velocity for a distance of 10 m) were acquired 12 months after surgery and analyzed. Spinopelvic parameters such as (lumbar lordosis (LL), pelvic tilt (PT), sagittal vertical axis (SVA), pelvic incidence (PI)) were marked and noted. The factors which affect patients' satisfaction with their ADL were evaluated. Results: The ADL satisfied group included 18 patients (1 man, 17 women, mean age 68.6 years) and the unsatisfied group included 24 patients (1 man, 23 women, mean age 73.1 years). One year after the surgery, the two groups were tested. TUG (8.5 s vs. 12.8 s), 10 m walk velocity (1.26 m/s vs. 1.01 m/s), and single leg standing test (25 s vs. 12.8 s) were regarded as notably different. According to logistic regression analysis, only TUG was extracted as a significant factor. The cut-off value was 9.7 s, with sensitivity 75%, specificity 83%, area under the curve 0.824, and a 95% confidence interval of 0.695-0.953. Conclusions: A significant factor among all evaluations in postoperative ASD patients was TUG, for which the cut-off value for ADL satisfaction was 9.7 s.

Progression process and safety assessment adaptation of endometrial lesions in ENU-induced 2-stage uterine carcinogenicity in a Tg-rasH2 mouse model.

Although acotiamide hydrochloride hydrate (acotiamide-HH) has not been reported to have genotoxic findings in any of the genotoxicity studies or treatment-related toxicological findings in reproductive and developmental studies, suspicious uterine tumorigenesis was observed in the results of a long-term rat carcinogenicity study. To clarify the uterine tumorigenesis of acotiamide-HH, we performed a 2-stage uterine carcinogenicity model in the transgenic rasH2 mouse initiated by N-Ethyl-N-nitrosourea (ENU). This model facilitated the short-term detection of uterine carcinogenic potential, and it appears to be a very useful testing method for assessing the safety of chemicals that may affect uterine tumorigenesis. However, there have not been many reports on this model, and accumulation of case studies using this model is recommended to support its usability. In this study, we performed this carcinogenesis model to not only confirm uterine tumorigenesis of acotiamide-HH but also to confirm the reliability of the model. The results of this study revealed that the endometrial adenocarcinoma found in the long-term rat carcinogenicity study possibly arose spontaneously. Also, we confirmed early induction of a uterine tumor as in previous reports and confirmed that 26 weeks is the appropriate treatment period for this rasH2 mouse model according to time-course observations of uterine tumor development.

Effects of four-week feed restriction on toxicological parameters in beagle dogs.

This study was conducted to examine any changes caused by feed restriction in dogs to contribute to safety evaluation in toxicity studies. Two male 7-month-old beagle dogs/group were fed 300 (control), 150 (50% of control), or 70 g/animal of diet daily (23% of control) for 4 weeks. Effects of feed restriction, except for clinical signs, were noted depending on the feed dosage in almost all examinations. The principal outcomes were: decreased body weight and water consumption, ECG changes (decreased heart rate and prolonged QTc), and hematopoietic and lymphopoietic suppression (decreased reticulocyte ratio or white blood cell count in hematology, decreased nucleated cell count in bone marrow, decreased erythroid parameters in myelography, and hypocellularity of bone marrow and thymic atrophy in histopathology). In addition, some changes were noted in urinalysis (decreased urine volume and sodium and potassium excretion), blood chemistry (decreased ALP and inorganic phosphorus and increased creatinine), organ weights, and gastric histopathology. These results provide important reference data for distinguishing the primary effects of test compounds from secondary effects of decreased food consumption in toxicity studies in beagle dogs.

Simultaneous expression of cancer stem cell-like properties and cancer-associated fibroblast-like properties in a primary culture of breast cancer cells.

The importance of cancer-associated fibroblasts (CAFs) in cancer biology has been recently highlighted owing to their critical roles in cancer growth, progression, metastasis, and therapeutic resistance. We have previously established a primary culture of breast cancer cells, which showed epithelial-mesenchymal transition and cancer stem cell-like properties. In this study, we found that the primary culture also showed CAF-like properties. For example, hypoxia inducible factor 1α (HIF1A) and its downstream genes, nuclear factor-kappa B2 (NF-κB2) and BCL2/adenovirus E1B 19 kd-interacting protein 3 (BNIP3), and many enzymes involved in glycolysis, such as GAPDH, LDH, PGAM1, and PKM2, were highly overexpressed in the primary culture. Moreover, media conditioned with the primary culture cells enhanced the growth of breast cancer cells. Similar to previous CAF studies, this enhancement suggested to be occurred through fibroblast growth factor signaling. This MCKH primary culture cell, which showed simultaneous expression of tumorigenic and CAF properties, offers a unique experimental system for studying the biology of CAFs.

Primary culture of breast cancer: a model system for epithelial-mesenchymal transition and cancer stem cells.

BACKGROUND: A novel model system to study the cellular, molecular, and genetic characteristics of breast cancer stem cells is needed. Personalized prognostic models are indispensable for assessing the effect of so-called tailor-made adjuvant therapy. MATERIALS AND METHODS: Surgically-extirpated tissues were dispersed with Dispase and cultured in commonly used medium. The expression of tumor markers was detected with immunohistochemistry, and gene expression profiles of tissues and cells were analyzed using the Agilent Human Microarray. RESULTS: We established a primary culture, which exhibited mesenchymal morphology. The gene expression profile of the primary culture revealed that the cells underwent epithelial-mesenchymal transition and had cancer stem cell properties. CONCLUSION: A primary culture of breast cancer cells can be easily established and could be used for studying breast cancer stem cells and assessing treatment of a patient.