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Patient-derived tumour organoids (PDOs) have revolutionised our understanding of cancer biology and the applications of personalised therapies. These advancements are principally ascribed to the ability of PDOs to consistently recapitulate and maintain the genomic, proteomic and morphological characteristics of parental tumours. Given these characteristics, PDOs (and their extended biobanks) are a representative preclinical model eminently suited to translate relevant scientific findings into personalized therapies rapidly. Here, we summarise recent advancements in PDOs from the perspective of cancer biology and clinical applications, focusing on the current challenges and opportunities of reconstructing and standardising more sophisticated PDO models. STATEMENT OF SIGNIFICANCE: Patient-derived tumour organoids (PDOs), three-dimensional (3D) self-assembled organotypic structures, have revolutionised our understanding of cancer biology and the applications of personalised therapies. These advancements are principally ascribed to the ability of PDOs to consistently recapitulate and maintain the genomic, proteomic and morphological characteristics of parental tumours. Given these characteristics, PDOs (and their extended biobanks) are a representative preclinical model eminently suited to translate relevant scientific findings into personalized therapies rapidly.

To retrospectively evaluate the clinical efficacy and safety of percutaneous kyphoplasty (PKP) for the management of osteoblastic-related metastatic vertebral lesions.A total of 31 patients with 58 osteoblastic-related metastatic vertebral lesions underwent PKP were reviewed. The clinical efficacy was assessed based on parameters including visual analogue scale, Oswestry Disability Index, vertebral body height variation and quality of life. Major and minor complications were systematically evaluated to assess the safety of the procedure.Average follow-up period was 22.5 ± 11.1 months(range, 3 to 46 months). The procedure duration time ranged from 50 to 180 minutes (average 96.8 ± 36.9 minutes). Mean visual analogue scale scores decreased significantly from 6.1 ± 1.8 pre-operatively to 2.7 ± 1.5 at 3 days after PKP (p0.001), and remained largely immutable at 1 month (2.0 ± 0.7; 31 patients; p0.001), 3 months (2.4 ± 1.2; 30 patients; p0.001) and 1 year (3.0 ± 1.0; 27 patients; p0.001). Oswestry Disability Index scores and vertebral body height variation also changed after the procedure, with significant differences between pre-operative scores and at each follow-up examination (p0.001). Mean quality of life scores were 90.8 ± 12.9 pre-operatively and improved to 99.5 ± 12.1(27 patients, p0.001) at 1 year after PKP. The only minor encountered complication was bone cement leakage, which was seen in 6.5%(2 of 31) of patients. None of the patients experienced major complications.PKP is a safe and effective treatment strategy for osteoblastic-related metastatic vertebral lesions from a variety of tumor etiologies.

To compare the clinical and radiographic results of bipedicular and unipedicular approaches(UPK and BPK) in the management of metastatic vertebral lesions MATERIALS AND METHODS: Eighty-two patients with 159 metastatic vertebral lesions who underwent UPK(25 cases, 69 lesions) or BPK(57 cases, 90 lesions) were retrospectively evaluated. Clinical results were assessed mainly depending on the Visual Analogue Scale(VAS) score, Oswestry Disability Index(ODI) and Quality of Life(QoL). Radiographic outcomes were evaluated primarily on the basis of bone cement distribution and changes in vertebral body height(VBH). Major and minor complications were systematically evaluated and compared to assess the safety of the 2 procedures.No statistically significant differences were observed in age, sex, types of lesions, location of lesions, posterior vertebral body and/or pedicle involvement, percentage of vertebra invasion between the groups(p=0.17-0.83). The radiographic parameter VBH was similarly improved in both groups(p=0.26-0.93). There was a significant improvement in the clinical parameters VAS score, ODI, and QoL at each follow-up examination compared with the preoperative results(p0.001). Significant improvement was observed in the VBH at each follow-up point(p0.05) compared to pre-procedure. UPK was superior to BPK in terms of the operative duration(p0.001), cement volume(p=0.004), and surgical complications(p=0.04).Both UPK and BPK resulted in similar clinical and radiographic outcomes in patients with metastatic vertebral lesions. The UPK had advantages including a shorter operation and lower cement volume than the BPK, which may have played an important role in reducing the incidence of complications. UPK can replace BPK in the treatment of metastatic vertebral lesions.

Background To explore the clinical safety and efficacy of single-stage posterior-only debridement, decompression, allograft bone using titanium mesh and interbody fusion combined for the treatment of thoracolumbar spinal tuberculosis complicated with psoas abscesses. Methods A total of 38 patients diagnosed with thoracolumbar spinal tuberculosis complicated with psoas abscesses underwent surgery via single-stage posterior-only debridement, decompression, allograft bone using titanium mesh and interbody fusion from January 2010 to September 2016 were enrolled in the study. The clinical efficacy of the approach was assessed based on parameters including operating time, blood loss, Cobb angle, visual analogue scale (VAS) scores, Frankel grade, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Results The surgery duration was 224.4 ± 71.1 min with a blood loss of 731.8 ± 585.8 ml. The Cobb angle was corrected from 16.0 ± 15.4° preoperatively to 8.1 ± 7.4° postoperatively (P Conclusion Single-stage posterior-only debridement, decompression, allograft bone using titanium mesh and interbody fusion is a safe and effective approach for the management of thoracolumbar spinal tuberculosis complicated with psoas abscesses.

Antituberculosis chemotherapy have been widely used for lower cervical spine tuberculosis and brought out favorable outcomes. However, the contribution of surgical treatment is not well investigated yet. Therefore, this study aimed to evaluate the clinical efficacy and feasibility of surgical treatment for lower cervical spine tuberculosis by anterior debridement, decompression, fusion and instrumentation.From April 2011 to July 2016, 17 patients (9 males and 8 females, average age, 45.7 ± 16.8 years) with lower cervical spine tuberculosis (C4-C7) underwent anterior debridement, decompression, fusion and instrumentation. Frankel grading and visual analogue scale were used to assess neurological function and neck pain, respectively. Operating time, blood loss, erythrocyte sedimentation rate, C-reactive protein, kyphosis angle and postoperative complications were used to evaluate the clinical outcomes of surgery.The surgery duration time range from 78 to 322 min (average 136.2 ± 61.1 min) and the blood loss range from 50 to 500 ml (average 127.7 ± 110.9 ml). Kyphosis angle was 10.8 ± 11.8°on average preoperative and returned to -6.3 ± 10.4° postoperative (P 0.001, t = 12.3) and remained -4.4 ± 9.9°at final follow-up (P 0.001, t = 11.8). The average preoperative and final follow-up visual analogue scale scores were 4.6 ± 1.3 and 0.6 ± 0.5 respectively (P 0.001, t = 13.5). The erythrocyte sedimentation rate and C-reactive protein decreased gradually postoperative and returned to normal at final follow-up. No postoperative severe complications and no recurrence of tuberculosis occurred in all cases and neurologic function was improved in various degrees.Anterior debridement, decompression, fusion and instrumentation could serve as an effective treatment in the management of the lower cervical spine tuberculosis.

Patients with Hirayama disease (HD) present with a larger range of neck flexion and show signs of cervical spine instability. Cervical spine stability largely relies on cervical spine muscles. The purpose of this study was to compare the cross-sectional areas (CSAs) of cervical spine muscles between patients with HD and healthy controls, providing some insights into whether there is cervical spine muscle weakness and incongruence in HD patients. In this retrospective study, cervical spine muscles CSAs of 44 HD patients, as well as that of 44 age- and sex-matched healthy counterparts, were measured on the T2-weighted axial MR images. The ratios of cervical spine muscles CSA to the corresponding vertebral body areas, defined as R-CSAs, and the flexor/extensor CSA ratios were computed and compared between two groups. Compared with healthy counterparts, R-CSAs of total cervical spine muscles, total extensors, superficial extensors, and deep flexors were significantly lower in HD patients. HD patients also demonstrated a significantly greater superficial flexor/superficial extensor CSA ratio than the healthy counterparts, indicating a mismatch between superficial flexors CSA and superficial extensors CSA in HD patients. In this pioneering study, HD patients had decreased size in most cervical spine muscles and a mismatch between CSAs of superficial flexor and that of superficial extensors. These results indicate generalized weakness and incongruence of cervical spine muscles, which may predispose cervical spine of HD patients to a less stable situation. These slides can be retrieved under Electronic Supplementary Material.

Cyclin-dependent kinase 12 (CDK12), a transcription-related cyclin dependent kinase (CDK), plays a momentous part in multitudinous biological functions, such as replication, transcription initiation to elongation and termination, precursor mRNA (pre-mRNA) splicing, intron polyadenylation (IPA), and translation. CDK12 can act as a tumour suppressor or oncogene in disparate cellular environments, and its dysregulation likely provokes tumorigenesis. A comprehensive understanding of CDK12 will tremendously facilitate the exploitation of novel tactics for the treatment and precaution of cancer. Currently, CDK12 inhibitors are nonspecific and nonselective, which profoundly hinders the pharmacological target validation and drug exploitation process. Herein, we summarize the newly comprehension of the biological functions of CDK12 with a focus on recently emerged advancements of CDK12-associated therapeutic approaches in cancers.

We aimed to investigate the clinical outcomes of percutaneous kyphoplasty (PKP) for spinal metastases in older adult patients with comorbidities.Ninety-two older adults (age ≥ 60 years) with spinal metastases who underwent 148 PKP procedures were retrospectively analyzed. Tokuhashi scores, Tomita scores, age-adjusted Charlson Comorbidity Index (aCCI) scores, and American Society of Anesthesiologists (ASA) scores were evaluated before the procedure. The visual analog scale (VAS), Oswestry Disability Index (ODI), vertebral body height (VBH), and quality of life (QoL) were used to assess the efficacy of the procedure. Clinical safety was evaluated based on periprocedural complications.Tokuhashi scores and Tomita scores were 7.3 ± 4.0 and 5.8 ± 2.1, respectively. Excluding cancer-related factors, twelve patients (13.0%) had aCCI scores ≥4. Forty-three patients (46.7%) had ASA status ≥ III. Compared to preoperative status, average VAS scores, ODI scores, VBH variation, and QoL scores significantly improved at each follow-up examination point after PKP (p 0.001). No major complications occurred, nor was there decompensation of comorbidities in the perioperative period. Seventeen segments (11.5%) of twelve patients (13.0%) suffered bone cement leakage. Among them, one patient suffered intercostal neuralgia cured by steroid injection, and the other patient suffered hyperesthesia, which disappeared after taking gabapentin (0.3 g, bid) for five weeks. Another minor complication of local hematoma occurred in one patient, which spontaneously resolved without surgical intervention.PKP serves as a safe approach to provide significant pain relief, vertebral body height restoration, and QoL improvements for spinal metastases in older adults, independent of underlying disease.

The dissimilarity is a major problem in clinical therapy of skin cutaneous melanoma (SKCM). Objective and reproducible classification systems may help decode SKCM heterogeneity. ConsensusClusterPlus was used to establish a stable immune molecular classification based on ferroptosis-related genes that had been acquired from FerrDb. Moreover, the prognosis, somatic mutations, immune microenvironment characteristics, functional enrichment, and clinical responsiveness to the immune checkpoint blockade of different subtypes in two independent melanin datasets were compared. Kaplan-Meier curves, univariate, multivariate, least absolute contraction, and selection operator (LASSO) Cox regression analysis were used to develop a molecular model for predicting survival, which was verified by a nomogram on the basis of independent prognostic indicators. Two molecular subtypes (C1 and C2) for SKCM were first identified according to ferroptosis-related genes; C1 showed a poor prognosis, with lower infiltration degree of immune cells and TIED score and higher homologous recombination defects, fraction altered, the number of segments, and copy number amplification and deletion. These characteristics of C2 were the opposite of C1. A ferroptosis-related prognosis risk score (FPRS) model was constructed using 6 of 463 genes with differential expression between C1 and C2. This model splits patients into low- and high-risk cohorts. There were significant differences in the infiltration and proportion of immune cells, immune checkpoint gene expression, responsiveness to immune checkpoint therapy, and sensitivity to chemotherapeutic medications between low- and high-risk cohorts. This model was an independent prognostic marker for SKCM and has a high AUC. In summary, we have identified two subtypes of SKCM with different molecular and immune characteristics on the basis of ferroptosis-related genes and further developed and verified an FPRS model, which might independently serve as a prognostic marker for SKCM.

ObjectiveTo retrospectively compare the clinical efficacy and safety of percutaneous kyphoplasty (PKP) for the management of osteolytic and osteoblastic-related metastatic vertebral lesions.MethodsA total of 117 patients with osteolytic (87 cases, 159 lesions, OL group) or osteoblastic-related (30 cases, 56 lesions, OB group) metastatic vertebral lesions underwent PKP. The clinical efficacy was assessed based on parameters including Visual Analog Scale (VAS), Oswestry Disability Index (ODI), vertebral body height (VBH) variation, and quality of life (QoL). Major and minor complications were systematically evaluated to assess the safety of the procedure.ResultsNo significant differences were found in the age, sex, or amount of bone cement between both groups (p>0.05). Compared with the OB group, the OL group was superior in operation duration (p0.05). The incidence of complications in the OL group was significantly higher than that in the OB group (pConclusionsPKP can safely achieve pain relief, functional improvement, VBH restoration, and QoL improvement for patients with osteolytic or osteoblastic-related metastatic vertebral lesions. Patients with osteolytic metastatic vertebral lesions showed better VBH restoration and had a shorter operation time but experienced less pain relief and had a greater incidence of complications than patients with osteoblastic-related metastatic vertebral lesions after PKP.

Background Hirayama disease (HD), characterized by insidiously progressive muscular atrophy of forearms and hands, is a self-limited cervical myelopathy that predominantly affects male adolescents, with female patients, especially middle-aged women, rarely affected. We present a rare case of HD with severe spinal cord injury in a 34-year-old woman. Case Description A 34-year-old woman presented with progressive weakness of both hands and forearms for a duration of 6 years and spastic gait for 1 year. The patient worked as a teacher and experienced long-term and repetitive neck flexion while writing at a desk, potentially causing cervical loading. Examination showed weakness and muscular atrophy of the bilateral upper limbs and pyramidal signs, including Hoffmann sign and hyperreflexia of the lower limbs. Radiologic studies revealed midcervical kyphosis and spinal cord compression by forward displacement of the dura mater with neck flexion. The clinical presentation and radiologic characteristics confirmed the diagnosis of HD. Anterior cervical corpectomy and fusion was performed owing to severe spinal cord injury, and the patient experienced satisfactory improvement. Conclusions The present case clarified the potential involvement of cervical kyphosis and cervical loading–related exercise in the onset and progression of HD. Anterior cervical corpectomy and fusion could serve as a promising treatment of HD with severe spinal cord injury.

To evaluate the clinical efficacy and feasibility of one-stage surgical treatment for consecutive multisegment thoracic spinal tuberculosis with kyphosis by posterior-only debridement, interbody fusion, and instrumentation.Sixty-two patients who underwent posterior debridement, interbody fusion, and instrumentation were reviewed for radiographic fusion, region kyphosis, neurologic status, and clinical outcomes. Thoracic Cobb's angle and Frankel grading system were used to assess kyphosis and neurologic improvements, respectively. Operation time, blood loss, erythrocyte sedimentation rate, C-reactive protein, visual analogue scale score, and postoperative complications were recorded to evaluate efficacy and feasibility.The surgery duration was 234.5 ± 91.3 minutes, with blood loss of 761.3 ± 598.5 mL. The levels of erythrocyte sedimentation rate and C-reactive protein in all patients decreased gradually to normal within 3 months after the surgery. Kyphosis angle was corrected from 16.9 ± 10.9° preoperatively to 10.4 ± 6.3° postoperatively (P0.001, t = 5.2) and remained at 12.0 ± 6.6° at final follow-up (P0.001, t = 4.6). Twenty-seven patients obtained neurologic improvement by 1-3 grades. The average visual analogue scale score decreased from preoperative 3.7 ± 1.0 to postoperative 0.7 ± 0.9 (P0.001, t = 16.4), and then to 0.5 ± 0.3 at final follow-up (P0.001, t = 21.5). All patients achieved bony fusion. Recurrence of tuberculosis was not found in all patients.One-stage posterior surgery of debridement, interbody fusion and instrumentation could serve as an efficient way to cure patients with consecutive multisegment thoracic spinal tuberculosis.

To investigate the effectiveness of allograft bones combined with poly-ether-ether-ketone (PEEK) cages or titanium mesh cages (TMCs) in the management of cervical spinal tuberculosis.A total of 16 patients with cervical spinal tuberculosis who underwent anterior debridement, reconstruction with allograft bones combined with PEEK cages or TMCs, and anterior plate fixation between 2013 and 2016 were retrospectively studied. Neck pain, neurologic status, operating time, intraoperative blood loss, cervical spine alignment, bony fusion, and self-reported clinical outcomes were reviewed.Six patients underwent 1 level reconstruction using PEEK cages and 10 patients received TMCs reconstruction. Patients received a mean follow-up time of 45.9 ± 13.1 months. Neck pain was greatly relieved, as visual analog scale scores decreased from 4.6 ± 1.3 preoperatively to 0.7 ± 0.5 at the final follow-up (P0.05). Neurologic status was improved in all patients with neurologic deficits, with 9 patients improving by 1 grade and 1 patient by 2 grades. Kyphosis angle was corrected from 1.3 ± 12.0 degrees preoperatively to -5.4 ± 10.2 degrees postoperatively (P0.05) and remained at -3.6 ± 9.6 degrees at the final follow-up (P0.05). Bony fusion was achieved in all patients, with a mean time to the fusion of 3.8 ± 1.3 months. There was no implant failure or signs of cervical spinal tuberculosis recurrence. Excellent results, good results, and fair results were reported in 37.5%, 56.25%, and 6.25% of patients, respectively.Allograft bone combined with PEEK cages and TMCs could bring about favorable clinical results in patients with cervical spinal tuberculosis. This method could be an alternative to autologous bone grafting method in the management of certain cases.

To provide a quantitative assessment of clinical outcomes of anterior cervical surgery for patients with Hirayama disease.Nineteen patients undergoing anterior cervical surgery were retrospectively collected, and preoperative and postoperative clinical and radiographic data were compared.All patients had a mean follow-up time of 72.5 ± 30.6 months. Tremor in 6 of 14 patients and cold paralysis in 8 patients were resolved after operation. Grip strength of upper extremities was significantly improved (preoperative 15.67 ± 2.74 kg vs. postoperative 19.82 ± 2.89 kg, P0.001). Postoperative cervical lordosis was significantly increased to 6.41 ± 4.39 mm from 2.70 ± 4.61 mm (P0.001). The overall range of cervical flexed motion was significantly decreased (preoperative 33.10° ± 10.60° vs. postoperative 13.55° ± 6.69°, P0.001), with segmental range of C5-6 (preoperative 12.52° ± 7.13° vs. postoperative 7.04° ± 3.75°, P = 0.002) and C6-7 (preoperative 9.01° ± 5.01° vs. postoperative 5.73° ± 2.74°, P = 0.014) contributing significantly to the improvement. Postoperative angle mobility of C3-4 to C6-7 was significantly decreased (P0.001). Postoperative neutral magnetic resonance imaging showed the transverse area of spinal cord of C6 (P = 0.016) and C7 (P = 0.021) was significantly increased.Anterior cervical surgery can provide clinical efficacy and imaging improvement, including reduced range of cervical flexed motion and angle mobility of lower cervical spine and increased cervical lordosis and spinal cord area.

Background: The study aimed to evaluate the clinical efficacy and safety of minimally invasive approach for painful spinal osteoblastic metastases by percutaneous kyphoplasty (PKP).Methods: A total of 30 patients (11 males and 19 females, average age, 58.9 ± 8.7 years) with 56 spinal osteoblastic lesions underwent PKP under conscious sedation were reviewed retrospectively. Visual analogue scale (VAS) score was employed to assess pain. Karnofsky performance score (KPS), quality of life (QOL) score (short form with 36 questions) and related complications were used to evaluate the clinical outcomes of the procedures.Results: All patients underwent PKP successfully and the pain was significantly alleviated after PKP. Mean VAS scores decreased significantly from 6.07 ± 1.84 preoperatively to 2.70 ± 1.56 at 3 days after PKP (PConclusions: As a minimally invasive surgery, PKP may not only effectively allevated the pain, but also safely improved the QOL of spinal osteoblastic metastatic patients.

Background: To explore the clinical safety and efficacy of single-stage posterior-only debridement, decompression, allograft bone using titanium mesh and interbody fusion combined for the treatment of thoracolumbar spinal tuberculosis complicated with psoas abscesses.Methods: A total of 38 patients diagnosed with thoracolumbar spinal tuberculosis complicated with psoas abscesses underwent surgery via single-stage posterior-only debridement, decompression, allograft bone using titanium mesh and interbody fusion from January 2010 to September 2016 were enrolled in the study. The clinical efficacy of the approach was assessed based on parameters including operating time, blood loss, Cobb angle, visual analogue scale (VAS) scores, Frankel grade, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP).Results: The surgery duration was 224.4 ± 71.1 min with a blood loss of 731.8 ± 585.8 ml. The Cobb angle was corrected from 16.0 ± 15.4° preoperatively to 8.1 ± 7.4° postoperatively (P < 0.001, t = -4.38), and returned to a level of 11.0 ± 8.5° at the final follow-up (P = 0.002, t = 3.38). Back pain was relieved, with the mean preoperative VAS of 3.5 ± 1.1 decreased to 0.7 ± 0.8 postoperatively (P < 0.001, t = 23.21) and then to 0.6 ± 0.5 at the final follow-up (P < 0.001, t = 17.07). Neurological function was improved in various degrees and psoas abscesses disappeared in all patients. The ESR and CRP decreased gradually after surgery and returned to normal at the final follow-up in all patients. All patients achieved bone fusion thoroughly and no recurrence of TB or surgical related complications was found at the final follow-up. Conclusion: Single-stage posterior-only debridement, decompression, allograft bone using titanium mesh and interbody fusion is a safe and effective approach for the management of thoracolumbar spinal tuberculosis complicated with psoas abscesses.

Objective: This study aimed to compare the effectiveness of titanium mesh cages (TMCs) with autogenous iliac bone grafts (AIBG) in posterior-only surgery for thoracic and lumbar spinal tuberculosis. Design: Retrospective investigative design. Setting: The First Affiliated Hospital of Fujian Medical University, Fuzhou, China. Participants: A total of 146 patients with thoracic or lumbar tuberculosis. Interventions: All patients underwent a posterior-only approach with either a TMC (86 cases) or AIBG (60 cases). Outcomes measures: Operation duration, intraoperative blood loss, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), visual analogue scale (VAS), and related complications were used to compare the effectiveness and feasibility of the two techniques. Frankel grading system, Cobb angle, and loss of angular correction were employed to assess neurological and kyphotic improvements. Results: There were significant improvements in ESR, CRP, VAS, Frankel grade, and Cobb angle at the last follow-up (P 0.05). A recurrence of tuberculosis was not found in either of the groups. Conclusion: Compared to autogenous iliac bone grafts, titanium mesh cages could serve as a superior material in posterior-only operative therapy for thoracic and lumbar spinal tuberculosis.

Objective To present a preliminary experience of perioperative management for patients with spinal tuberculosis (STB) and end-stage renal disease (ESRD) and discuss strategic factors that should be considered. Methods A retrospective study of 6 patients with STB and ESRD who underwent spine surgeries in our hospital from January 2010 to May 2017 was carried out. Medical records were reviewed for clinical manifestations, laboratory examinations, radiologic findings, perioperative management, clinical outcomes, and complications. Results Except for 1 patient who died of cardiac arrest 5 days after surgery, this case series was followed with a mean follow-up period of 17.0 months (range, 9–23). There were no patients reporting major side effects related to an adjusted antituberculosis chemotherapy regimen. Postoperatively, surgical incision healed primarily, whereas delirium and pneumonia were noted in 2 patients. At final follow-ups, solid bony fusion was achieved in 4 patients, whereas fusion was indefinite in the patient who underwent surgery at L3/4 level. Visual analogue scale score improved from preoperative 5.2 ± 0.37 to 2.6 ± 0.55 at the final follow-ups. Conclusions Perioperative management of patients with STB and ESRD is a complicated issue, with multiple factors to be considered. Spinal surgery can achieve acceptable outcomes in these patients if meticulous management is performed.