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Sigmoid diverticulitis can potentially lead to the development of pelvic abscesses. Mortality rate from intra-abdominal abscesses is as high as 35%, and patients with diverticulitis complicated by an abscess are at a high risk of recurrent diverticulitis. Recently, image-guided drainage has been performed using computed tomography or ultrasonography for the treatment of pelvic abscesses. Standard radiological pelvic abscess image-guided drainage methods consist of transabdominal, transgluteal, or cranio-caudal puncture approaches. However, these standard approaches have technical limitations due to intrapelvic organ structures. Therefore, we performed image-guided drainage using a percutaneous trans-bladder approach with a simpler 1-step puncture method and a less invasive 7-Fr drainage catheter in 2 cases of a 72-year-old female and a 53-year-old female with relapsed pelvic abscesses complicated by sigmoid diverticulitis due to difficulties involving the standard approach. The abscesses in both cases disappeared on follow-up computed tomography scans, demonstrating no pelvic abscess recurrence. Our results showed that trans-bladder image-guided drainage is an effective alternative method for treating pelvic abscesses.

Background: Cartilage harvest and transplantation is a common surgery using costal, auricular, and septal cartilage for craniofacial reconstruction. However, absorption and warping of the cartilage grafts can occur due to inflammatory factors associated with wound healing. Transcription factor nuclear factor-κB (NF-κB) is activated by the various stimulation such as interleukin-1 (IL-1), and plays a central role in the transactivation of this inflammatory cytokine gene. Inhibition of NF-κB may have anti-inflammatory effects. The aim of this study was to explore the potential of an NF-κB decoy oligodeoxynucleotide (Decoy) as a chondroprotective agent. Materials and Methods: Safe and efficacious concentrations of Decoy were assessed using rabbit nasal septal chondrocytes (rNSChs) and assays for cytotoxicity, proteoglycan (PG) synthesis, and PG turnover were carried out. The efficacious concentration of Decoy determined from the rNSChs was then applied to human nasal septal cartilage (hNSC) in vitro and analyzed for PG turnover, the levels of inflammatory markers, and catabolic enzymes in explant-conditioned culture medium. Results: Over the range of Decoy conditions and concentrations, no inhibition of PG synthesis or cytotoxicity was observed. Decoy at 10 μM effectively inhibited PG degradation in the hNSC explant, prolonging PG half-life by 63% and decreasing matrix metalloprotease 3 (MMP-3) by 70.7% (p = 0.027). Conclusions: Decoy may be considered a novel chondroprotective therapeutic agent in cartilage transplantation due to its ability to inhibit cartilage degradation due to inflammation cytokines.

Portosystemic shunts with cirrhosis may lead to hepatic encephalopathy (HE), which is often pharmacotherapy-resistant. We report a case of a 66-year-old female patient diagnosed with alcoholic cirrhosis and uncontrolled HE. She underwent percutaneous transhepatic obliteration (PTO) for treatment of a large portosystemic shunt from the left and right gastric veins to the azygos vein. We embolized the target veins using hydro-coated coils and filled them with n-butyl-2-cyanoacrylate (NBCA), leading to firmed obstruction of the large portosystemic shunt without NBCA migration, thus reducing the number of coils required. The HE symptoms improved after PTO and could thereafter be controlled with conservative therapy. Our results showed that PTO using an NBCA injection inside hydrogel-coated coils for a large portosystemic shunt associated with HE is effective and safe.

Abstract Background Endovascular therapy (ET) for delayed hepatic artery post-pancreatectomy hemorrhage (HA-PPH) may require complete hepatic artery occlusion (HAO). Nonetheless, the development of extrahepatic collateral circulation (EHC) and the relationship between radiological factors (EHC, portal vein stenosis, and HAO) and adverse hepatic events after ET remain unclear. This study aimed to evaluate the efficacy and safety of ET for delayed PPH and examine the development of EHC. Methods A total of 19 ET cases for delayed HA-PPH were reviewed. Hepatic adverse events, portal vein stenosis, HAO, and mortality rate after ET were evaluated. Moreover, EHC from the left gastric artery (LGA), right inferior phrenic artery (RIPA), left inferior phrenic artery (LIPA), right internal thoracic artery (RITA), left internal thoracic artery (LITA), renal artery (RA), omental artery (OA), intercostal artery (IA), and branch of superior mesenteric artery (BSMA) was assessed using angiogram and computed tomography angiography (CTA). Results All cases were successfully treated using transcatheter arterial embolization (n = 17) and stent-graft placement (n = 2) without mortality. EHC from the LGA (8/19), RIPA (10/19), LIPA (4/19), and RITA (3/19) was observed on post-ET CTA. The incidence of hepatic adverse events was significant in the group with both HAO and portal vein stenosis (p

Abstract Cancer patients are considered highly susceptible to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. However, it is not well known when chemotherapy can be safely restarted in cancer patients after coronavirus disease 2019 (COVID‐19). Here, we describe the case of an 18‐year‐old man diagnosed with primary mediastinal nonseminomatous germ cell tumor (PMNSGCT) in which chemotherapy could be safely restarted after COVID‐19. On day 11 of the third cycle of bleomycin, etoposide, plus cisplatin (BEP), he was diagnosed with mild COVID‐19. On day 16 after the onset of COVID‐19 (day 26 of third cycle of BEP), chemotherapy for his PMNSGCT was restarted. He received surgery after the fourth cycle of BEP without recurrence of COVID‐19. Chemotherapy could be restarted and followed by surgery in this post‐COVID‐19 patient who had experienced mild illness after the discharge criteria were met and all symptoms had disappeared. We report this case with a review of the literature on restarting chemotherapy after SARS‐CoV2 infection.

We investigated the effects of the cytokine inhibitors IL-1 receptor antagonist (IL-1Ra) and soluble tumor necrosis factor receptor-1 (sTNFR1) on the extracellular matrix metabolism of human intervertebral discs (IVDs) and the roles of IL-1β and TNF in the homeostasis of IVD cells. The 1.2% alginate beads and the explants obtained from 35 human lumbar discs were treated with cytokine inhibitors. Extracellular matrix metabolism was evaluated by proteoglycan (PG) and collagen syntheses and IL-1β, TNF, and IL-6 expressions after three days of culture in the presence or absence of IL-1Ra, sTNFR1, and cycloheximide. Simultaneous treatment with IL-1Ra and sTNFR1 stimulated PG and collagen syntheses in the NP and AF cells and explants. The IL-1β concentration was significantly correlated to the relative increase in PG synthesis in AF explants after simultaneous cytokine inhibitor treatment. The relative increase in PG synthesis induced by simultaneous cytokine treatment was significantly higher in an advanced grade of MRI. Expressions of IL-1β and TNF were upregulated by each cytokine inhibitor, and simultaneous treatment suppressed IL-1β and TNF productions. In conclusion, IL-1Ra and sTNFR1 have the potential to increase PG and collagen synthesis in IVDs. IL-1β and TNF have a feedback pathway to maintain optimal expression, resulting in the control of homeostasis in IVD explants.

Abstract Background Establishing an optimal animal model for intervertebral disc (IVD) degeneration is essential for developing new IVD therapies. The intra-articular injection of monosodium iodoacetate (MIA), which is commonly used in animal models of osteoarthritis, induces cartilage degeneration and progressive arthritis in a dose- and time-dependent manner. The purpose of this study was to determine the effect of MIA injections into rabbit IVDs on the progression of IVD degeneration evaluated by radiographic, micro-computerized tomography (micro-CT), magnetic resonance imaging (MRI), and histological analyses. Methods In total, 24 New Zealand White (NZW) rabbits were used in this study. Under general anesthesia, lumbar discs from L1–L2 to L4–L5 had a posterolateral percutaneous injection of MIA in contrast agent (CA) (L1–L2: CA only; L2–L3: MIA 0.01 mg; L3–L4: 0.1 mg; L4–L5: 1.0 mg; L5–L6: non-injection (NI) control). Disc height was radiographically monitored biweekly until 12 weeks after injection. Six rabbits were sacrificed at 2, 4, 8, and 12 weeks post-injection and processed for micro-CT, MRI (T2-mapping), and histological analyses. Three-dimensional (3D) disc height in five anatomical zones was evaluated by 3D reconstruction of micro-CT data. Results Disc height of MIA-injected discs (L2–L3 to L4–L5) gradually decreased time-dependently (P < 0.0001). The disc height of MIA 0.01 mg-injected discs was significantly higher than those of MIA 0.1 and 1.0 mg-injected discs (P < 0.01, respectively). 3D micro-CT analysis showed the dose- and time-dependent decrease of 3D disc height of MIA-injected discs predominantly in the posterior annulus fibrosus (AF) zone. MRI T2 values of MIA 0.1 and 1.0 mg-injected discs were significantly decreased compared to those of CA and/or NI controls (P < 0.05). Histological analyses showed progressive time- and dose-degenerative changes in the discs injected with MIA (P < 0.01). MIA induced cell death in the rabbit nucleus pulposus with a high percentage, while the percentage of cell clones was low. Conclusions The results of this study showed, for the first time, that the intradiscal injection of MIA induced degenerative changes of rabbit IVDs in a time- and dose-dependent manner. This study suggests that MIA injection into rabbit IVDs could be used as an animal model of IVD degeneration for developing future treatments.

Abstract Background Peripheral nerve damage can have debilitating consequences. Rabbit sciatic nerve transection models allow the effective evaluation of surgical repair strategies for large nerve gaps. Despite advantages in size, ease of handling, and functional utility, rabbits can suffer from a number of side effects that affect animal welfare and the quality of scientific inquiry. Such side-effects, which include pressure ulcers and traumatic damage to the foot, are primarily a consequence of insensitivity of the distal hindlimb following sciatic nerve injury. In this study, we present a number of methodologies for identifying, treating, and preventing unintended adverse effects in rabbit sciatic nerve injury models. Results First, we categorize pressure ulcers according to their severity and describe the deployment of a padded bandaging technique to enable ulcer healing. We also introduce a proactive bandaging approach to reduce the likelihood of pressure ulcer formation. Second, we define phenotypes that distinguish between foot injuries resulting from self-mutilation (autotomy) from those caused by incidental traumatic injury secondary to sensori-motor damage. Finally, we detail an effective strategy to reduce the usage of Elizabethan collars; through a gradual weaning protocol, their usefulness in preventing autotomy is retained, while their propensity to impede rabbit grooming and cause abrasion-injury to the neck region is minimized. Conclusions We suggest that application of these methods offer a practical and systematic approach to avoid adverse side effects associated with rabbit sciatic nerve damage, enabling improved animal welfare and scientific outcomes in a powerful nerve injury model.

Ultra-short echo time (UTE) MRI with post-processing is a promising technique in bone imaging that produces a similar contrast to computed tomography (CT). Here, we propose a 3D slab-selective ultrashort echo time (UTE) sequence together with image post-processing to image bone structures in the lumbar spine. We also explore the intermodality agreement between the UTE and CT images. The lumbar spines of two healthy volunteers were imaged with 3D UTE using five different resolutions to determine the best imaging protocol. Then, four patients with low back pain were imaged with both the 3D UTE sequence and CT to investigate agreement between the imaging methods. Two other patients with low back pain were then imaged with the 3D UTE sequence and clinical conventional T1-weighted and T2-weighted fast spin-echo (FSE) MRI sequences for qualitative comparison. The 3D UTE sequence together with post-processing showed high contrast images of bone and high intermodality agreement with CT images. In conclusion, post-processed slab-selective UTE imaging is a feasible approach for highlighting bone structures in the lumbar spine and demonstrates significant anatomical correlation with CT images.

Mediastinum hematoma is often caused by chest trauma, aortic dissection, and tumor. Spontaneous nontraumatic middle mediastinum hematoma is a rare and potentially life-threatening condition. Here, we report the case of a patient who was a 46-year-old experienced sudden chest pain with spontaneous middle mediastinum hematoma caused by rupture of the bilateral bronchial artery. We successfully treated the patient with transcatheter arterial embolization via the bilateral bronchial artery using N-butyl-2-cyanoacrylate.

Abstract Background The rabbit lumbar spine is a commonly utilized model for studying intervertebral disc degeneration and for the pre‐clinical evaluation of regenerative therapies. Histopathology is the foundation for which alterations to disc morphology and cellularity with degeneration, or following repair or treatment are assessed. Despite this, no standardized histology grading scale has yet been established for the spine field for any of the frequently utilized animal models. Aims The purpose of this study was to establish a new standardized scoring system to assess disc degeneration and regeneration in the rabbit model. Materials and Methods The scoring system was formulated following a review of the literature and a survey of spine researchers. Validation of the scoring system was carried out using images provided by 4 independent laboratories, which were graded by 12 independent graders of varying experience levels. Reliability testing was performed via the computation of intra‐class correlation coefficients (ICC) for each category and the total score. The scoring system was then further refined based on the results of the ICC analysis and discussions amongst the authors. Results The final general scoring system involves scoring 7 features (nucleus pulposus shape, area, cellularity and matrix condensation, annulus fibrosus/nucleus pulposus border appearance, annulus fibrosus morphology, and endplate sclerosis/thickening) on a 0 (healthy) to 2 (severe degeneration) scale. ICCs demonstrated overall moderate to good agreement across graders. An addendum to the main scoring system is also included for use in studies evaluating regenerative therapeutics, which involves scoring cell cloning and morphology within the nucleus pulposus and inner annulus fibrosus. Discussion Overall, this new scoring system provides an avenue to improve standardization, allow a more accurate comparison between labs and more robust evaluation of pathophysiology and regenerative treatments across the field. Conclusion This study developed a histopathology scoring system for degeneration and regeneration in the rabbit model based on reported practice in the literature, a survey of spine researchers, and validation testing.

Hepatic artery aneurysms are rare and sometimes life-threating. Various treatments for hepatic artery aneurysms, including surgical and endovascular techniques are present. Here, we report the case of a 68-year-old woman who presented with an about 9 cm of common hepatic artery aneurysm detected during a routine medical checkup; she did not exhibit any symptoms. We successfully treated the aneurysm with transcatheter arterial embolization with isolation technique via pancreatic duodenal arcade. Keywords: Common hepatic artery aneurysm, Transcatheter arterial embolization, Isolation technique via pancreaticoduodenal arcade

Abstract Background A solitary fibrous tumor (SFT) is a rare mesenchymal tumor that occurs mostly in pleural sites, and an SFT occurring in the ischiorectal fossa is extremely rare. Because of the rarity, there are few reports detailing an SFT in the ischiorectal fossa. Case presentation A pararectal tumor was incidentally found in a 42-year-old man during a routine medical examination. The patient had no symptoms and no previous medical history. In the physical examination, a smooth-margined and hard elastic mass was felt, and in a digital rectal examination, the rectal mucosa appeared normal. A computed tomography (CT) scan showed a 5-cm, well-defined, solid mass in the left ischiorectal fossa. Contrast-enhanced CT in the early phase showed intense heterogeneous enhancement that persisted during the delayed phase. T2-weighted images of magnetic resonance imaging yielded heterogeneous intermediate and low signal intensity. Intense arterial enhancement suggested a hypervascular nature, and persistent delayed enhancement and low signal bands on T2-weighted images suggested a fibrous component of the mass. An SFT was suspected. Most SFTs are benign but have malignant potential. Our patient did not hope for surgery if the tumor was benign; therefore, an ultrasound-guided transperineal core needle biopsy was performed to decide on a treatment strategy. Microscopic examination showed tumor cells appearing as spindle and fibroblast-like cells within a collagenous stroma. Immunohistochemistry identified CD34 and vimentin, supporting the diagnosis of an SFT. The patient consented to excision of the mass. He was placed in a prone jackknife position, and the tumor was removed transperineally using a posterior approach (modified Kraske procedure). The levator ani muscle, external sphincter muscles, and rectum were not involved and separated from the tumor. The tumor was successfully resected en bloc with no complications. Five uneventful days post surgery, the patient was discharged. There was no local recurrence during the year following surgery. Conclusion Imaging findings reflect the tissue characterization such as hypervascularity and fibrous nature of SFTs. We have presented a rare case of an SFT in the ischiorectal fossa with useful imaging findings for diagnosis, treatment strategy, and successful surgical removal using a posterior approach.

Sarcoidosis is a multisystemic inflammatory disease of unknown origin characterized by the formation of noncaseating granulomas and accumulation of inflammatory cells. Sarcoidosis most commonly affects the lungs and lymphoid system. However, the liver can also be involved in 50%-65% of cases. On magnetic resonance imaging, sarcoidosis lesions usually present as hypointense lesions on all sequences. However, we present a rare case of nodular liver sarcoidosis presenting with T2 hyperintense lesions. In addition, while most cases of hepatic nodular sarcoidosis present with multiple small hepatic nodules, liver masses of our case are larger than usual. Moreover, this case suggested that when intact vascular structures penetrating liver nodular lesions are observed as in the current case, liver sarcoidosis can be included in a list of differential diagnosis. Keywords: Hepatic sarcoidosis, Atypical manifestations, CT, MRI

Abstract Background The degeneration of the intervertebral disc (IVD) is characterized by proteolytic degradation of the extracellular matrix, and its repair requires the production of an extracellular matrix with a high proteoglycan-to-collagen ratio characteristic of a nucleus pulposus (NP)-like phenotype in vivo. At the moment, there is no medical treatment to reverse or even retard disc degeneration. The purpose of the present study was to determine if a low dose of short link N (sLN), a recently discovered fragment of the link N peptide, could behave in a manner similar to that of link N in restoring the proteoglycan content and proteoglycan-to-collagen ratio of the disc in a rabbit model of IVD degeneration, as an indication of its potential therapeutic benefit in reversing disc degeneration. Methods Adolescent New Zealand white rabbits received an annular puncture with an 18-gauge needle into two noncontiguous discs to induce disc degeneration. Two weeks later, either saline (10 μL) or sLN (25 μg in 10 μL saline) was injected into the center of the NP. The sLN concentration was empirically chosen at a lower molar concentration equivalent to half that of link N (100 μg in 10 μL). The effect on radiographic, biochemical and histologic changes were evaluated. Results Following needle puncture, disc height decreased by about 25–30% within 2 weeks and maintained this loss for the duration of the 12-week study; a single 25-μg sLN injection at 2 weeks partially restored this loss in disc height. sLN injection led to an increase in glycosaminoglycans (GAG) content 12 weeks post-injection in both the NP and annulus fibrosus (AF). There was a trend towards maintaining control disc collagen-content with sLN supplementation and the GAG-to-collagen ratio in the NP was increased when compared to the saline group. Conclusions When administered to the degenerative disc in vivo, sLN injection leads to an increase in proteoglycan content and a trend towards maintaining control disc collagen content in both the NP and AF. This is similar to link N when it is administered to the degenerative disc. Thus, pharmacologically, sLN supplementation could be a novel therapeutic approach for treating disc degeneration.

Abstract Background The progression of intervertebral disc (IVD) degeneration leads to rupture within IVD tissues. The location and appearance of areas of gaseous radiolucency in the IVD, known as vacuum phenomena (VPs), are considered to indirectly indicate the position and extent of IVD rupture. The clinical significance of VPs in degenerated IVDs is not fully understood. The purpose of this study is to assess and classify the morphology of IVD ruptures by the presence of intradiscal VPs, and to examine the association between morphological VP-positive IVD ruptures and degenerative lumbar diseases. Methods IVD rupture was evaluated by the presence of VPs using computed tomography (CT) imaging. VP shape (spot, linear, island) was classified using sagittal imaging, and VP distribution (A-N: anterior AF-NP; N: NP only; N-P: NP-posterior AF; A-N-P: anterior and posterior AF-NP) was classified using axial imaging. The disc height index (DHI) was calculated from lateral radiographs. Disc degeneration and lumbar spinal stenosis were evaluated by MRI grade. Results In the VP shape analysis, the island type was the most common, followed by linear and spot types. In the VP distribution analysis, A-N was the most common group, followed by N, N-P and A-N-P. Intra- and inter-observer reliabilities were statistically sufficient to classify different rupture shapes and distributions. The DHI tended to be lower in discs that contained VPs, especially in the anterior AF area. The shape and distribution of intradiscal VPs were significantly associated with the degree of disc degeneration and lumbar spinal stenosis graded by MRI. Discs with VPs extending from the NP into the anterior and/or posterior AF had a significantly higher proportion of advanced disc degeneration (Pfirrmann’s classification: grades IV and V). Conclusions This is the first study to analyze the morphology of IVD rupture evaluated by the presence of intradiscal VPs using CT imaging. This classification can comprehensively present the shape and axial distribution of VPs within IVDs. Intradiscal VPs are associated with the progression of disc degeneration and lumbar spinal stenosis.

Rupture of small intestinal varices associated with portal hypertension can be a serious condition that is difficult to diagnose early and to manage. Moreover, optimal guidelines for the treatment of small intestinal varices have not yet been established. We herein report a case of a 73-year-old man with small intestinal varices. The man presented with bleeding from a stoma in the small intestine, which subsequently led to hemorrhagic shock. We successfully treated the patient with balloon-occluded retrograde transvenous obliteration via the right inferior epigastric vein using N-butyl-2-cyanoacrylate. Keywords: Small intestinal varices, Balloon-occluded retrograde transvenous obliteration, N-butyl-2-cyanoacrylate

Barge-type platforms with moonpools are a promising type of foundation for floating offshore wind turbines due to their good seakeeping performance. In this paper, the mean wave drift force on a barge-type vertical-axis floating wind turbine with multiple moonpools was investigated through physical model testing and numerical calculations using WAMIT. The focus was on the characteristics of mean drift load and its optimization potential. The present numerical results indicated that the application of moonpools was useful in reducing horizontal mean drift force at specific frequencies, and the reason was ascribed to the significant radiation effect of the resonant water oscillations in moonpools. The observed reduction effect on mean drift force was shown to be dependent on the viscous damping of moonpool resonance. The experimental results showed that the maximum response of the mean sway drift force was reduced by the gyroscopic effect of rotations of the vertical-axis wind turbine, and this reduction effect became stronger as the rotating speed of the wind turbine increased, but was weakened as wave amplitude increased. The comparisons between experimental data and potential flow predictions indicated that viscous effects should be taken into account to reasonably estimate the mean wave drift forces on barge-type floating wind turbines.

Abstract Background The receptor activator of NF-κB ligand (RANKL), a member of the TNF ligand superfamily, is known to regulate bone metabolism. The expression of each component of the RANK/RANKL/osteoprotegerin (OPG) system in the intervertebral disc (IVD) has not been examined in detail. The purposes of this study were to examine the expression of the RANK/RANKL/OPG system and to evaluate the function of RANKL in the matrix metabolism of the rat IVD. Methods Sprague-Dawley, 12-week-old, male rats were used in this study. Anulus fibrosus (AF), nucleus pulposus (NP) and cartilaginous endplate (CEP) cells isolated from dissected thoracolumbar discs were monolayer-cultured. RANK/RANKL/OPG expression in rat IVDs was examined using real-time polymerase chain reaction (PCR) and immunohistochemical analysis (cultured cells and IVD tissues). To examine the effect of interleukin-1β (IL-1β) stimulation on the mRNA levels of RANK, RANKL and OPG, the cells were cultured with or without recombinant human IL-1β (rhIL-1β). To evaluate the effect of RANKL on the mRNA expression of catabolic factors (IL-1β, matrix metalloproteinase-3 (MMP-3) and MMP-13), the cells were cultured with RANKL in the presence or absence of rhIL-1β. The immunohistochemical expression of this system was also evaluated using human IVD tissues with different grades of degeneration. Results mRNA expression levels of RANK, RANKL, and OPG were clearly identified in AF, NP and CEP cells. Immunoreactivity to RANK, RANKL and OPG was distributed in the cell membranes and/or cytoplasm of the three types of cells. The mRNA level of RANKL was significantly upregulated by treatment with rhIL-1β of the three types of cells. Treatment with RANKL without rhIL-1β did not induce significant effects on the mRNA expression of catabolic factors by AF, NP and CEP cells. However, the expression was significantly upregulated by stimulation with RANKL in the presence of rhIL-1β. There was a general trend for more RANK/RANKL/OPG-positive cells in human IVD tissues in an advanced stage of degeneration compared to an early stage. Conclusions Our study showed the possibility that the RANK/RANKL/OPG system may play a part in the process of intervertebral disc degeneration.

Study DesignPreliminary clinical trial.PurposeTo determine the safety and initial efficacy of intradiscal injection of autologous platelet-rich plasma (PRP) releasate in patients with discogenic low back pain.Overview of LiteraturePRP, which is comprised of autologous growth factors and cytokines, has been widely used in the clinical setting for tissue regeneration and repair. PRP has been shown in vitro and in vivo to potentially stimulate intervertebral disc matrix metabolism.MethodsInclusion criteria for this study included chronic low back pain without leg pain for more than 3 months; one or more lumbar discs (L3/L4 to L5/S1) with evidence of degeneration, as indicated via magnetic resonance imaging (MRI); and at least one symptomatic disc, confirmed using standardized provocative discography. PRP releasate, isolated from clotted PRP, was injected into the center of the nucleus pulposus. Outcome measures included the use of a visual analog scale (VAS) and the Roland-Morris Disability Questionnaire (RDQ), as well as X-ray and MRI (T2-quantification).ResultsData were analyzed from 14 patients (8 men and 6 women; mean age, 33.8 years). The average follow-up period was 10 months. Following treatment, no patient experienced adverse events or significant narrowing of disc height. The mean pain scores before treatment (VAS, 7.5±1.3; RDQ, 12.6±4.1) were significantly decreased at one month, and this was generally sustained throughout the observation period (6 months after treatment: VAS, 3.2±2.4, RDQ; 3.6±4.5 and 12 months: VAS, 2.9±2.8; RDQ, 2.8±3.9; p

Objective: Bone metastasis occurs in up to 90% of men with advanced prostate cancer and leads to fractures, severe pain and therapy-resistance. Bone metastases induce a spectrum of types of bone lesions which can respond differently to therapy even within individual prostate cancer patients. Thus, the special environment of the bone makes the disease more complicated and incurable. A model in which bone lesions are reproducibly induced that mirrors the complexity seen in patients would be invaluable for pre-clinical testing of novel treatments. The microstructural changes in the femurs of mice implanted with PCSD1, a new patient-derived xenograft from a surgical prostate cancer bone metastasis specimen, were determined. Methods: Quantitative micro-computed tomography (micro-CT) and histological analyses were performed to evaluate the effects of direct injection of PCSD1 cells or media alone (Control) into the right femurs of Rag2−/−γc−/− male mice. Results: Bone lesions formed only in femurs of mice injected with PCSD1 cells. Bone volume (BV) was significantly decreased at the proximal and distal ends of the femurs (p

Abstract Introduction Estimation of intervertebral disc degeneration on magnetic resonance imaging (MRI) is challenging. Qualitative schemes used in clinical practice correlate poorly with pain and quantitative techniques have not entered widespread clinical use. Methods As part of a prior study, 25 New Zealand white rabbits underwent annular puncture to induce disc degeneration in 50 noncontiguous lumbar discs. At 16 weeks, the animals underwent multi‐echo T2 MRI scanning and were euthanized. The discs were stained and examined histologically. Quantitative T2 relaxation maps were prepared using the nonlinear least squares method. Decay Variance maps were created using a novel technique of aggregating the deviation in the intensity of each echo signal from the expected intensity based on the previous rate of decay. Results Decay Variance maps showed a clear and well demarcated nucleus pulposus with a consistent rate of decay (low Decay Variance) in healthy discs that showed progressively more variable decay (higher Decay Variance) with increasing degeneration. Decay Variance maps required significantly less time to generate (1.0 ± 0.0 second) compared with traditional T2 relaxometry maps (5 (±0.9) to 1788.9 (±116) seconds). Histology scores correlated strongly with Decay Variance scores (r = 0.82, P

Homeobox protein Mohwak (Mkx) is involved in tendon and ligament development. Here the authors show that Mkx in the outer annulus fibrosus of the intervertebral disc plays a role in maintenance of the IVD, showing that stem cells overexpressing Mkx enhance therapeutic IVD regeneration in mice.

Osteoporosis, characterized by increased fracture risk and bone fragility, impacts millions of adults worldwide, but effective, non-invasive and easily accessible diagnostic tests of the disease remain elusive. We present a magnetic resonance (MR) technique that overcomes the motion limitations of traditional MR imaging to acquire high-resolution frequency-domain data to characterize the texture of biological tissues. This technique does not involve obtaining full two-dimensional or three-dimensional images, but can probe scales down to the order of 40 μm and in particular uncover structural information in trabecular bone. Using micro-computed tomography data of vertebral trabecular bone, we computationally validate this MR technique by simulating MR measurements of a ‘ratio metric’ determined from a few k-space values corresponding to trabecular thickness and spacing. We train a support vector machine classifier on ratio metric values determined from healthy and simulated osteoporotic bone data, which we use to accurately classify osteoporotic bone.

We propose a semi-automatic algorithm for the segmentation of vertebral bodies in magnetic resonance (MR) images of the human lumbar spine. Quantitative analysis of spine MR images often necessitate segmentation of the image into specific regions representing anatomic structures of interest. Existing algorithms for vertebral body segmentation require heavy inputs from the user, which is a disadvantage. For example, the user needs to define individual regions of interest (ROIs) for each vertebral body, and specify parameters for the segmentation algorithm. To overcome these drawbacks, we developed a semi-automatic algorithm that considerably reduces the need for user inputs. First, we simplified the ROI placement procedure by reducing the requirement to only one ROI, which includes a vertebral body; subsequently, a correlation algorithm is used to identify the remaining vertebral bodies and to automatically detect the ROIs. Second, the detected ROIs are adjusted to facilitate the subsequent segmentation process. Third, the segmentation is performed via graph-based and line-based segmentation algorithms. We tested our algorithm on sagittal MR images of the lumbar spine and achieved a 90% dice similarity coefficient, when compared with manual segmentation. Our new semi-automatic method significantly reduces the user’s role while achieving good segmentation accuracy.

We propose a new deep learning network capable of successfully segmenting intervertebral discs and their complex boundaries from magnetic resonance (MR) spine images. The existing U-network (U-net) is known to perform well in various segmentation tasks in medical images; however, its performance with respect to details of segmentation such as boundaries is limited by the structural limitations of a max-pooling layer that plays a key role in feature extraction process in the U-net. We designed a modified convolutional and pooling layer scheme and applied a cascaded learning method to overcome these structural limitations of the max-pooling layer of a conventional U-net. The proposed network achieved 3% higher Dice similarity coefficient (DSC) than conventional U-net for intervertebral disc segmentation (89.44% vs. 86.44%, respectively; p < 0.001). For intervertebral disc boundary segmentation, the proposed network achieved 10.46% higher DSC than conventional U-net (54.62% vs. 44.16%, respectively; p < 0.001).

Tissue-engineered nasal septal cartilage may provide a source of autologous tissue for repair of craniofacial defects. Although advances have been made in manipulating the chondrocyte culture environment for production of neocartilage, consensus on the best oxygen tension for in vitro growth of tissue-engineered cartilage has not been reached. The objective of this study was to determine whether in vitro oxygen tension influences chondrocyte expansion and redifferentiation. Proliferation of chondrocytes from 12 patients expanded in monolayer under hypoxic (5% or 10%) or normoxic (21%) oxygen tension was compared over 14 days of culture. The highest performing oxygen level was used for further expansion of the monolayer cultures. At confluency, chondrocytes were redifferentiated by encapsulation in alginate beads and cultured for 14 days under hypoxic (5 or 10%) or normoxic (21%) oxygen tension. Biochemical and histological properties were evaluated. Chondrocyte proliferation in monolayer and redifferentiation in alginate beads were supported by all oxygen tensions tested. Chondrocytes in monolayer culture had increased proliferation at normoxic oxygen tension (p = 0.06), as well as greater accumulation of glycosaminoglycan (GAG) during chondrocyte redifferentiation (p < 0.05). Chondrocytes released from beads cultured under all three oxygen levels showed robust accumulation of GAG and type II collagen with a lower degree of type I collagen immunoreactivity. Finally, formation of chondrocyte clusters was associated with decreasing oxygen tension (p < 0.05). Expansion of human septal chondrocytes in monolayer culture was greatest at normoxic oxygen tension. Both normoxic and hypoxic culture of human septal chondrocytes embedded in alginate beads supported robust extracellular matrix deposition. However, GAG accumulation was significantly enhanced under normoxic culture conditions. Chondrocyte cluster formation was associated with hypoxic oxygen tension.

Inflammatory response and cell death in hepatocytes are hallmarks of chronic liver disease, and, therefore, can be effective therapeutic targets. Neurotropin® (NTP) is a drug widely used in Japan and China to treat chronic pain. Although NTP has been demonstrated to suppress chronic pain through the descending pain inhibitory system, the action mechanism of NTP remains elusive. We hypothesize that NTP functions to suppress inflammatory pathways, thereby attenuating disease progression. In the present study, we investigated whether NTP suppresses inflammatory signaling and cell death pathways induced by interleukin-1β (IL-1β) and tumor necrosis factor-α (TNFα) in hepatocytes. NTP suppressed nuclear factor-κB (NF-κB) activation induced by IL-1β and TNFα assessed by using hepatocytes isolated from NF-κB-green fluorescent protein (GFP) reporter mice and an NF-κB-luciferase reporter system. The expression of NF-κB target genes, Il6, Nos2, Cxcl1, ccl5 and Cxcl2 induced by IL-1β and TNFα was suppressed after NTP treatment. We also found that NTP suppressed the JNK phosphorylation induced by IL-1β and TNFα. Because JNK activation contributes to hepatocyte death, we determined that NTP treatment suppressed hepatocyte death induced by IL-1β and TNFα in combination with actinomycin D. Taken together, our data demonstrate that NTP attenuates IL-1β and TNFα-mediated inflammatory cytokine expression and cell death in hepatocytes through the suppression of NF-κB and JNK. The results from the present study suggest that NTP may become a preventive or therapeutic strategy for alcoholic and non-alcoholic fatty liver disease in which NF-κB and JNK are thought to take part.