transforming-growth-factor-beta and Low-Back-Pain

This systematic review aimed to investigate immune-inflammatory and hypothalamic-pituitary-adrenal (HPA) axis biomarkers in individuals with non-specific low back pain (NSLBP) compared to healthy control. The search was performed in five databases until 4 November 2021. Two reviewers independently conducted screenings, data extraction, risk of bias, and methodological quality assessment of 14 unique studies. All studies reported the source of the fluid analyzed: nine studies used serum, two used plasma, one used serum and plasma, and two studies used salivary cortisol. We found preliminary and limited evidence (only one study for each biomarker) of increased levels in growth differentiation factor 15 (GDF-15), interleukin-23 (IL-23), transforming growth factor-beta (TGF-β), and soluble tumor necrosis factor receptor 1 (sTNF-R1) in NSLBP. Inconsistent and limited evidence was identified for interleukin-10 (IL-10). Although C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) levels appear to increase in NSLBP, only one study per each biomarker reported statistically significant differences. Interleukin-1 beta (IL-1β), interleukin-17 (IL-17), interferon gamma (IFN-γ), and high-sensitivity CRP (hsCRP) showed no significant differences. Regarding cortisol, one study showed a significant increase and another a significant decrease. More robust evidence between GDF-15, IL-23, TGF-β, and sTNF-R1 with NSLBP is needed. Moreover, contrary to the findings reported in previous studies, when comparing results exclusively with healthy control, insufficient robust evidence for IL-6, TNF-α, and CRP was found in NSLBP. In addition, cortisol response (HPA-related biomarker) showed a dysregulated functioning in NSLBP, with incongruent evidence regarding its directionality. Therefore, our effort is to find adjusted evidence to conclude which immune-inflammatory and HPA axis biomarkers are altered in NSLBP and how much their levels are affected.. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020176153, identifier CRD42020176153.

Topics: Biomarkers; C-Reactive Protein; Growth Differentiation Factor 15; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Interferon-gamma; Interleukin-10; Interleukin-17; Interleukin-1beta; Interleukin-23; Interleukin-6; Low Back Pain; Pituitary-Adrenal System; Receptors, Tumor Necrosis Factor; Transforming Growth Factor beta; Transforming Growth Factors; Tumor Necrosis Factor-alpha

The most effective way to control severity and mortality rate of the novel coronavirus disease (COVID-19) is through sensitive diagnostic approaches and an appropriate treatment protocol. We aimed to identify the effect of adding corticosteroid and Tocilizumab to a standard treatment protocol in treating COVID-19 patients with chronic disease through hematological and lab biomarkers.. This study was performed retrospectively on 68 COVID-19 patients with chronic disease who were treated by different therapeutic protocols. The patients were categorized into four groups: control group represented the patients' lab results at admission before treatment protocols were applied; group 1 included patients treated with anticoagulants, Hydroxychloroquine, and antibiotics; group 2 comprised patients treated with Dexamethasone; and group 3 included patients treated with Dexamethasone and Tocilizumab.. The study paves the way into the effectiveness of combining Dexamethasone with Tocilizumab in treatment COVID-19 patients with chronic diseases.. La forma más eficaz de controlar la gravedad y la tasa de mortalidad de la enfermedad del nuevo coronavirus (COVID-19) es mediante enfoques de diagnóstico sensibles y un protocolo de tratamiento adecuado. Nuestro objetivo fue identificar el efecto de agregar corticosteroides y tocilizumab a un protocolo de tratamiento estándar en el tratamiento de pacientes con COVID-19 con enfermedad crónica a través de biomarcadores hematológicos y de laboratorio.. Este estudio se realizó de forma retrospectiva en 68 pacientes COVID-19 con enfermedad crónica que fueron tratados por diferentes protocolos terapéuticos. Los pacientes se clasificaron en cuatro grupos: el grupo de control representaba los resultados de laboratorio de los pacientes en el momento de la admisión antes de que se aplicaran los protocolos de tratamiento; el grupo 1 incluyó a pacientes tratados con anticoagulantes, hidroxicloroquina y antibióticos; el grupo 2 estaba compuesto por pacientes tratados con dexametasona; y el grupo 3 incluyó a pacientes tratados con dexametasona y tocilizumab.. El estudio allana el camino hacia la eficacia de la combinación de dexametasona con tocilizumab en el tratamiento de pacientes con COVID-19 con enfermedades crónicas.. The Child-Mother Index constitutes a potential useful risk factor indicator for statistical analyses on data after birth. The value of the Child-Mother Index based on the estimated fetal weight before birth deserves evaluation.. Six ceria supports synthesized by various synthesis methodologies were used to deposit cobalt oxide. The catalysts were thoroughly characterized, and their catalytic activity for complete methane oxidation was studied. The supports synthesized by direct calcination and precipitation with ammonia exhibited the best textural and structural properties as well as the highest degree of oxidation. The remaining supports presented poorer textural properties to be employed as catalytic supports. The cobalt deposited over the first two supports presented a good dispersion at the external surface, which induced a significant redox effect that increased the number of Co. Some studies show that children with obesity are more likely to receive a diagnosis of depression, anxiety, or attention-deficit hyperactivity disorder (ADHD). But this does not necessarily mean obesity causes these conditions. Depression, anxiety, or ADHD could cause obesity. A child's environment, including family income or their parents' mental health, could also affect a child's weight and mental health. Understanding the nature of these relationships could help scientists develop better interventions for both obesity and mental health conditions. Genetic studies may help scientists better understand the role of the environment in these conditions, but it's important to consider both the child's and their parents’ genetics in these analyses. This is because parents and children share not only genes, but also environmental conditions. For example, families that carry genetic variants associated with higher body weight might also have lower incomes, if parents have been affected by biases against heavier people in society and the workplace. Children in these families could have worse mental health because of effects of their parent’s weight, rather than their own weight. Looking at both child and adult genetics can help disentangle these processes. Hughes et al. show that a child's own body mass index, a ratio of weight and height, is not strongly associated with the child’s mental health symptoms. They analysed genetic, weight, and health survey data from about 41,000 8-year-old children and their parents. The results suggest that a child's own BMI does not have a large effect on their anxiety symptoms. There was also no clear evidence that a child's BMI affected their symptoms of depression or ADHD. These results contradict previous studies, which did not account for parental genetics. Hughes et al. suggest that, at least for eight-year-olds, factors linked with adult weight and which differ between families may be more critical to a child's mental health than a child’s own weight. For older children and adolescents, this may not be the case, and the individual’s own weight may be more important. As a result, policies designed to reduce obesity in mid-childhood are unlikely to greatly improve the mental health of children. On the other hand, policies targeting the environmental or societal factors contributing to higher body weights, bias against people with higher weights, and poor child mental health directly may be more beneficial.. The development of an efficient photocatalyst for C2 product formation from CO. Оценка антиастенического эффекта последовательной терапии левокарнитином (ЛК) и ацетилкарнитином (АЛК) пациентов с артериальной гипертензией и/или ишемической болезнью сердца (ИБС) с астеническим синдромом (АС).. В открытое сравнительное исследование были включены 120 пациентов в возрасте 54—67 лет с артериальной гипертензией и/или ИБС с АС. Пациенты 1-й группы (. У больных 1-й группы отмечено статистически значимое уменьшение различных проявлений АС. Отличия носили достоверный характер по сравнению как с исходным уровнем, так и со 2-й группой. Установлено эндотелийпротективное действие ЛК и АЛК.. Полученные результаты свидетельствуют, что у таких коморбидных пациентов использование ЛК и АЛК уменьшает выраженность проявлений АС, а установленные эндотелиотропные свойства препаратов позволяют рекомендовать их в составе комплексной персонифицированной терапии пациентов с сердечно-сосудистыми заболеваниями.. Naproxen sodium 440 mg/diphenhydramine 50 mg combination demonstrated improvement in sleep maintenance (WASO) vs. naproxen sodium 550 mg and higher efficiency in average daily pain reduction compared with the comparison groups. The treatment was well tolerated There were no serious or unexpected adverse events reported in the study.. Сравнительный анализ эффективности и безопасности новой комбинации напроксена натрия и дифенгидрамина у пациентов с неспецифическим болевым синдромом в пояснично-крестцовом отделе спины (M54.5 «Боль внизу спины») и нарушением сна (G47.0 «Нарушения засыпания и поддержания сна [бессонница]»).. Проведено проспективное многоцентровое рандомизированное открытое сравнительное в параллельных группах клиническое исследование. Пациенты были рандомизированы в 3 группы. Больные 1-й группы получали напроксен натрия (440 мг) и дифенгидрамин (50 мг), 2-й — напроксен натрия (550 мг), 3-й — парацетамол (1000 мг) и дифенгидрамин (50 мг). Исследуемые препараты пациенты принимали однократно перед сном в течение 3 дней. Все пациенты также принимали 275 мг (1 таблетка) напроксена натрия в качестве препарата фоновой терапии. Первичным критерием эффективности было общее время бодрствования после наступления сна (WASO), измеряемое методом актиграфии. Также использовались критерии оценки продолжительности и качества сна и выраженности боли.. Анализ эффективности проведен для ITT популяции (. Применение комбинации напроксена натрия (440 мг) и дифенгидрамина (50 мг) характеризовалось более выраженным поддержанием сна по сравнению с напроксеном натрия 550 мг и более высокой эффективностью в отношении снижения интенсивности боли по сравнению со 2-й и 3-й группами. Отмечена хорошая переносимость препарата, серьезных нежелательных явлений зарегистрировано не было.

Topics: Acetaminophen; Acetylcarnitine; Acetylcholinesterase; Acids; Acinetobacter baumannii; Acinetobacter Infections; Adaptation, Psychological; Adolescent; Adsorption; Adult; Aged; Alcohol Drinking; Alzheimer Disease; Amikacin; Ammonia; Anaerobiosis; Animals; Anorexia; Anti-Bacterial Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Anxiety; Aptamers, Nucleotide; Asthenia; Attention Deficit Disorder with Hyperactivity; Bacterial Proteins; Beryllium; beta-Lactamases; Biofuels; Biomass; Biosensing Techniques; Bismuth; Blister; Body Mass Index; Body Surface Area; Boronic Acids; Brain; Breast Neoplasms; Butyrylcholinesterase; Cannabis; Carbapenems; Carbonyl Cyanide m-Chlorophenyl Hydrazone; Carboxylic Acids; Carcinoma, Hepatocellular; Cardiovascular Diseases; Carnitine; Case-Control Studies; Catalysis; Cell Cycle Proteins; Cell Line, Tumor; Cell Proliferation; Child; China; Cholinesterase Inhibitors; Clarithromycin; Clostridioides; Clostridioides difficile; Clostridium Infections; Cohort Studies; Colistin; Colitis; Colon; Coloring Agents; Coronary Artery Bypass; Creatinine; Crystalloid Solutions; Cytokines; Depression; Dextran Sulfate; Dextrans; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Diarrhea; Dietary Supplements; Diphenhydramine; Disease Models, Animal; Disease Outbreaks; Double-Blind Method; Doxorubicin; Drosophila; Drug Tapering; Dysbiosis; Electrons; Escherichia coli; Extracellular Vesicles; Fatigue; Female; Fermentation; gamma-Cyclodextrins; Gastrointestinal Microbiome; Glucose; Graft Survival; Graft vs Host Disease; Head and Neck Neoplasms; Heart Arrest, Induced; Hematopoietic Stem Cell Transplantation; High-Intensity Interval Training; Hippocampus; Humans; Hydrogen-Ion Concentration; Hypertension; Incidence; Interferon-gamma; Italy; Kinetics; Klebsiella Infections; Klebsiella pneumoniae; Lab-On-A-Chip Devices; Lactoferrin; Larva; Length of Stay; Lignin; Liver; Liver Neoplasms; Liver Transplantation; Living Donors; Low Back Pain; Lung; Lung Volume Measurements; Macrophages; Male; Melphalan; Men; Mendelian Randomization Analysis; Meropenem; Methane; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; Mitochondrial Proteins; Molecular Docking Simulation; Molecular Structure; Mothers; Motivation; Mycoplasma; Mycoplasma hominis; Mycoplasma Infections; NAD; Nanocomposites; Nanoparticles; Nanotubes, Carbon; Naproxen; Neovascularization, Pathologic; Neurons; Nitrates; Nucleolin; Opuntia; Paratyphoid Fever; Phenotype; Phosphatidylinositol 3-Kinases; Phytochemicals; Plant Extracts; Pregnancy; Prevalence; Prospective Studies; Proto-Oncogene Proteins c-akt; Pulmonary Disease, Chronic Obstructive; Rats; Rats, Wistar; Resveratrol; Retrospective Studies; Rifampin; Risk Factors; RNA, Messenger; Selenium; Sleep; Social Behavior; Soil; Soil Pollutants; Squamous Cell Carcinoma of Head and Neck; Staphylococcus aureus; Structure-Activity Relationship; Suicidal Ideation; Suicide; Superoxide Dismutase-1; Surveys and Questionnaires; Swimming; Syndrome; Tannins; Temperature; Transforming Growth Factor beta; Transplantation Conditioning; Treatment Outcome; Triple Negative Breast Neoplasms; Troponin T; Tumor Microenvironment; United Kingdom; Ureaplasma; Ureaplasma urealyticum; Urinary Tract Infections; Viscum; Waste Disposal Facilities; Wastewater; Water; Water Pollutants, Chemical; Wolfiporia; Young Adult

Pain coming from the sacroiliac (SI) joints can explain up to 25% of all chronic low back pain. A careful differential diagnosis is required to avoid misdiagnosis of low back pain. In addition to historical findings, positive findings on physical examination maneuvers that stress the SI joint are a key component diagnosis. The SI joint is confirmed as a pain generator when intraarticular injection of local anaesthetics provides acute back pain relief. Minimally invasive SI joint fusion is clearly superior to invasive open surgical procedures, with decreased blood loss and tissue disruption, shorter procedure times and shorter hospital stays. Especially well documented are the results of minimally invasive SI joint fusion using iFuse Implant System. Pathologische Veränderungen an den Iliosakralgelenken (ISG) müssen in bis zu 25% als Ursache einer schweren Schmerzsymptomatik im unteren Rückenbereich angesehen werden. Es wird eine sorgfältige differenzialdiagnostische Abklärung benötigt, um eine Fehlinterpretation der von den Patienten geäußerten Beschwerden zu vermeiden bzw. eine Arthropathie im Iliosakralgelenk zu identifizieren. Neben einer umfassenden Aufnahme der Anamnese bilden positive Resultate unterschiedlicher Provokationstests wichtige Anhaltspunkte für die richtige Diagnosestellung. Als vorrangiger Beleg für die definitive Diagnose und damit auch für eine Operationsempfehlung wird jedoch die Schmerzlinderung nach wiederholter intraartikulärer Injektion eines Lokalanästhetikums angesehen. Mithilfe konservativer Behandlungsmaßnahmen (Analgetika/Neuroleptika) und physikalischer Maßnahmen kann symptomatisch eine meist mäßige Besserung erreicht werden. Bei den operativen Maßnahmen zeigt sich eine deutliche Überlegenheit der minimalinvasiven Eingriffe gegenüber offenen, invasiveren operativen Verfahren. Besonders gut dokumentiert sind die Resultate der minimalinvasiven Operationen mit dem iFuse Implant System

Topics: Arthrodesis; Biocompatible Materials; Bone Morphogenetic Protein 2; Diagnosis, Differential; Equipment Design; Humans; Low Back Pain; Minimally Invasive Surgical Procedures; Outcome and Process Assessment, Health Care; Pain Measurement; Physical Examination; Prostheses and Implants; Recombinant Proteins; Sacroiliac Joint; Sacroiliitis; Transforming Growth Factor beta

Because of significant complications related to the use of autologous bone grafts in spinal fusion surgery, bone substitutes and growth factors such as bone morphogenetic protein (BMP) have been developed. One of them, recombinant human (rh) BMP-2, has been approved by the Food and Drug Administration (FDA) for use under precise conditions. However, rhBMP-2-related side effects have been reported, used in FDA-approved procedures, but also in off-label use.A systematic review of clinical data was conducted to analyse the rhBMP-2-related adverse events (AEs), in order to assess their prevalence and the associated surgery practices.. Medline search with keywords "bone morphogenetic protein 2", "lumbar spine", "anterolateral interbody fusion" (ALIF) and the filter "clinical trial". FDA published reports were also included. Study assessment was made by authors (experienced spine surgeons), based on quality of study designs and level of evidence.. Extensive review of randomised controlled trials (RCTs) and controlled series published up to the present point, reveal no evidence of a significant increase of AEs related to rhBMP-2 use during ALIF surgeries, provided that it is used following FDA guidelines. Two additional RCTs performed with rhBMP-2 in combination with allogenic bone dowels reported increased bone remodelling in BMP-treated patients. This AE was transient and had no consequence on the clinical outcome of the patients. No other BMP-related AEs were reported in these studies.. This literature review confirms that the use of rhBMP-2 following FDA-approved recommendations (i.e. one-level ALIF surgery with an LT-cage) is safe. The rate of complications is low and the AEs had been identified by the FDA during the pre-marketing clinical trials. The clinical efficiency of rhBMP-2 is equal or superior to that of allogenic or autologous bone graft in respect to fusion rate, low back pain disability, patient satisfaction and rate of re-operations. For all other off-label use, the safety and effectiveness of rhBMP-2 have not been established, and further RCTs with high level of evidence are required.

Topics: Adult; Bone Morphogenetic Protein 2; Bone Transplantation; Female; Humans; Low Back Pain; Lumbar Vertebrae; Male; Middle Aged; Off-Label Use; Postoperative Complications; Recombinant Proteins; Spinal Fusion; Transforming Growth Factor beta

Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is a single-gene disorder directly affecting the cerebral small blood vessels, that is caused by mutations in the HTRA1 gene encoding HtrA serine peptidase/protease 1 (HTRA1). CARASIL is the second known genetic form of ischemic, nonhypertensive, cerebral small-vessel diseases with an identified gene, following CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy). The exact prevalence of CARASIL is currently unknown, and so far about 50 patients have been reported, most of them from Japan and two from China. Genetically no founder haplotype has been identified, and so the disease is expected to be found more widely. The main clinical manifestations are ischemic stroke or stepwise deterioration in brain functions, progressive dementia, premature baldness, and attacks of severe low back pain or spondylosis deformans/disk herniation. The most characteristic brain MRI findings are homogeneously confluent white-matter changes and multiple lacunar infarctions in the basal ganglia and thalamus. Histopathologically, CARASIL is characterized by intense arteriosclerosis, mainly in the small penetrating arteries, without granular osmiophilic materials (GOM) or amyloid deposition. CARASIL is a prototype single-gene disorder of cerebral small vessels, secondary to and distinct from CADASIL. CARASIL-associated mutant HTRA1s exhibited decreased protease activity and failed to repress transforming growth factor-β (TGF-β) family signaling, indicating that the increased TGF-β signaling causes arteriopathy in CARASIL. Therefore, HTRA1 represents another new gene to be considered in future studies of the mechanisms and therapeutic strategies of cerebral small-vessel diseases, as well as alopecia and degenerative vertebral/disk diseases.

Topics: Adult; Alopecia; Blood Vessels; Brain; Cerebral Infarction; Dementia, Vascular; Genes, Recessive; High-Temperature Requirement A Serine Peptidase 1; Humans; Leukoencephalopathy, Progressive Multifocal; Low Back Pain; Male; Middle Aged; Mutation; Serine Endopeptidases; Spondylosis; Syndrome; Transforming Growth Factor beta

Topics: Adolescent; Adult; Animals; Biolistics; Bone Morphogenetic Protein 7; Bone Morphogenetic Proteins; Growth Substances; Humans; Intervertebral Disc; Intervertebral Disc Displacement; Low Back Pain; Middle Aged; Regeneration; Tissue Engineering; Transforming Growth Factor beta

The most effective way to control severity and mortality rate of the novel coronavirus disease (COVID-19) is through sensitive diagnostic approaches and an appropriate treatment protocol. We aimed to identify the effect of adding corticosteroid and Tocilizumab to a standard treatment protocol in treating COVID-19 patients with chronic disease through hematological and lab biomarkers.. This study was performed retrospectively on 68 COVID-19 patients with chronic disease who were treated by different therapeutic protocols. The patients were categorized into four groups: control group represented the patients' lab results at admission before treatment protocols were applied; group 1 included patients treated with anticoagulants, Hydroxychloroquine, and antibiotics; group 2 comprised patients treated with Dexamethasone; and group 3 included patients treated with Dexamethasone and Tocilizumab.. The study paves the way into the effectiveness of combining Dexamethasone with Tocilizumab in treatment COVID-19 patients with chronic diseases.. La forma más eficaz de controlar la gravedad y la tasa de mortalidad de la enfermedad del nuevo coronavirus (COVID-19) es mediante enfoques de diagnóstico sensibles y un protocolo de tratamiento adecuado. Nuestro objetivo fue identificar el efecto de agregar corticosteroides y tocilizumab a un protocolo de tratamiento estándar en el tratamiento de pacientes con COVID-19 con enfermedad crónica a través de biomarcadores hematológicos y de laboratorio.. Este estudio se realizó de forma retrospectiva en 68 pacientes COVID-19 con enfermedad crónica que fueron tratados por diferentes protocolos terapéuticos. Los pacientes se clasificaron en cuatro grupos: el grupo de control representaba los resultados de laboratorio de los pacientes en el momento de la admisión antes de que se aplicaran los protocolos de tratamiento; el grupo 1 incluyó a pacientes tratados con anticoagulantes, hidroxicloroquina y antibióticos; el grupo 2 estaba compuesto por pacientes tratados con dexametasona; y el grupo 3 incluyó a pacientes tratados con dexametasona y tocilizumab.. El estudio allana el camino hacia la eficacia de la combinación de dexametasona con tocilizumab en el tratamiento de pacientes con COVID-19 con enfermedades crónicas.. The Child-Mother Index constitutes a potential useful risk factor indicator for statistical analyses on data after birth. The value of the Child-Mother Index based on the estimated fetal weight before birth deserves evaluation.. Six ceria supports synthesized by various synthesis methodologies were used to deposit cobalt oxide. The catalysts were thoroughly characterized, and their catalytic activity for complete methane oxidation was studied. The supports synthesized by direct calcination and precipitation with ammonia exhibited the best textural and structural properties as well as the highest degree of oxidation. The remaining supports presented poorer textural properties to be employed as catalytic supports. The cobalt deposited over the first two supports presented a good dispersion at the external surface, which induced a significant redox effect that increased the number of Co. Some studies show that children with obesity are more likely to receive a diagnosis of depression, anxiety, or attention-deficit hyperactivity disorder (ADHD). But this does not necessarily mean obesity causes these conditions. Depression, anxiety, or ADHD could cause obesity. A child's environment, including family income or their parents' mental health, could also affect a child's weight and mental health. Understanding the nature of these relationships could help scientists develop better interventions for both obesity and mental health conditions. Genetic studies may help scientists better understand the role of the environment in these conditions, but it's important to consider both the child's and their parents’ genetics in these analyses. This is because parents and children share not only genes, but also environmental conditions. For example, families that carry genetic variants associated with higher body weight might also have lower incomes, if parents have been affected by biases against heavier people in society and the workplace. Children in these families could have worse mental health because of effects of their parent’s weight, rather than their own weight. Looking at both child and adult genetics can help disentangle these processes. Hughes et al. show that a child's own body mass index, a ratio of weight and height, is not strongly associated with the child’s mental health symptoms. They analysed genetic, weight, and health survey data from about 41,000 8-year-old children and their parents. The results suggest that a child's own BMI does not have a large effect on their anxiety symptoms. There was also no clear evidence that a child's BMI affected their symptoms of depression or ADHD. These results contradict previous studies, which did not account for parental genetics. Hughes et al. suggest that, at least for eight-year-olds, factors linked with adult weight and which differ between families may be more critical to a child's mental health than a child’s own weight. For older children and adolescents, this may not be the case, and the individual’s own weight may be more important. As a result, policies designed to reduce obesity in mid-childhood are unlikely to greatly improve the mental health of children. On the other hand, policies targeting the environmental or societal factors contributing to higher body weights, bias against people with higher weights, and poor child mental health directly may be more beneficial.. The development of an efficient photocatalyst for C2 product formation from CO. Оценка антиастенического эффекта последовательной терапии левокарнитином (ЛК) и ацетилкарнитином (АЛК) пациентов с артериальной гипертензией и/или ишемической болезнью сердца (ИБС) с астеническим синдромом (АС).. В открытое сравнительное исследование были включены 120 пациентов в возрасте 54—67 лет с артериальной гипертензией и/или ИБС с АС. Пациенты 1-й группы (. У больных 1-й группы отмечено статистически значимое уменьшение различных проявлений АС. Отличия носили достоверный характер по сравнению как с исходным уровнем, так и со 2-й группой. Установлено эндотелийпротективное действие ЛК и АЛК.. Полученные результаты свидетельствуют, что у таких коморбидных пациентов использование ЛК и АЛК уменьшает выраженность проявлений АС, а установленные эндотелиотропные свойства препаратов позволяют рекомендовать их в составе комплексной персонифицированной терапии пациентов с сердечно-сосудистыми заболеваниями.. Naproxen sodium 440 mg/diphenhydramine 50 mg combination demonstrated improvement in sleep maintenance (WASO) vs. naproxen sodium 550 mg and higher efficiency in average daily pain reduction compared with the comparison groups. The treatment was well tolerated There were no serious or unexpected adverse events reported in the study.. Сравнительный анализ эффективности и безопасности новой комбинации напроксена натрия и дифенгидрамина у пациентов с неспецифическим болевым синдромом в пояснично-крестцовом отделе спины (M54.5 «Боль внизу спины») и нарушением сна (G47.0 «Нарушения засыпания и поддержания сна [бессонница]»).. Проведено проспективное многоцентровое рандомизированное открытое сравнительное в параллельных группах клиническое исследование. Пациенты были рандомизированы в 3 группы. Больные 1-й группы получали напроксен натрия (440 мг) и дифенгидрамин (50 мг), 2-й — напроксен натрия (550 мг), 3-й — парацетамол (1000 мг) и дифенгидрамин (50 мг). Исследуемые препараты пациенты принимали однократно перед сном в течение 3 дней. Все пациенты также принимали 275 мг (1 таблетка) напроксена натрия в качестве препарата фоновой терапии. Первичным критерием эффективности было общее время бодрствования после наступления сна (WASO), измеряемое методом актиграфии. Также использовались критерии оценки продолжительности и качества сна и выраженности боли.. Анализ эффективности проведен для ITT популяции (. Применение комбинации напроксена натрия (440 мг) и дифенгидрамина (50 мг) характеризовалось более выраженным поддержанием сна по сравнению с напроксеном натрия 550 мг и более высокой эффективностью в отношении снижения интенсивности боли по сравнению со 2-й и 3-й группами. Отмечена хорошая переносимость препарата, серьезных нежелательных явлений зарегистрировано не было.

Topics: Acetaminophen; Acetylcarnitine; Acetylcholinesterase; Acids; Acinetobacter baumannii; Acinetobacter Infections; Adaptation, Psychological; Adolescent; Adsorption; Adult; Aged; Alcohol Drinking; Alzheimer Disease; Amikacin; Ammonia; Anaerobiosis; Animals; Anorexia; Anti-Bacterial Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Anxiety; Aptamers, Nucleotide; Asthenia; Attention Deficit Disorder with Hyperactivity; Bacterial Proteins; Beryllium; beta-Lactamases; Biofuels; Biomass; Biosensing Techniques; Bismuth; Blister; Body Mass Index; Body Surface Area; Boronic Acids; Brain; Breast Neoplasms; Butyrylcholinesterase; Cannabis; Carbapenems; Carbonyl Cyanide m-Chlorophenyl Hydrazone; Carboxylic Acids; Carcinoma, Hepatocellular; Cardiovascular Diseases; Carnitine; Case-Control Studies; Catalysis; Cell Cycle Proteins; Cell Line, Tumor; Cell Proliferation; Child; China; Cholinesterase Inhibitors; Clarithromycin; Clostridioides; Clostridioides difficile; Clostridium Infections; Cohort Studies; Colistin; Colitis; Colon; Coloring Agents; Coronary Artery Bypass; Creatinine; Crystalloid Solutions; Cytokines; Depression; Dextran Sulfate; Dextrans; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Diarrhea; Dietary Supplements; Diphenhydramine; Disease Models, Animal; Disease Outbreaks; Double-Blind Method; Doxorubicin; Drosophila; Drug Tapering; Dysbiosis; Electrons; Escherichia coli; Extracellular Vesicles; Fatigue; Female; Fermentation; gamma-Cyclodextrins; Gastrointestinal Microbiome; Glucose; Graft Survival; Graft vs Host Disease; Head and Neck Neoplasms; Heart Arrest, Induced; Hematopoietic Stem Cell Transplantation; High-Intensity Interval Training; Hippocampus; Humans; Hydrogen-Ion Concentration; Hypertension; Incidence; Interferon-gamma; Italy; Kinetics; Klebsiella Infections; Klebsiella pneumoniae; Lab-On-A-Chip Devices; Lactoferrin; Larva; Length of Stay; Lignin; Liver; Liver Neoplasms; Liver Transplantation; Living Donors; Low Back Pain; Lung; Lung Volume Measurements; Macrophages; Male; Melphalan; Men; Mendelian Randomization Analysis; Meropenem; Methane; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; Mitochondrial Proteins; Molecular Docking Simulation; Molecular Structure; Mothers; Motivation; Mycoplasma; Mycoplasma hominis; Mycoplasma Infections; NAD; Nanocomposites; Nanoparticles; Nanotubes, Carbon; Naproxen; Neovascularization, Pathologic; Neurons; Nitrates; Nucleolin; Opuntia; Paratyphoid Fever; Phenotype; Phosphatidylinositol 3-Kinases; Phytochemicals; Plant Extracts; Pregnancy; Prevalence; Prospective Studies; Proto-Oncogene Proteins c-akt; Pulmonary Disease, Chronic Obstructive; Rats; Rats, Wistar; Resveratrol; Retrospective Studies; Rifampin; Risk Factors; RNA, Messenger; Selenium; Sleep; Social Behavior; Soil; Soil Pollutants; Squamous Cell Carcinoma of Head and Neck; Staphylococcus aureus; Structure-Activity Relationship; Suicidal Ideation; Suicide; Superoxide Dismutase-1; Surveys and Questionnaires; Swimming; Syndrome; Tannins; Temperature; Transforming Growth Factor beta; Transplantation Conditioning; Treatment Outcome; Triple Negative Breast Neoplasms; Troponin T; Tumor Microenvironment; United Kingdom; Ureaplasma; Ureaplasma urealyticum; Urinary Tract Infections; Viscum; Waste Disposal Facilities; Wastewater; Water; Water Pollutants, Chemical; Wolfiporia; Young Adult

The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in anterior lumbar interbody fusion (ALIF) is controversial regarding the reported complication rates and cost. The authors aimed to assess the complication rates of performing ALIF using rhBMP-2.. This is a prospective study of consecutive patients who underwent ALIF performed by a single spine surgeon and a single vascular surgeon between 2009 and 2012. All patients underwent placement of a polyetheretherketone (PEEK) cage filled with rhBMP-2 and a separate anterior titanium plate. Preoperative clinical data, operative details, postoperative complications, and clinical and radiographic outcomes were recorded for all patients. Clinical outcome measures included back and leg pain visual analog scale scores, Oswestry Disability Index (ODI), and SF-36 Physical and Mental Component Summary (PCS and MCS) scores. Radiographic assessment of fusion was performed using high-definition CT scanning. Male patients were screened pre- and postoperatively regarding sexual dysfunction, specifically retrograde ejaculation (RE).. The study comprised 131 patients with a mean age of 45.3 years. There were 67 men (51.1%) and 64 women (48.9%). Of the 131 patients, 117 (89.3%) underwent ALIF at L5-S1, 9 (6.9%) at L4-5, and 5 (3.8%) at both L4-5 and L5-S1. The overall complication rate was 19.1% (25 of 131), with 17 patients (13.0%) experiencing minor complications and 8 (6.1%) experiencing major complications. The mean estimated blood loss per ALIF level was 115 ml. There was 1 incidence (1.5%) of RE. No significant vascular injuries occurred. No prosthesis failure occurred with the PEEK cage and separate anterior screw-plate. Back and leg pain improved 57.2% and 61.8%, respectively. The ODI improved 54.3%, with PCS and MCS scores improving 41.7% and 21.3%, respectively. Solid interbody fusion was observed in 96.9% of patients at 12 months.. Anterior lumbar interbody fusion with a vascular access surgeon and spine surgeon, using a separate cage and anterior screw-plate, provides a very robust and reliable construct with low complication rates, high fusion rates, and positive clinical outcomes, and it is cost-effective. The authors did not experience the high rates of RE reported by other authors using rhBMP-2.

Topics: Adult; Aged; Benzophenones; Bone Morphogenetic Protein 2; Bone Plates; Bone Screws; Ejaculation; Erectile Dysfunction; Female; Humans; Intervertebral Disc Degeneration; Intervertebral Disc Displacement; Ketones; Low Back Pain; Lumbar Vertebrae; Male; Middle Aged; Polyethylene Glycols; Polymers; Prospective Studies; Recombinant Proteins; Sacrum; Spinal Fusion; Titanium; Transforming Growth Factor beta; Treatment Outcome; Young Adult

The authors compared fusion rates in transforaminal lumbar interbody fusion (TLIFs) when using either autograft or bone morphogenetic protein (BMP) placed in the interbody space.. Between September 2002 and December 2003, the authors performed 44 TLIF operations. Follow-up data were available for 40 patients. Of the 40 procedures, 19 involved cages filled with iliac crest autograft (Group 1) and 21 involved cages filled with a medium kit of recombinant human (rh) BMP-2 (Group 2). In all Group 2 patients, one BMP sponge was placed anterior to the cage and another was placed within the cage. In 12 of the Group 2 patients, iliac crest autograft was placed posterior to the BMP-filled cage (Group 2A). In the remaining nine Group 2 patients, only local autograft was placed posterior to the BMP-filled cage (Group 2B). Assessment of fusion was performed using dynamic radiography at 3-month intervals. Outcomes were assessed using the Prolo Scale, and iliac crest donor site pain was measured using a Visual Analog Scale (VAS). The mean follow-up period was 9 months (range 3-18 months). In Group 1 patients, one pseudarthrosis was detected. In Group 2 patients, dynamic radiography demonstrated solid fusion in all patients except one in Group 2B. Fifty-eight percent of patients in whom iliac crest autograft was used complained of donor site pain 6 months after surgery (5 of 10 points on the VAS). Symptomatic foraminal bone formation was not observed in any Group 2 patient.. The use of rhBMP-2 is safe in TLIFs when the sponges are placed away from the dura mater, and BMP promotes a more rapid fusion than iliac crest autograft alone. The use of rhBMP-2 in combination with local autograft is an excellent option for promoting solid fusion with TLIF, and it eliminates the possibility of iliac donor site pain.

Topics: Adult; Aged; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Transplantation; Combined Modality Therapy; Female; Follow-Up Studies; Humans; Ilium; Intervertebral Disc Displacement; Low Back Pain; Lumbar Vertebrae; Male; Middle Aged; Pilot Projects; Radiography; Recombinant Proteins; Spinal Fusion; Spondylolisthesis; Surgical Sponges; Transforming Growth Factor beta

In a multicenter, prospective, randomized, nonblinded, 2-year study, 279 patients with degenerative lumbar disc disease were randomly divided into two groups that underwent interbody fusion using two tapered threaded fusion cages. The investigational group (143 patients) received rhBMP-2 on an absorbable collagen sponge, and a control group (136 patients) received autogenous iliac crest bone graft. Plain radiographs and computed tomographic scans were used to evaluate fusion at 6, 12, and 24 months after surgery. Mean operative time (1.6 hours) and blood loss (109.8 mL) were less in the investigational rhBMP-2 group than in the autograft control group (2.0 hours and 153.1 mL). At 24 months the investigational group's fusion rate (94.5%) remained higher than that of the control group (88.7%). New bone formation occurred in all investigational patients. At all intervals, mean postoperative Oswestry, back pain, and leg pain scores and neurologic status improved in both treatment groups with similar outcomes. In the control group, eight adverse events related to the iliac crest graft harvest occurred (5.9%), and at 24 months 32% of patients reported graft site discomfort and 16% were bothered by its appearance. Lumbar fusion using rhBMP-2 and a tapered titanium fusion cage can yield a solid union and eliminate the need for harvesting iliac crest bone graft.

Topics: Adult; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Regeneration; Bone Transplantation; Female; Humans; Low Back Pain; Lumbar Vertebrae; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Spinal Diseases; Spinal Fusion; Time Factors; Tomography, X-Ray Computed; Transforming Growth Factor beta; Transplantation, Autologous; Treatment Outcome

A prospective, nonblinded, multicenter study of outcomes in patients undergoing single-level anterior lumbar discectomy and interbody fusion with InFUSE Bone Graft.. To determine the safety and effectiveness of InFUSE Bone Graft applied to an absorbable collagen sponge in anterior lumbar interbody fusion with threaded cortical allografts.. In primates, InFUSE Bone Graft used with allograft dowels was shown to increase rates of interbody fusion by promoting osteoinduction and enhancing incorporation of the allograft. Recently, in a small series of human patients undergoing anterior lumbar interbody fusion with a tapered cylindrical metal fusion cage, InFUSE Bone Graft has been shown to promote osteoinduction and fusion.. Forty-six patients underwent a single-level anterior lumbar discectomy and interbody fusion at five investigational sites. They were randomly assigned to one of two groups, and the results in the investigational patients who received threaded cortical allograft dowels with InFUSE Bone Graft were compared with those in the control patients who received threaded allograft dowels with autogenous iliac crest bone graft. Patients' clinical outcomes were assessed using neurologic status, work status, and Oswestry Low Back Pain Disability, Short Form-36, and back and leg pain questionnaires. Anteroposterior, lateral, flexion-extension radiographs, and computed tomography scans were used to evaluate the progression of fusion at 6, 12, and 24 months after surgery.. All patients who received InFUSE Bone Graft showed radiographic evidence of bony induction and early incorporation of the cortical allografts. All patients in this group had fusions at 12 months that remained fused at 24 months. At 12 and 24 months, the investigational group showed higher rates of fusion and improved neurologic status and back and leg pain when compared with the control group. There were no unanticipated adverse events related to the use of InFUSE Bone Graft.. The use of InFUSE Bone Graft is a promising method of facilitating anterior intervertebral spinal fusion, decreasing pain, and improving clinical outcomes in patients who have undergone anterior lumbar fusion surgery with structural threaded cortical allograft bone dowels.

Topics: Adult; Aged; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Transplantation; Collagen; Diskectomy; Drug Carriers; Drug Implants; Female; Humans; Ilium; Intervertebral Disc Displacement; Low Back Pain; Lumbar Vertebrae; Male; Middle Aged; Osteogenesis; Prospective Studies; Recombinant Proteins; Spinal Fusion; Tomography, X-Ray Computed; Transforming Growth Factor beta; Treatment Outcome

A prospective randomized clinical study was conducted.. To determine whether the dose and carrier that were successful in rhesus monkeys could induce consistent radiographic spine fusion in humans.. Preclinical studies have demonstrated that recombinant human bone morphogenetic protein-2 (rhBMP-2), an osteoinductive bone morphogenetic protein, is successful at generating spine fusion in rabbits and rhesus monkeys.. For this study, 25 patients undergoing lumbar arthrodesis were randomized (1:2:2 ratio) based on the arthrodesis technique: autograft/Texas Scottish Rite Hospital (TSRH) pedicle screw instrumentation (n = 5), rhBMP-2/TSRH (n = 11), and rhBMP-2 only without internal fixation (n = 9). On each side, 20 mg of rhBMP-2 were delivered on a carrier consisting of 60% hydroxyapatite and 40% tricalcium phosphate granules (10 cm /side). The patients had single-level disc degeneration, Grade 1 or less spondylolisthesis, mechanical low back pain with or without leg pain, and at least 6 months failure of nonoperative treatment.. All 25 patients were available for follow-up evaluation (mean, 17 months; range 12-27 months). The radiographic fusion rate was 40% (2/5) in the autograft/TSRH group and 100% (20/20) with rhBMP-2 group with or without TSRH internal fixation ( = 0.004). A statistically significant improvement in Oswestry score was seen at 6 weeks in the rhBMP-2 only group (-17.6; = 0.009), and at 3 months in the rhBMP-2/TSRH group (-17.0; = 0.003), but not until 6 months in the autograft/TSRH group (-17.3; = 0.041). At the final follow-up assessment, Oswestry improvement was greatest in the rhBMP-2 only group (-28.7, < 0.001). The SF-36 Pain Index and PCS subscales showed similar changes.. This pilot study is the first with at least 1 year of follow-up evaluation to demonstrate successful posterolateral spine fusion using a BMP-based bone graft substitute, with radiographs and CT scans as the determinant. Consistently, rhBMP-2 was able to induce bone in the posterolateral lumbar spine when delivered at a dose of 20 mg per side with or without the use of internal fixation. Patients with spondylolisthesis classified higher than Meyerding Grade 1 or with more than 5 mm of translational motion may still require internal fixation. Some patients did smoke during the postoperative period, and all in the rhBMP-2 groups still obtained solid fusions.. Consistently, rhBMP-2 with the biphasic calcium phosphate granules induced radiographic posterolateral lumbar spine fusion with or without internal fixation in patients whose spondylolisthesis did not exceed Grade 1. Statistically greater and quicker improvement in patient-derived clinical outcome was measured in the rhBMP-2 groups.

Topics: Awards and Prizes; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Substitutes; Bone Transplantation; Calcium Phosphates; Drug Implants; Female; Follow-Up Studies; Humans; Ilium; Internal Fixators; Intervertebral Disc Displacement; Low Back Pain; Lumbosacral Region; Male; Middle Aged; Pilot Projects; Prospective Studies; Recombinant Proteins; Reoperation; Spinal Fusion; Transforming Growth Factor beta; Treatment Outcome

Low back pain (LBP) is one of the top three causes of disability in developed countries, and intervertebral disc degeneration (IDD) is a major contributor to LBP. In the process of IDD, there is a gradual decrease in nucleus pulposus cells (NPCs) and extracellular matrix (ECM). Exosomes are important exocrine mediators of stem cells that can act directly on cells for tissue repair and regeneration. In this study, we determined the antisenescence, cell proliferation promotion, and ECM modulation effects of human urine-derived stem cell (USC) exosomes (USC-exos) on degenerated intervertebral discs and explored the underlying mechanism.. USCs were identified by multipotent differentiation and flow cytometry for mesenchymal stem cell- (MSC-) specific surface protein markers. USC-exos were isolated from the conditioned medium of USCs by ultracentrifugation and then analyzed by transmission electron microscopy (TEM), particle size analysis, and western blotting (WB) for exosome marker proteins. The effects of USC-exos on NPC proliferation and ECM synthesis were assessed by Cell Counting Kit-8 (CCK-8), WB, and immunofluorescence (IF) analyses. The protein differences between normal and degenerative intervertebral discs were mined, and the temporal and spatial variations in matrilin-3 (MATN3) content were determined by WB and IF in the intervertebral disc tissues. The candidate molecules that mediated the function of USC-exos were screened out and confirmed by multiple assays. Meanwhile, the mechanism underlying the candidate protein in USC-exos-induced cell proliferation and regulation of ECM synthesis promoting the activities of NPCs was explored. In addition, the effects of USC-exos on ameliorating intervertebral disc degeneration (IVD) in mice were examined by assessing computed tomography (CT), magnetic resonance imaging (MRI), and histological analyses.. The flow cytometry results showed that USCs were positive for CD29, CD44, and CD73, which are USC surface-specific markers, but negative for CD34 and CD45. In addition, USCs showed osteogenic, adipogenic, and chondrogenic differentiation potential. USC-exos exhibited a cup-shaped morphology, with a mean diameter of 49.7 ± 7.3 nm, and were positive for CD63 and TSG101 and negative for calnexin. USC-exos could promote NPC proliferation and ECM synthesis. The protein content of the matrilin family was significantly reduced in degenerative intervertebral discs, and the decrease in MATN3 was the most significant. USC-exos were found to be rich in MATN3 protein, and exosomal MATN3 was required for USC-exos-induced promotion of NPC proliferation and ECM synthesis, as well as alleviation of intervertebral disc degeneration in IVD rats. In addition, the effects of MATN3 in USC-exos were demonstrated to be achieved by activating TGF-. Our study suggests that reduced MATN3 can be considered a characteristic of intervertebral disc degeneration. USC-exos may represent a potentially effective agent for alleviating intervertebral disc degeneration by promoting NPC proliferation and ECM synthesis by transferring the MATN3 protein.

Topics: Adult; Cell Culture Techniques; Cell Proliferation; Exosomes; Humans; Intervertebral Disc Degeneration; Low Back Pain; Matrilin Proteins; Nucleus Pulposus; Stem Cells; Transforming Growth Factor beta

A retrospective cohort study.. To investigate the unknown direct costs of failed instrumented lumbar fusion using iliac crest bone graft (ICBG) and subsequent reoperation utilizing recombinant human bone morphogenetic protein-2 (rhBMP-2) from a primary payer perspective.. Recent evidence has demonstrated increased rates of instrumented lumbar fusion and utilization of rhBMP-2 to treat a range of conditions causing lower back pain. For health care providers with finite financial resources, there is an increasing demand to evaluate economic costs of available treatment modalities. The high cost of rhBMP-2 has often been cited as a leading reason for delaying its universal acceptance as a preferred substitute to ICBG. It has been hypothesized that rhBMP-2 may demonstrate cost-effectiveness if pseudarthrosis and reoperation rates are decreased, thus avoiding subsequent expenditure.. This was a retrospective cohort study of patients who underwent instrumented lumbar fusions utilizing rhBMP-2. Hospital finance records were used to calculate direct total expenditure incurred by the primary payer for the procedure using rhBMP-2. For patients who received rhBMP-2 in a secondary lumbar fusion, additional total expenditure related to the patients' failed primary instrumented fusion with ICBG was also sought.. The mean total costs associated with failed instrumented lumbar fusion using ICBG and reoperation using rhBMP-2 totaled £47,734 per patient. The total direct costs of a policy of primary instrumented lumbar fusion with rhBMP-2 were less at £26,923 per patient; however, this was not significant.. To date, this is the first study to report the costs of failed primary instrumented lumbar fusions using ICBG and subsequent secondary fusions using rhBMP-2 from a primary payer perspective. On the basis of this evidence, a policy of using rhBMP-2 in all patients undergoing a primary instrumented lumbar fusion cannot be recommended.

Topics: Bone Morphogenetic Protein 2; Bone Transplantation; Female; Health Care Costs; Hospitalization; Humans; Ilium; Low Back Pain; Male; Middle Aged; Recombinant Proteins; Reoperation; Spinal Fusion; Transforming Growth Factor beta; Treatment Failure

Recombinant human bone morphogenetic protein-2 (rhBMP-2) was recently licensed for local administration during posterior lumbar fusion. In this indication, considerable uncertainty remains about the nature and mechanisms of the many adverse effects of rhBMP-2, such as ectopic bone formation. We report a case of ectopic bone formation with impingement on a facet joint and incapacitating low back pain after minimally invasive transforaminal L5-S1 interbody fusion with local application of rhBMP-2 (InductOs(®)). Revision surgery was eventually performed to alleviate the symptoms by removing the ectopic bone. Caution is in order regarding the use of rhBMP-2 during posterior lumbar fusion. Every effort should be made to minimise the risk of complications.

Topics: Adult; Bone Morphogenetic Protein 2; Female; Humans; Low Back Pain; Lumbar Vertebrae; Ossification, Heterotopic; Recombinant Proteins; Reoperation; Spinal Fusion; Transforming Growth Factor beta

Recombinant human bone morphogenetic protein-2 (rhBMP-2) is commonly used to augment posterior and interbody spinal fusion techniques and has many reported side effects. Neuroforaminal heterotopic ossification (HO) is a known cause of postoperative leg pain, but the pathohistologic composition of this material is not well understood.. The purpose of this article was to report the histologic composition of a case of HO and lumbar radiculopathy after transforaminal lumbar interbody fusion with rhBMP-2.. This is a case report.. This is a single patient case report.. The outcomes considered were physician-recorded clinical, physiological, and functional measures.. A retrospective review of a single patient was performed. Clinical, radiographic, and pathologic specimens were reviewed and are reported.. A 69-year-old woman presented with low back pain and right leg radicular pain associated with L4-L5 stenosis and a recurrent facet cyst. After attempted nonsurgical care, she underwent an L4-L5 revision decompression with interbody and posterolateral fusions including off-label rhBMP-2. Postoperatively, her symptoms resolved for approximately 7 months but then returned in association with right L4-L5 foraminal HO. The ectopic tissue was notably larger than suggested by preoperative computed tomographic scan. It was decompressed, which then improved her symptoms. Histologic examination of the specimen revealed three discrete tissue types: a nonspecific fibrovascular stroma; immature osteoid and woven bone; and chondrocyte metaplasia with chondrocyte clustering.. Neuroforaminal HO formation is a reported side effect associated with the off-label use of rhBMP-2 for posterior lumbar interbody fusion. The mechanism of formation and the composition of this material are not well understood but may involve a chondrocyte differentiation pathway.

Topics: Aged; Bone Morphogenetic Protein 2; Chondrocytes; Female; Humans; Low Back Pain; Lumbar Vertebrae; Metaplasia; Off-Label Use; Ossification, Heterotopic; Recombinant Proteins; Recurrence; Spinal Fusion; Transforming Growth Factor beta

Topics: Bone Morphogenetic Protein 2; Erectile Dysfunction; Female; Humans; Low Back Pain; Lumbar Vertebrae; Male; Recombinant Proteins; Spinal Fusion; Transforming Growth Factor beta

Recombinant human bone morphogenetic protein-2 (rhBMP-2) promotes the induction of bone growth and is widely used in spine surgery to enhance arthrodesis. Recombinant human BMP-2 has been associated with a variety of complications including ectopic bone formation, adjacent-level fusion, local bone resorption, osteolysis, and radiculitis. Some of the complications associated with rhBMP-2 may be the result of rhBMP-2 induction of the inflammatory host response. In this paper the authors report on a patient with prior transforaminal lumbar interbody fusion (TLIF) using an interbody cage packed with rhBMP-2, in which rhBMP-2 possibly contributed to vascular injury during an attempted anterior lumbar interbody fusion. This 63-year-old man presented with a 1-year history of worsening refractory low-back pain and radiculopathy caused by a Grade 1 spondylolisthesis at L4-5. He underwent an uncomplicated L4-5 TLIF using an rhBMP-2-packed interbody cage. Postoperatively, he experienced marginal improvement of his symptoms. Within the next year and a half the patient returned with unremitting low-back pain and neurogenic claudication that failed to respond to conservative measures. Radiological imaging of the patient revealed screw loosening and pseudarthrosis. He underwent an anterior retroperitoneal approach with a plan for removal of the previous cage, complete discectomy, and placement of a femoral ring. During the retroperitoneal approach the iliac vein was adhered with scarring and fibrosis to the underlying previously operated L4-5 interbody space. During mobilization the left iliac vein was torn, resulting in significant blood loss and cardiac arrest requiring chest compression, defibrillator shocks, and blood transfusion. The patient was stabilized, the operation was terminated, and he was transferred to the intensive care unit. He recovered over the next several days and was discharged at his neurological baseline. The authors propose that the rhBMP-2-induced host inflammatory response partially contributed to vessel fibrosis and scarring, resulting in the life-threatening vascular injury during the reoperation. Spine surgeons should be aware of this potential inflammatory fibrosis in addition to other reported complications related to rhBMP-2.

Topics: Bone Morphogenetic Protein 2; Humans; Iliac Vein; Laminectomy; Low Back Pain; Lumbar Vertebrae; Male; Middle Aged; Postoperative Complications; Radiculopathy; Recombinant Proteins; Reoperation; Spinal Fusion; Spondylolisthesis; Transforming Growth Factor beta

A retrospective observational study.. To assess clinical outcomes, perioperative complications, revision surgery rates, and recombinant human bone morphogenetic protein-2 (BMP-2)-related osteolysis, heterotopic bone, and unexplained postoperative radiculitis (BMPP) in a group of patients treated with BMP-2-augmented transforaminal lumbar interbody fusion (bTLIF) for the homogeneous diagnosis of discogenic pain syndrome (DPS) and to put forth the algorithm used to make the diagnosis.. There is a paucity of literature describing outcomes of TLIF for the homogeneous diagnosis of DPS, an old but controversial member of the lumbar degenerative disease family.. The registry from a single surgeon was queried for patients who had undergone bTLIF for the homogeneous diagnosis of DPS, which was made via specific diagnostic algorithm. Clinical outcomes were determined by analyzing point improvement from typical outcome questionnaires and the data from Patient Satisfaction and Return to Work questionnaires. Independent record review was used to assess all outcomes.. Eighty percent of the cohort (36/45) completed preoperative and postoperative outcome questionnaires at an average follow-up of 41.9 ± 11.9 months, which demonstrated significant clinical improvement: Oswestry Disability Index = 16.4 (P < 0.0001), 12-Item Short Form Health Survey physical component summary score = 10.0 (P < 0.0001), and a Numeric Rating Scale for back pain = 2.3 (P < 0.0001). The median patient satisfaction score was 9.0 (10 = complete satisfaction), and 84.4% (27/32) of the cohort were able to return to their preoperative job, with or without modification. There were 3 perioperative complications, 4 revision surgical procedures, and 11 cases of benign BMPP. There were no incidents of the intraoperative dural tears or nerve root injury, and litigation involvement (11/36, P > 0.17), preoperative depression (15/36, P > 0.19) or prior discectomy/decompression (14/36, P < 0.37) was not a predictor of outcomes.. Although limited by retrospective design and small cohort, the results of this investigation suggest that bTLIF is a reasonable treatment option for patients who experience DPS and affords high patient satisfaction. A larger study is needed to confirm these findings.. 4.

Topics: Adult; Aged; Algorithms; Bone Morphogenetic Protein 2; Chronic Disease; Female; Humans; Intervertebral Disc Degeneration; Low Back Pain; Male; Middle Aged; Outcome Assessment, Health Care; Patient Satisfaction; Recombinant Proteins; Reoperation; Retrospective Studies; Spinal Fusion; Surveys and Questionnaires; Syndrome; Time Factors; Transforming Growth Factor beta; Young Adult

We collected the specimens of lumbar intervertebral disc (i.e., the symptomatic degenerative disc) from patients with discogenic low back pain to study the histopathologic features and growth factor expressions.. To study the pathogenesis of disc degeneration, meanwhile discriminating between common disc degeneration (aging disc) (i.e., black asymptomatic disc, not clinically relevant) and painful disc degeneration (i.e., symptomatic disc, clinically relevant).. The pathogenesis of intervertebral disc degeneration is poorly understood, mainly because of the difficulty to establish the experimental model with good reproducibility. Recently, the popularity of spinal fusion leads to more opportunities to obtain disc specimens, which could be applied to explore the pathogenesis of disc degeneration with modern biologic techniques.. There were 21 specimens of lumbar intervertebral discs from 15 patients with discogenic low back pain during posterior lumbar interbody fusion, 16 aging discs from patients without low back pain, and 10 normal discs as control collected for the study of their histopathologic features, as well as the expressions of basic fibroblast growth factor (bFGF) and its receptor (Flg), transforming growth factor-beta1 (TGF-beta1) and its receptor (TGF-betaRI) by immunohistochemistry. The distribution of macrophages and mast cells was also noted. Proliferating cell nuclear antigen was assessed to evaluate proliferating activities of disc cells.. The distinct histologic characteristic of the disc from the patient with discogenic low back pain was the ingrowth of vascularized granulation tissue along torn fissures, extending from the external layer of the anulus fibrosus into the nucleus pulposus. The immunohistochemical staining showed that there were strong expressions of bFGF and TGF-beta1 and their receptors, as well as a strong expression of proliferating cell nuclear antigen in the zones of granulation tissue in the painful discs. However, there were only weak expressions in the nongranulation tissue zones in the painful discs and aging discs, and no expression in the control discs. In addition, abundant macrophages and mast cells were found in the granulation tissue zones of painful discs but absent in the nongranulation tissue zones of painful discs or aging discs and the normal control discs.. The findings indicated that degeneration of the painful disc might originate from the injury and subsequent repair of anulus fibrosus. Growth factors, such as bFGF and TGF-beta1, macrophages and mast cells might play a key role in the repair of the injured anulus fibrosus and subsequent disc degeneration.

Topics: Adult; Aged; Female; Fibroblast Growth Factor 2; Filaggrin Proteins; Granulation Tissue; Humans; Immunohistochemistry; Intervertebral Disc; Intervertebral Disc Displacement; Low Back Pain; Macrophages; Magnetic Resonance Imaging; Male; Mast Cells; Middle Aged; Proliferating Cell Nuclear Antigen; Receptor, Fibroblast Growth Factor, Type 1; Receptors, Transforming Growth Factor beta; Spinal Fusion; Transforming Growth Factor beta; Transforming Growth Factor beta1

Prospective histologic comparison of perineural tissues from patients requiring decompression surgery for herniated intervertebral disc with those from cadaveric controls.. To examine the significance of herniated intervertebral-disc-associated perineural vascular and fibrotic abnormalities with respect to back pain symptom generation.. Previous cadaveric studies have demonstrated perineural vascular congestion, dilatation, and thrombosis and perineural and intraneural fibrosis occurring in association with herniated intervertebral disc. It was suggested that these neural abnormalities were the result of ischemia, due to venous outflow obstruction, and also represented a possible cause of ongoing back pain symptoms. Criticisms of such a conclusion arose, however, because the possibility could not be excluded that these abnormalities were the result of postmortem artifact.. Histologic and immunohistochemical comparison of discal and peridiscal tissues removed from 11 patients with radiographically proven herniated intervertebral disc requiring decompressive surgery and from 6 fresh cadavers without history of back pain in life.. Histology and immunohistochemistry of perineural and extraneural tissues from patients revealed vascular congestion, neovascularization, and endothelial abnormalities including luminal platelet adhesion, in association with reductions in von Willebrand factor levels, together with perivascular and perineural fibrosis. Elevated fibrogenic cytokine concentrations were also detected in patients' tissues. These changes occurred without evidence of inflammation and were absent in cadaveric control tissues.. The vascular abnormalities detected in patients may represent an important etiopathologic factor predisposing to intraneural and perineural fibrosis, and hence to chronic pain symptoms, after disc herniation. It seems important to preserve the perineural microcirculation following disc herniation.

Topics: Adult; Female; Fibrosis; Humans; Immunohistochemistry; Interleukin-1; Intervertebral Disc; Intervertebral Disc Displacement; Low Back Pain; Magnetic Resonance Imaging; Male; Middle Aged; Prospective Studies; Spinal Cord; Spinal Nerves; Tomography, X-Ray Computed; Transforming Growth Factor alpha; Transforming Growth Factor beta; von Willebrand Factor