Genomic investigation of bone tuberculosis highlighted the role of subclinical pulmonary tuberculosis in transmission.

BACKGROUND: Extrapulmonary tuberculosis (EPTB) without symptomatic pulmonary involvement has been thought to be non-transmissible, but EPTB with asymptomatic pulmonary tuberculosis (PTB) could transmit tuberculosis (TB). Genomic investigation of Mycobacterium tuberculosis (Mtb) isolates from EPTB may provide insight into its epidemiological role in TB transmission. METHODS: Between January 2017 and May 2020, 107 Mtb isolates were obtained from surgical drainage of bone TB patients at the Beijing Chest Hospital, and 218 Mtb strains were isolated from PTB cases. These 325 Mtb isolates were whole-genome sequenced to reconstruct a phylogenetic tree, identify transmission clusters, and infer transmission links using a Bayesian approach. Possible subclinical PTB in the bone TB patients was investigated with chest imaging by two independent experts. RESULTS: Among 107 bone TB patients, 10 were in genomic clusters (≤12 SNPs). Phylogenetic analysis suggested that three bone TB patients transmitted the infection to secondary cases, supported by epidemiological investigations. Pulmonary imaging of 44 bone TB patients revealed that 79.5 % (35/44) had radiological abnormalities suggestive of subclinical PTB. CONCLUSIONS: This study provides genomic evidence that bone TB patients without clinically diagnosed PTB can be sources of TB transmission, underscoring the importance of screening for subclinical, transmissible PTB among EPTB cases.

Recent Advances in Nanotechnology-Based Strategies for Bone Tuberculosis Management.

Bone tuberculosis, an extrapulmonary manifestation of tuberculosis, presents unique treatment challenges, including its insidious onset and complex pathology. While advancements in anti-tubercular therapy have been made, the efficacy is often limited by difficulties in achieving targeted drug concentrations and avoiding systemic toxicity. The intricate bone structure and presence of granulomas further impede effective drug delivery. Nano-drug delivery systems have emerged as a promising alternative, offering the enhanced targeting of anti-tubercular drugs. These systems, characterized by their minute size and adaptable surface properties, can be tailored to improve drug solubility, stability, and bioavailability, while also responding to specific stimuli within the bone TB microenvironment for controlled drug release. Nano-drug delivery systems can encapsulate drugs for precise delivery to the infection site. A significant innovation is their integration with prosthetics or biomaterials, which aids in both drug delivery and bone reconstruction, addressing the infection and its osteological consequences. This review provides a comprehensive overview of the pathophysiology of bone tuberculosis and its current treatments, emphasizing their limitations. It then delves into the advancements in nano-drug delivery systems, discussing their design, functionality, and role in bone TB therapy. The review assesses their potential in preclinical research, particularly in targeted drug delivery, treatment efficacy, and a reduction of side effects. Finally, it highlights the transformative promise of nanotechnology in bone TB treatments and suggests future research directions in this evolving field.

Imaging of musculoskeletal tuberculosis.

Extra-pulmonary tuberculosis (TB) of the musculoskeletal system usually manifests with non-specific clinical features, mimicking a variety of diseases. Diagnosis and treatment of spinal and extra-spinal musculoskeletal TB are often challenging. Imaging has an important role in detecting this disease, aiding diagnosis, identifying complications, and monitoring disease progression. Radiographs and magnetic resonance imaging are the key imaging modalities utilized. Radiologists should aim to be familiar with the spectrum of imaging features of TB affecting spinal and extra-spinal locations in the musculoskeletal system.

Comparison of Autografts and Biodegradable 3D-Printed Composite Scaffolds with Osteoconductive Properties for Tissue Regeneration in Bone Tuberculosis.

Tuberculosis remains one of the major health problems worldwide. Besides the lungs, tuberculosis affects other organs, including bones and joints. In the case of bone tuberculosis, current treatment protocols include necrectomy in combination with conventional anti-tuberculosis therapy, followed by reconstruction of the resulting bone defects. In this study, we compared autografting and implantation with a biodegradable composite scaffold for bone-defect regeneration in a tuberculosis rabbit model. Porous three-dimensional composite materials were prepared by 3D printing and consisted of poly(ε-caprolactone) filled with nanocrystalline cellulose modified with poly(glutamic acid). In addition, rabbit mesenchymal stem cells were adhered to the surface of the composite scaffolds. The developed tuberculosis model was verified by immunological subcutaneous test, real-time polymerase chain reaction, biochemical markers and histomorphological study. Infected animals were randomly divided into three groups, representing the infection control and two experimental groups subjected to necrectomy, anti-tuberculosis treatment, and plastic surgery using autografts or 3D-composite scaffolds. The lifetime observation of the experimental animals and analysis of various biochemical markers at different time periods allowed the comparison of the state of the animals between the groups. Micro-computed tomography and histomorphological analysis enabled the evaluation of osteogenesis, inflammation and cellular changes between the groups, respectively.

Metabolic switching and cell wall remodelling of Mycobacterium tuberculosis during bone tuberculosis.

OBJECTIVES: Bone tuberculosis (TB) is the third most common types of extrapulmonary tuberculosis. It is critical to understand mycobacterial adaptive strategies within bone lesions to identify mycobacterial factors that may have role in disease pathogenesis. METHODS: Whole genome microarray was used to characterize the in-vivo transcriptome of Mycobacterium tuberculosis (M.tb) within bone TB specimens. Mycobacterial virulent proteins were identified by bioinformatic software. An in vitro osteoblast cell line model was used to study the role of these proteins in bone TB pathogenesis. RESULTS: 914 mycobacterial genes were significantly overexpressed and 1688 were repressed in bone TB specimens. Pathway analysis of differentially expressed genes demonstrated a non-replicative and hypometabolic state of M.tb, reinforcement of the mycobacterial cell wall and induction of DNA damage repair responses, suggesting possible survival strategies of M.tb within bone. Bioinformatics mining of microarray data led to identification of five virulence proteins. The genes encoding these proteins were also upregulated in the in vitro MC3T3 osteoblast cell line model of bone TB. Further, exposure of osteoblast cells to two of these virulence proteins (Rv1046c and Rv3663c) significantly inhibited osteoblast differentiation. CONCLUSION: M.tb alters its transcriptome to establish infection in bone by upregulating certain virulence genes which play a key role in disturbing bone homeostasis.

Bone tuberculosis, in patients with no prior history of tuberculosis.

There are different types of infection caused by Mycobacterium tuberculosis, the pulmonary variety is the most common of them; infection of the bone secondary to joint replacement, is usually caused by a previous lung infection that has been disseminated. However primary bone infection is very rare and little reported, which makes information on the matter very scarce. A female patient is presented with a history of congenital hip dysplasia, who underwent multiple surgical interventions, including total hip arthroplasty (THA), afterwards she presented a fistula and persistent serous exudate; a biopsy was performed where acid-fast bacilli were detected. The delay in the diagnosis of osteoarticular tuberculosis (OATB) can lead to negative consequences, affecting the quality of life of the patient. Conventional diagnostic methods may be insufficient for the diagnosis of OATB.

Existen diferentes tipos de infección causadas por Mycobacterium tuberculosis, siendo la variedad pulmonar la más común de ellas; la infección del hueso secundaria a la artroplastia suele estar causada por una infección pulmonar previa que se ha diseminado. Sin embargo, la infección ósea primaria es muy rara y poco reportada, lo que hace que la información al respecto sea muy escasa. Se presenta un paciente femenino con antecedentes de displasia del desarrollo de la cadera, que se sometió a múltiples intervenciones quirúrgicas, incluida artroplastia total de cadera (ATC), posteriormente presentó una fístula y exudado seroso persistente; se realizó una biopsia donde se detectaron bacilos ácido-alcohol resistentes. El retraso en el diagnóstico de la tuberculosis osteoarticular (TBOA) puede tener consecuencias negativas, afectando la calidad de vida del paciente. Los métodos diagnósticos convencionales pueden ser insuficientes para el diagnóstico de TBOA.

Evaluation of Web-Based Information on Spine Tuberculosis.

OBJECTIVE: To evaluate and assess the information about spine tuberculosis available on the internet to the general public for its quality, adequacy, and authenticity. INTRODUCTION: Tuberculosis is a bacteriological disease that has been associated with humankind since early human civilization. Spinal tuberculosis is an affection of the spine by the tubercle bacilli and can cause major complications, such as neurological dysfunction and spine deformities. Since the revolution in information technology, information about the disease is widely available on the internet. MATERIAL AND METHODS: A total of 68 websites were selected on Google, Yahoo, and MSN search engines for the information available about the disease. Scientific journals, books, and any other research materials were excluded from this study. The information was documented and evaluated for its validity, sufficiency, and authorship. RESULTS: The public education websites (PEdWebs: Those websites which did not have direct involvement in patient care) were the major source of the information with 58.82% (40) of it coming from them. In all, there were 69% (47) physicians and 30.9% (21) non-physicians. Among the physicians, 89.4% reviewed the information through commercial websites. "Inadequate" information about spine tuberculosis was provided by 11.8% (8), "Moderate information" by 51.5% (35), and "Sufficient information" by 36.8 % (25) of the websites. Among the websites, 13.2% (9) did not mention any specific presentation of the disease. Sufficient information on that aspect was provided by only 45.58% (31) of the websites. Only 39% emphasized the importance of early diagnosis and subsequent disease management. The majority, i.e., 79.4% (54), did not mention the preventive measures. CONCLUSION: The internet has a lot of information regarding spine tuberculosis. The majority of this information comes from physicians. However, not every website has complete and essential information regarding the disease.

Iliac Bone Tuberculosis Presenting as Left Thigh Swelling in an Indian Female Patient: A Rare Case.

Tuberculosis (TB) is a public health issue and is one of the main contributors to morbidity and mortality. The disease is very common in endemic areas. TB mainly occurs in the lungs; however, it can spread to other organs and the same is widely reported. Cancellous bone TB like that in the iliac bone is a rare finding even in endemic areas. The pandemic of coronavirus disease (COVID-19) has resulted in the delayed reporting of many cases. The present report is of a unique case of primary iliac bone TB in an Indian female who presented with painful swelling in her left thigh for three months. A detailed clinical work-up was done to establish the diagnosis. The delay was due to COVID-19 lockdowns and management was initiated after three months. This case highlights the importance of a high degree of suspicion to diagnose TB in rare extrapulmonary sites like the iliac bone.

Tuberculosis ósea en calcáneo. Caso clínico / Bone tuberculosis in calcaneus. Clinical case

La tuberculosis extra pulmonar osteoarticular es una entidad infrecuente (16%), y aquellas de compromiso extravertebral son a su vez muy infrecuentes. Presentamos el caso clínico de un paciente masculino de 68 años de edad, con hipertensión arterial sistémica y enfermedad renal crónica, que presenta aproximadamente 1 año de evolución tórpida con dolor en retropié izquierdo, empeorando luego de infiltración con esteroide, con aumento de volumen, limitación funcional, y lesión ulcerosa con exudado purulento en cara medial. Siendo evaluado de forma clínica y con estudios de imagen por diferentes facultativos, hasta realizar toma de biopsia y cultivo óseo con diagnóstico de Tuberculosis ósea en calcáneo izquierdo. Tratado de manera quirúrgica, y actualmente cumpliendo tratamiento antituberculoso, con evolución satisfactoria recuperando movilidad articular, sin dolor y disminución del volumen de retropié(AU)

Osteoarticular extrapulmonary tuberculosis is a rare entity (16%), and those with extravertebral involvement are in turn very rare. We present the clinical case of a 68-years-old male patient with systemic arterial hypertension and chronic kidney disease, who presents approximately 1 year of torpid evolution with pain in the left hindfoot, worsening after steroid infiltration, with increased volume, limitation functional, and ulcerative lesion with purulent exudate on the medial side. He was being evaluated clinically and with imaging studies by different doctors, until taking a biopsy and bone culture with a diagnosis of Bone Tuberculosis in the left calcaneus. Surgically treated, and currently undergoing antituberculous treatment, with satisfactory evolution recovering joint mobility, without pain and decrease in rearfoot volume(AU)

Difference between the blood samples of patients with bone and joint tuberculosis and patients with tuberculosis studied using machine learning.

Background: Tuberculosis (TB) is a chronic infectious disease. Bone and joint TB is a common type of extrapulmonary TB and often occurs secondary to TB infection. In this study, we aimed to find the difference in the blood examination results of patients with bone and joint TB and patients with TB by using machine learning (ML) and establish a diagnostic model to help clinicians better diagnose the disease and allow patients to receive timely treatment. Methods: A total of 1,667 patients were finally enrolled in the study. Patients were randomly assigned to the training and validation cohorts. The training cohort included 1,268 patients: 158 patients with bone and joint TB and 1,110 patients with TB. The validation cohort included 399 patients: 48 patients with bone and joint TB and 351 patients with TB. We used three ML methods, namely logistic regression, LASSO regression, and random forest, to screen the differential variables, obtained the most representative variables by intersection to construct the prediction model, and verified the performance of the proposed prediction model in the validation group. Results: The results revealed a great difference in the blood examination results of patients with bone and joint TB and those with TB. Infectious markers such as hs-CRP, ESR, WBC, and NEUT were increased in patients with bone and joint TB. Patients with bone and joint TB were found to have higher liver function burden and poorer nutritional status. The factors screened using ML were PDW, LYM, AST/ALT, BUN, and Na, and the nomogram diagnostic model was constructed using these five factors. In the training cohort, the area under the curve (AUC) value of the model was 0.71182, and the C value was 0.712. In the validation cohort, the AUC value of the model was 0.6435779, and the C value was 0.644. Conclusion: We used ML methods to screen out the blood-specific factors-PDW, LYM, AST/ALT, BUN, and Na+-of bone and joint TB and constructed a diagnostic model to help clinicians better diagnose the disease in the future.

Multifocal bone tuberculosis simulating metastasis.

Multiple skeletal tuberculosis can be the first sign of tuberculosis. In such cases, physicians should consider tuberculosis diagnosis and take biopsies for anatomopathological evidence to make the correct diagnosis.

Notification of 6442 cases of bone tuberculosis in Brazil: epidemiological profile from 2009 to 2018 / Notificação de 6442 casos de tuberculose óssea no Brasil: perfil epidemiológico de 2009 a 2018 / Notificación de 6442 casos de tuberculosis ósea en Brasil: perfil epidemiológico de 2009 a 2018

ABSTRACT Objective: To analyze the occurrence of notified cases of bone tuberculosis in Brazil during the period from 2009 to 2018. Methods: Quantitative, descriptive and retrospective study. The data consisted of cases reported to the Notifiable Diseases Information System (SINAN) of DATASUS. To analyze the results, the non-parametric statistical Chi-squared and G tests, capable of expressing statistical associations, were used. Results: 6,442 cases of bone tuberculosis were reported in Brazil, with an average of 644.2 cases per year. The Southeast was responsible for 41.5% of the cases (n = 2676). The extrapulmonary form accounted for 87.9% (5661). There was a predominance in males (66.1%, n = 4258), Whites (41.6%, n = 2678) and in the above 35 years of age group (73.9%, n = 4757). In the data collected, the risk factor data was not correctly filled out, making reliable statistical associations impossible in this study, mainly between alcoholism, tobacco use, AIDS, diabetes, mental illness, illicit drug use and homelessness. Conclusion: There was greater notification of cases of bone tuberculosis in the Southeast and Northeast regions of Brazil, which predominantly affected young, economically productive men. Tuberculosis has a correlation with diabetes, HIV / AIDS, smoking and alcohol and drug use, according to the results of this study. Level of evidence II; Retrospective, analytical, quantitative and descriptive study.

RESUMO Objetivo: Analisar a ocorrência de casos de tuberculose óssea notificados no Brasil entre o período de 2009 a 2018. Métodos: Estudo quantitativo, descritivo e retrospectivo. Os dados consistiram em casos notificados no Sistema de Informação de Agravos de Notificação (SINAN) do DATASUS. Para análise dos resultados, foram usados testes estatísticos não paramétricos, Qui-quadrado e teste G, capazes de expressar associação estatística. Resultados: Foram notificados 6.442 casos de tuberculose óssea no Brasil, com média de 644,2 casos por ano. O Sudeste foi responsável por 41,5% dos casos (n = 2676). A forma extrapulmonar correspondeu a 87,9% (5.661). Houve predomínio no sexo masculino (66,1%, n = 4258), em brancos (41,6%, n = 2678) e maiores de 35 anos (73,9%, n = 4757). Os dados coletados não tinham preenchimento correto dos fatores de risco, o que impossibilitou a associação estatística confiável neste estudo, principalmente entre alcoolismo, tabagismo, AIDS, diabetes, doença mental, uso de drogas ilícitas e moradores de rua. Conclusões: Houve maior notificação de casos de tuberculose óssea no Sudeste e no Nordeste do Brasil, que afetou predominantemente homens jovens e em plena atividade econômica. A tuberculose tem correlação com diabetes, HIV/AIDS, tabagismo e uso de álcool e drogas ilícitas, conforme os resultados deste estudo. Nível de evidência II; Estudo retrospectivo, analítico, quantitativo e descritivo.

RESUMEN Objetivo: Analizar la ocurrencia de casos de tuberculosis ósea notificados en Brasil en el período de 2009 a 2018. Métodos: Estudio cuantitativo, descriptivo y retrospectivo. Los datos consistieron en casos notificados en el Sistema de Información de Enfermedades de Notificación (SINAN) del DATASUS. Para análisis de los resultados, fueron usados tests estadísticos no paramétricos, Chi-cuadrado y test G, capaces de expresar asociación estadística. Resultados: Fueron notificados 6.442 casos de tuberculosis ósea en Brasil, con promedio de 644,2 casos por año. El sudeste fue responsable por 41,5% de los casos (n = 2676). La forma extrapulmonar correspondió a 87,9% (5661). Hubo predominio en el sexo masculino (66,1%, n = 4258), en blancos (41,6%, n = 2678) y mayores de 35 años (73,9%, n = 4757). Los datos colectados no tenían llenado correcto de los factores de riesgo, lo que imposibilitó la asociación estadística confiable en este estudio, principalmente entre alcoholismo, tabaquismo, SIDA, diabetes, enfermedad mental, uso de drogas ilícitas y personas sin techo. Conclusiones: Hubo mayor notificación de casos de tuberculosis ósea en el sudeste y en el noreste de Brasil, que afectó predominantemente a hombres jóvenes y en plena actividad económica. La tuberculosis tiene correlación con diabetes, VIH/SIDA, tabaquismo y uso de alcohol y drogas ilícitas, conforme a los resultados de este estudio. Nivel de evidencia II; Estudio retrospectivo, analítico, cuantitativo y descriptivo.

Tuberculosis ileocecal: a propósito de un caso / Ileocecal tuberculosis: A case report

Resumen La tuberculosis es una enfermedad de importancia en la salud pública a nivel mundial, con una alta incidencia a nivel del territorio colombiano. Principalmente, afecta el parénquima pulmonar; sin embargo, en un porcentaje elevado de casos se diagnostica en su forma extrapulmonar y el tracto gastrointestinal es uno de los sitios más frecuentes. Así mismo, la región ileocecal y el íleon terminal son las regiones con más predilección por la bacteria Mycobaterium tuberculosis. Las manifestaciones en esta rara presentación de la enfermedad están dadas por dolor abdominal y sensación de masa principalmente, lesiones ulcerosas en la mucosa intestinal y hallazgos histológicos correspondientes a granulomas caseificantes de gran tamaño y de morfología confluente, que se diferencian de otras entidades como la enfermedad de Crohn. La búsqueda de la enfermedad dentro del tracto gastrointestinal se realiza con ayuda de métodos invasivos como la colonoscopia y de ayudas diagnósticas de laboratorio como cultivos, tinciones o reacción en cadena de la polimerasa (PCR). Dada la complejidad en el diagnóstico de esta forma de tuberculosis, el conocimiento y la manera en que se aborda un paciente con un cuadro sugestivo de esta enfermedad son factores importantes para establecer el manejo terapéutico oportuno. Se comparte un caso inusual de tuberculosis ileocecal como manifestación de síndrome febril prolongado con desenlace fatal.

Abstract Tuberculosis is a disease of public health importance worldwide with a high incidence in Colombia. It mainly affects the lung parenchyma. However, in a large number of cases, it is diagnosed in its extrapulmonary form, with the gastrointestinal tract being one of the most frequent sites. Mycobacterium tuberculosis has a strong predilection for the ileocecal region and the terminal ileum. Manifestations of this rare form of the disease are abdominal pain and mass sensation mainly, as well as ulcerative lesions in the intestinal mucosa and histological findings corresponding to large caseating granulomas of confluent morphology, which distinguish it from other entities such as Crohn's disease. Invasive procedures, such as colonoscopy, and diagnostic laboratory aids, such as cultures, stains, and PCR, are used to find the disease in the gastrointestinal tract. Given the difficulty of diagnosing this type of tuberculosis, knowledge and how a patient with symptoms suggestive of the disease is approached are critical factors for establishing timely treatment. The following is an unusual case of ileocecal TB as a manifestation of prolonged febrile illness with a fatal outcome.

A rare presentation of isolated carpal bone tuberculous osteomyelitis mimicking gouty arthritis.

Tuberculosis (TB) is the most prevalent infectious disease in Southeast Asia. It causes both pulmonary and extrapulmonary diseases. TB of the wrist is rare and presents as osteomyelitis or tenosynovitis. We report a middle-aged male with carpal bone tuberculous osteomyelitis. He presented with left wrist pain initially treated as gouty arthritis. Within 2 weeks, he developed seropurulent discharge with osteomyelitic changes on imaging. He underwent debridement, and intraoperatively, there was destruction of most carpal bones. Histopathological examination revealed chronic granulomatous inflammation with abscess formation. Anti-TB medication was initiated, and he made a complete recovery with almost full range of wrist movement after 9 months of treatment. This case serves as a reminder that TB is a great mimicker, and a high index of suspicion is required to make a diagnosis of TB of the wrist. Early initiation of anti-TB is pivotal to prevent complications and deterioration of joint functions.

A report of two challenging cases of bone infection: Mycobacterium tuberculosis. How to manage?

The incidence of bone tuberculosis is less than 5% of all tuberculosis cases. Furthermore, multifocal bone tuberculosis is uncommon, which rarely occurs without primary foci. It is difficult to diagnose, particularly if it is localized in both humeral heads. On the other hand, the isolated iliac bone tuberculosis is exceptional; it constitutes, also, a challenging diagnosis, which requires a high index of clinical suspicion and advanced investigations. Herein, we first report a case of multifocal tuberculosis of both humeral heads with no primary foci, and we secondarily report a case of isolated iliac bone tuberculosis. At last, however, the histological exam and polymerase chain reaction for the Mycobacterium tuberculosis complex are not always positives; they are mandatory as tests to ascertain the diagnosis.

Bone and articular impairment in tuberculosis. An important extrapulmonary involvement: a review

This is a literature review on the pathogenesis and epidemiology of bone tuberculosis (BTB). Full-text papers from 2001 to 2017 were included. After inclusion criteria were met, 23 papers were selected for analysis. Results show that in most cases of BTB, the spine is the main site involved, regardless of the geographical regions analyzed; hip and knee involvement are also frequent. These three sites are the most prevalent, totaling approximately 70 - 80% of infections. The major forms of involvement are tuberculous spondylitis, tuberculous osteomyelitis, primarily in areas of long-bone growth, as well as cases of chronic disease leading to tuberculous arthritis, mainly in endemic areas. The results also indicated that bone involvement is still prevalent, being the fifth cause of extrapulmonary disease involvement in Brazil. This review highlights the role of tuberculosis in public health, especially in economically active groups where BTB is most prevalent

Fabrication of bioactive rifampicin loaded κ-Car-MA-INH/Nano hydroxyapatite composite for tuberculosis osteomyelitis infected tissue regeneration.

Biocompatible polymers and ceramic materials have been identified as vital components to fabricate drug delivery and tissue engineering applications because of their high drug loading capability, sustained release and higher mechanical strength with remarkable in-vivo bioavailability. In the present work, initially we designed κ-carrageenan grafted with maleic anhydride and then reacted it with isoniazid drug (κ-Car-MA-INH). The polymeric system was cross linked with nanohydroxyapatite (NHAP) via electrostatic interaction followed by the addition of rifampicin (RF) and loaded to fabricate κ -Car-MA-INH/NHAP/RF nanocomposites. The chemical modification and interaction of drug with the polymeric-ceramic system were characterised by Fourier Transform Infrared spectroscopy (FT-IR). The zeta potential of the κ -Car-MA-INH/NHAP/RF nanocomposite was observed to be -20.04 mV using Zetasizer. The in vitro drug release studies demonstrated that the nanocomposite releases 76% of RF and 82% of INH in 12 days at pH 5.5. Scanning Electron Microscope analysis revealed the structural deformation of Staphylococcus aureus and Klebsiella pneumoniae upon treatment with this nanocomposite. By using ex-vivo studies combined with physio-chemical characterization methods on the erythrocytes, L929 and MG-63 cell lines, this composite was found to be biocompatible, non-cytotoxic and inducing cell proliferation with less significant hemolysis. Thus, our modified drug delivery nanocomposites afforded higher drug bioavailability with large potential for fabrication as long-acting drug delivery nanocomposites, especially with hydrophobic drugs inducing the growth of osteoblastic bone cells.

Association of the TNF-α-308, TNF-α-238 gene polymorphisms with risk of bone-joint and spinal tuberculosis: a meta-analysis.

The aim of the present study was to investigate the association of TNF-α-308 and TNF-α-238 gene polymorphisms with the risk of bone-joint and spinal tuberculosis (TB) by meta-analysis. By searching PubMed, Web of Science, Wanfang databases, CNKI, Medline, and Cochrane Library, the published articles about studies of the association of the TNF-α-308, TNF-α-238 gene polymorphisms with risk of bone-joint and spinal tuberculosis were collected by two reviewers. Begg's and Egger's tests were performed to assess publication bias. Stata 12.0 software was used for data analysis. The symmetry of the funnel plot indicated no significant publication bias in the Begg's test (A: P=1.00, B: P=0.764), and the results of the Egger's test showed no evidence of publication bias (A: P=0.954, B: P=0.626). Seven studies assessed the relationship between TNF-α-308 gene polymorphisms and risk of bone-joint and spinal tuberculosis risk. The heterogeneity (I2 ) of GG vs. AA or AG was 0% and there was no heterogeneity (χ2 = 0.06 and P=0.944) in a fixed-effects model. There was also a lack of association between TNF-α-308 polymorphism and bone-joint and spinal tuberculosis risk under the recessive model. The remaining models of the TNF-α-308 genotype and further studies of TNF-α-238 did not show a noteworthy association. Overall, there was no significant association between TNF-α-308, TNF-α-238 gene polymorphisms and bone-joint and spinal tuberculosis risk. Our study suggests that tumor necrosis factor α (TNF-α) gene polymorphisms may not contribute to bone-joint and spinal tuberculosis based on the current evidence.

A thermo-responsive and self-healing liposome-in-hydrogel system as an antitubercular drug carrier for localized bone tuberculosis therapy.

Isoniazid (INH) is a first-line therapy for bone tuberculosis (TB), but its clinic benefits are limited by severe side-effects after long-time administration. While nano-drug delivery systems present as promising strategies for INH delivery, the therapeutic efficacies are usually suboptimal due to ineffective drug accumulation at diseased sites. Local delivery system can achieve high drug concentration at focus sites with minimal systemic exposure, and herein we aimed to employ this strategy to develop a novel liposome-in-hydrogel system for localized treatment of bone TB. To achieve sustainable drug release, a derivative of INH called DINH was loaded because of its hydrophobicity, as well as its better activity and higher biosafety than INH. The hybrid system was demonstrated for thermo-responsive and self-healing properties via phase transition test and rheological studies, which were particularly useful for intra-articular administration. In vivo microdialysis studies revealed that the system can rapidly release drug into synovial fluid to reach effective inhibitory concentrations after localized injection, followed by a steady-state drug release. The optical image studies were performed to study its long-term behavior in vivo, which suggested a sustained drug release profile for several days. This work provides a promising drug delivery system for bone TB therapy.

The Epidemiology of Skeletal Tuberculosis in Northeast of Iran: A Review of 229 Cases.

BACKGROUND: The incidence of tuberculosis (TB) has increased in recent years in both developed and developing countries. Skeletal tuberculosis occurs in approximately 1% of patients with tuberculosis. The present study aimed to evaluate the epidemiology of skeletal tuberculosis in Golestan province in northeastern Iran during 2005-2014. METHODS: In the present retrospective study, the epidemiology of skeletal tuberculosis was studied in 229 skeletal tuberculosis patients who were diagnosed during 2005-2014. The prevalence rate of skeletal TB has been reported according to demographic and clinical features. RESULTS: Over the 10-year period of this study, 229 known skeletal TB cases were identified in which 56.3% were male. The mean age of the patients was 44.0±17.7 (range 7-87). All of the patients were new cases. Most of the patients (56.8%) were from the rural areas and most were diagnosed by the private healthcare system (63.8%). The highest rate of skeletal TB was seen in 2013 (15.3%). Spinal TB (81.2%) scored the highest rate and pain (96.9%) was the most prevalent symptom of skeletal TB. CONCLUSION: The findings suggest that skeletal tuberculosis in northeastern Iran should always be considered as a differential diagnosis for fever and pain on the spinal column. Due to the high level of tuberculosis in the Golestan province (Iran), further research on continued awareness of skeletal TB is stressed.