Injectable butyrate-prodrug micelles induce long-acting immune modulation and prevent autoimmune arthritis in mice.

Short chain fatty acid (SCFAs), such as butyrate, have shown promising therapeutic potential due to their immunomodulatory effects, particularly in maintaining immune homeostasis. However, the clinical application of SCFAs is limited by the need for frequent and high oral dosages. Rheumatoid arthritis (RA) is characterized by aberrant activation of peripheral T cells and myeloid cells. In this study, we aimed to deliver butyrate directly to the lymphatics using a polymeric micelle-based butyrate prodrug to induce long-lasting immunomodulatory effects. Notably, negatively charged micelles (Neg-ButM) demonstrated superior efficacy in targeting the lymphatics following subcutaneous (s.c.) administration and were retained in the draining lymph nodes, spleen, and liver for over one month. In the collagen antibody-induced arthritis (CAIA) mouse model of RA, only two s.c. injections of Neg-ButM successfully prevented disease onset and promoted tolerogenic phenotypes in T cells and myeloid cells, both locally and systemically. These results underscore the potential of this strategy in managing inflammatory autoimmune diseases by directly modulating immune responses via lymphatic delivery.

3-D Printed Skull Model: Role in Identification of Site of Bone Defect in Cases with CSF Rhinorrhea.

Role of 3-D models in the identification of the site and extent of bone defects in the skull base for the treatment of CSF rhinorrhea is analyzed. Such models were used successfully in the management of two patients who failed previous attempts at basal reconstruction. The principal advantage of the models was in exact delineation of the size and site of bone defect and deciphering of its relationship with adjoining critical regions of the brain.

A serine-conjugated butyrate prodrug with high oral bioavailability suppresses autoimmune arthritis and neuroinflammation in mice.

Butyrate-a metabolite produced by commensal bacteria-has been extensively studied for its immunomodulatory effects on immune cells, including regulatory T cells, macrophages and dendritic cells. However, the development of butyrate as a drug has been hindered by butyrate's poor oral bioavailability, owing to its rapid metabolism in the gut, its low potency (hence, necessitating high dosing), and its foul smell and taste. Here we report that the oral bioavailability of butyrate can be increased by esterifying it to serine, an amino acid transporter that aids the escape of the resulting odourless and tasteless prodrug (O-butyryl-L-serine, which we named SerBut) from the gut, enhancing its systemic uptake. In mice with collagen-antibody-induced arthritis (a model of rheumatoid arthritis) and with experimental autoimmune encephalomyelitis (a model of multiple sclerosis), we show that SerBut substantially ameliorated disease severity, modulated key immune cell populations systemically and in disease-associated tissues, and reduced inflammatory responses without compromising the global immune response to vaccination. SerBut may become a promising therapeutic for autoimmune and inflammatory diseases.

Adult idiopathic de novo lumbar scoliosis: Analysis of surgical treatment in 14 patients by "only fixation".

OBJECTIVE: The authors report their experience with 14 cases having adult idiopathic de novo lumbar scoliosis (AIDLS) and presenting with the predominant symptoms of claudication pain in the low back and legs. The patients were treated by only multisegmental stabilization, and the surgical procedure aimed for arthrodesis without any form of bone or soft-tissue decompression. The clinical outcome of this novel form of surgical treatment is presented. MATERIALS AND METHODS: During the period of June 2014 to June 2019, 14 patients having AIDLS (degenerative scoliosis) were surgically treated. Apart from clinical and radiological guides, instability was diagnosed on the basis of direct physical observation of the status of articulation and by manual manipulation of bones of the region. The Camille transarticular facet screw fixation technique provided a quick, safe, and strong segmental spinal fixation. An additional inter-screw metal link plate provided intersegmental stability at selected levels. The Oswestry Disability index and visual analog scale were used to assess the patients before and after surgery and at follow-up. In addition, a personalized Patient Satisfaction Score was used to assess the outcome of surgery. RESULTS: Clinical symptomatic recovery was observed in all patients in the immediate postoperative period. During the average follow-up period, 100% patients had varying degrees of symptomatic relief. CONCLUSIONS: Spinal instability is the nodal point of pathogenesis of spinal degeneration-related AIDLS. Only fixation of the involved spinal segments is necessary, and decompression by bone or soft-tissue resection is not necessary.

Chiari 1 Formation Redefined-Clinical and Radiographic Observations in 388 Surgically Treated Patients.

OBJECTIVE: The subject of Chiari formation is revisited and redefined. Results of surgical treatment of patients with Chiari formation by atlantoaxial fixation are presented. METHODS: Results were analyzed of 388 patients with Chiari formation surgically treated during 2010 to June 2019. RESULTS: Two hundred and sixty-six patients had syringomyelia. Two hundred and three patients had no craniovertebral bone abnormality and 74 patients had group A and 111 patients had group B basilar invagination. Twenty-nine patients had been earlier treated by foramen magnum decompression surgery with or without duroplasty. Clinical parameters, analysis of video recordings both before and after surgery, and patient self-assessment were included in the analysis of outcome. Immediate postoperative and sustained clinical improvement was observed in 385 patients (99.4%). CONCLUSIONS: Satisfactory clinical outcome in most patients after atlantoaxial fixation and without any manipulation of neural structures, dura, or bone in the region of foramen magnum consolidates the viewpoint that atlantoaxial instability is the nodal point of pathogenesis of Chiari 1 formation. The study suggests that Chiari 1 formation may be a secondary natural neural alteration in the face of atlantoaxial instability. The role of foramen magnum decompression surgery needs to be reassessed.

Cervical spondylosis in patients presenting with "severe" myelopathy: Analysis of treatment by multisegmental spinal fixation - A case series.

BACKGROUND: Surgical strategy of multisegmental spinal fixation that includes atlantoaxial joint for patients having cervical spondylosis-related symptoms of severe myelopathy is analyzed. OBJECTIVE: Surgical outcome of patients presenting with "severe" symptoms of cervical myelopathy having multisegmental degenerative cervical spondylosis and treated by multisegmental spinal fixation is analyzed. Atlantoaxial joint was included in the fixation construct in majority of patients. No bone, soft tissue, osteophyte, or disc resection for decompression was done. MATERIALS AND METHODS: Sixty-four patients having multisegmental cervical spondylosis who presented with symptoms of severe myelopathy were surgically treated during the period from March 2013 to December 2018. On the basis of the concept that instability is the primary cause of spinal degeneration, multisegmental spinal fixation was done in all patients. Atlantoaxial joint was included in the fixation construct in 48 patients. The levels of spinal fixation were determined on the basis of direct observation of facet joints and by manual manipulation and were guided by the presenting clinical features and radiological information. Clinical monitoring was done using Goel clinical grading, modified Japanese Orthopedic Association Score, and visual analog score parameters. Patient satisfaction index assessed the functional and symptomatic improvement. RESULTS: During the follow-up that ranged from 6 to 75 months, all patients improved in their clinical status. Fifty-five (85.9%) patients could walk independently or with mild support. CONCLUSIONS: Multisegmental spinal fixation that includes atlantoaxial joint in most patients forms a rational treatment strategy for patients of cervical spondylosis presenting with severe symptoms of myelopathy.

Revision for Failed Craniovertebral Junction Stabilization: A Report of 30 Treated Cases.

OBJECTIVE: To analyze the probable causes of failed craniovertebral junction stabilization procedures, and to evaluate the advantages of the Goel technique in revision surgery and the positive factors that lead to reduction of the instability and achieve ultimate arthrodesis. METHODS: During the period from January 2010 to June 2018, we treated 30 cases where previous attempt at craniovertebral stabilization with various fixation techniques had failed and the patients presented with progressively worsening neurologic deficits. All patients were re-operated by lateral mass fixation techniques described by the senior author. The technique involved opening of the atlantoaxial joint, denuding the articular cartilage, introduction of bone graft within the articular cavity, and plate and screw fixation. No bone decompression was done. RESULTS: Fixation of multiple subaxial spinal segments (n = 9), inclusion of occipital bone in the fixation construct (n = 21), and dependence on metal stabilization rather than bone fusion (n = 19) appear to be important causes of implant failure. All patients improved in clinical symptoms after revision surgery. Postoperative images of all patients demonstrated significant reduction of the atlantoaxial dislocation and craniovertebral junction realignment. During the average follow-up period of 32 months, all reoperated patients continued to show clinical recovery. No further surgery was necessary. CONCLUSIONS: Although relatively difficult, when indicated, reoperation and direct stabilization of the atlantoaxial joint can result in significant and enduring clinical recovery.

Central or Axial Atlantoaxial Dislocation as a Cause of Cervical Myelopathy: A Report of Outcome of 5 Cases Treated by Atlantoaxial Stabilization.

OBJECTIVE: The implications of diagnosis and treatment of central or axial atlantoaxial dislocation (CAAD) as a cause of symptoms of cervical myelopathy are evaluated. METHODS: This is a report of a series of 5 patients who presented with the primary symptoms of spasticity and motor weakness and paresthesias in all the limbs. There was no evidence of any significant compression of the dural tube or neural structures at the craniovertebral junction. There was no craniovertebral junction instability when assessed by classically described radiologic parameters. CAAD was diagnosed based on our recently discussed parameter of facetal alignment, corroborative clinical and radiologic evidence, and direct observation of atlantoaxial instability by manual manipulation of the bones of the region. All patients underwent atlantoaxial fixation. RESULTS: There was remarkable improvement in the clinical symptoms in the immediate postoperative period and during the follow-up period of 12-24 months (average, 16 months). All patients have continued to have progressive clinical recovery. Clinical assessments were done using Goel clinical evaluation scale, Japanese Orthopedic Association score, and visual analog scale. CONCLUSIONS: Identification and treatment of CAAD can have a significant management impact on patients where the cause of spastic quadriparesis is otherwise undiagnosed.

Multilevel Spinal Segmental Fixation for Kyphotic Cervical Spinal Deformity in Pediatric Age Group-Report of Management in 2 Cases.

OBJECTIVE: We discuss the role of instability of multiple spinal segments including the atlantoaxial joint in the pathogenesis of cervical kyphotic deformity. MATERIAL AND METHODS: Two male patients (5 and 17 years old) had severe cervical kyphosis and presented with symptoms related to myelopathy. The patients underwent multisegmental spinal distraction and fixation that included atlantoaxial joint. No bone decompression was done. RESULTS: At a follow-up of >30 months, both patients had significant neurologic recovery. Investigations at follow-up showed successful arthrodesis of treated spinal segments. Although incomplete, there was recovery in kyphosis. CONCLUSIONS: Multisegmental spinal distraction and fixation can lead to reduction in kyphosis and relief from symptoms related to myelopathy. Role of spinal instability in general and atlantoaxial joint instability in particular in pathogenesis of cervical kyphosis need to be assessed on the basis of studies with a larger number of patients.

Nerve root anomalies detected intra-operatively technical nuances towards achieving a successful surgical outcome: our experience of three case reports at a tertiary level centre.

OBJECTIVE: Analysis of three case reports of nerve root anomalies detected intra-operatively and its implications. DESIGN: Data collected during one year prospective non-randomised study using hospital records. SETTING: Single tertiary care centre. SUBJECTS: 3 patients in one year period.

Internal decompression for spinal stenosis (IDSS) for decompression and use of interlaminar dynamic device (CoflexTM) for stabilization in the surgical management of degenerative lumbar canal stenosis with or without mild segmental instability: our initial results.

INTRODUCTION: Internal decompression of spinal stenosis (IDSS) and Posterior dynamic stabilization (PDS) form a bridge between decompression laminectomy alone and rigid fusion, by attempting to sustain beneficial effects of decompression and stabilization in an attempt to prevent bad effects of relentless degeneration. OBJECTIVE: To evaluate the clinical outcome in operated patient of posterior dynamic stabilization. DESIGN: Data were collected over 1 year in prospective, nonrandomized follow-up study using outcome scales. SETTING: Single surgeon, tertiary care centre in Mumbai, India. Described here is the operative technique of posterior dynamic stabilization using CoFlexTM and clinical outcome of 67 consecutive patients using Visual Analogue Scale and Oswestry Disability Score.

Software version of Roland Morris Disability questionnaire for outcome assessment in low back pain.

BACKGROUND: Developing and using the software version of existing validated paper version of patient-related outcome can go a long way in saving cost, time and effort. However, the equivalence of paper version and software versions cannot be assumed. The aim of the study is to test the equivalence between paper version and software version of Roland Morris Disability Questionnaire and its acceptability among patients. METHODS: This is a within-subject cross over equivalence study. Fifty-five patients with back pain were asked to complete the paper and software version of RMDQ in random order. Patients were included from the Neuro Spinal surgery outpatient department of Lilavati Hospital and Research Center. RESULTS: Statistical analysis of 52 patients who completed the study showed high agreement between the paper and software version of the questionnaire (intraclass correlation coefficient 0.994, 95% confidence interval (0.989-0.996)). High sensitivity and specificity of 84 and 88% of the software version was noted. About 69.2% patients preferred software version over paper version. CONCLUSION: Our study shows that software version is comparable to the paper version. It may prove to be a useful tool for epidemiological studies and patient follow-up over longer period.

Approaches to paraspinal tumours - a technical note.

Neurogenic tumours of the paraspinal space can occur in all age groups. It is common in adult population and relatively rare in elderly group. Usually they are benign, but in children, arising from the autonomic system, tends to be malignant in nature. Usually in adults, they arise from peripheral nerve sheath and are labelled as schwannomas. For a given tumour, determination of a correct surgical approach is mandatory to achieve a successful surgical outcome. Several factors like tumour size, histology, involvement of the bony spinal canal, etc. are some of the deciding factors for a correct surgical approach. Since many such tumours are benign, total excision is possible with a correct surgical approach. If the tumour involves the integrity of the spine then additionally a stabilization procedure may have to be carried out. Unfortunately, there are still no guidelines regarding the choice of surgical approach for the excision of such tumors. Presented here is a series of five patients managed by us over a period of 10 years. Four patients were adults and one female child was three years old. Four patients were operated upon successfully and the fifth one is waiting for surgery.

Multilevel Spinal Stabilization as a Treatment for Hirayama Disease: Report of an Experience with Five Cases.

OBJECTIVE: To analyze the role of multisegmental spinal instability in the pathogenesis of Hirayama disease. MATERIAL AND METHODS: From June 2014 to January 2016, the authors managed 5 patients with Hirayama disease. The patients were diagnosed on the basis of classical described radiologic and clinical guidelines. All 5 patients were treated with multilevel cervical fixation that included fixation of the atlantoaxial joint in 4 patients by the adoption of the facetal fixation methods. No dural or bone decompression was performed. The follow-up ranged from 7 to 26 months (average 17.6 months). RESULTS: The most remarkable feature was an immediate postoperative and progressive improvement in the symptoms of weakness, wasting, and deformity of hands in all patients. The other remarkable feature was an immediate postoperative reduction in extradural mass in all patients and its complete disappearance in 2 patients. CONCLUSIONS: From the observations, it appears that atlantoaxial and subaxial spinal instability plays a major role in the pathogenesis of Hirayama disease.

Chiari malformation: Has the dilemma ended?

Chiari malformation as a clinical entity has been described more than hundred years ago. The concepts regarding pathogenesis, clinical features and management options have not yet conclusively evolved. Considering that a variety of treatment methods are being adopted to treat Chiari malformation is suggestive of the fact that confusion still reigns supreme in the minds of treating clinicians. Over the years, the understanding of Chiari malformation has changed from a disease process to a natural protective phenomenon and the treatment from decompression to fixation.