Variation in thoracic inlet measurements and its correlation with pulmonary dysfunction in kyphoscoliotic deformities: a prospective case-control study.

BACKGROUND: Pulmonary dysfunction in thoracic kyphoscoliosis has been correlated with chest wall distortion, uneven trunk growth and restrictive pattern. The study aims to analyse the variation in thoracic inlet measurements on pulmonary dysfunction with varying curve magnitude and thoracic cage parameters. METHODS: In a non-randomised, prospective case-control study, 80 consecutive patients with thoracic kyphoscoliosis were divided into 3 groups based on Cobb angle: Group 1 (31-50), Group 2 (51-80) and Group 3 (> 80). Thoracic inlet measurement was calculated by thoracic inlet index (TI) on MRI at the sternal level. Pulmonary function and thoracic cage parameters [hemi thorax height, rib-apex distance, AP chest diameter at sternal level and transverse thoracic diameter] were documented. TI values were compared with 20 age-matched asymptomatic controls. Multivariate correlation and regression analysis were performed to investigate the correlations. RESULTS: The mean age of the study cohort was 14.1 ± 4.4 years, including Group 1 (6 patients), Group 2 (55 patients) and Group 3 (19 patients) versus 12.9 ± 2.2 years in controls. The mean TI was 2.8 ± 0.56 in Group 1, 3.7 ± 0.9 in Group 2 and 4.0 ± 1.12 in Group 3 versus 2.6 ± 0.43 in controls. Pulmonary dysfunction was severe with TI > 7.1 (p < 0.001) in Group 3 patients with thoracic hypokyphosis. Multivariate regression for thoracic parameters and TI > 5.6 showed significant correlation of pulmonary dysfunction in Group 2 and 3 curves with apex between T1 and T4, whereas transverse thoracic diameter, rib-apex distance and hemi thorax height were weakly associated. CONCLUSION: Thoracic inlet index (TI), a neglected pre-operative variable associated with pulmonary dysfunction in thoracic kyphoscoliosis, can be evaluated on MRI without an additional cost and radiation.

A Validated Score for Evaluating Spinal Instability to Assess Surgical Candidacy in Active Spinal Tuberculosis-An Evidence Based Approach and Multinational Expert Consensus Study.

STUDY DESIGN: Modified Delphi Consensus and Observational Study. OBJECTIVE: Instability in spinal tuberculosis (STB) leads to disabling spinal deformity and neurodeficit. Identifying and estimating instability remains subjective, mainly based on experience. This study aims to develop an objective scoring system to determine instability in STB. MATERIALS AND METHODS: The study included 4 phases. (1) A panel of 10 experienced spine surgeons developed a questionnaire based on literature. (2) 68 spine surgeons from 12 countries opined on the importance of each factor in a survey. Five factors deemed important by >70% of participants were further analyzed (3) 60 representative cases of STB were analyzed for instability. A preliminary scoring system was developed, a threshold score for determining instability was derived, and (4) Results were validated. RESULTS: All the 5 factors ("Spine at risk" signs, severity of vertebral body loss, Cervicothoracic/Thoracolumbar junction involvement, age ≤15, and kyphotic deformity ≥30°) considered important by >70% of participants were associated with instability and included in scoring: age ≤15 years (P-value, 0.05), cervicothoracic/thoracolumbar junction involvement (P-value, 0.028), sagittal deformity angle ratio (DAR) ≥ 15° (P-value, <.001), vertebral body loss-segmental ratio ≥.5 (P-value, <.001), and presence of spine at risk signs (P-value, <.001). A total score of ≥3/09 indicated definite instability with good sensitivity (77%) and excellent specificity (100%). Repeatability assessment showed a good agreement (.9625), and Cohen's kappa coefficient was strong (.809). CONCLUSION: A simple objective scoring system for predicting instability in STB has been developed using 5 main factors; young age, junctional involvement, severity of the deformity, vertebral body loss, and presence of spine at risk signs.

Novel Biomarkers of Health and Degeneration in Human Intervertebral Discs: In-depth Proteomic Analysis of Collagen Framework of Fetal, Healthy, Scoliotic, Degenerate, and Herniated Discs.

STUDY DESIGN: Profiling proteins expressed in the nucleus pulposus (NP) of intervertebral discs (IVDs) in five different biological states. PURPOSE: To evaluate the molecular complexity of the collagen (COL) framework and its role in the health and disease of human IVDs. OVERVIEW OF LITERATURE: Changes in COL composition have been linked to degenerative disk disease (DDD). Despite the fact that humans have 28 different types of COLs, most of the literature focuses solely on COL-1 and COL-2. This study used high-end proteomic technology to examine the entire COL composition of the human IVD across fetal (developmental-FD), normal (healthy-ND), scoliotic (early degeneration-SD), herniated (degenerate-DH), and degenerated (DD) disk phenotypes. METHODS: Forty NP tissues were snap-frozen in liquid nitrogen (-196°C) immediately before being subjected to proteomic and bioinformatic analyses from five different disk phenotypes (eight each). RESULTS: Tandem mass spectrometric analysis revealed a total of 1,050 proteins in FDs, 1,809 in ND, 1,487 in SD, 1,859 in DH, and 1,538 in the DD group. Of 28 major collagens reported in the human body, this study identified 24 different collagens with 34 subtypes in NP. Fibril-forming collagens (COL-1, 2, and 11A1) and fibril-associated collagens with interrupted triple helices (COL-9A1, 12A1, and 14A1) were abundantly expressed in FDs, representing their role in the development of NP. Multiplexin (COL-15), a hybrid proteoglycan-collagen molecule, was discovered only in FDs. Degeneration was associated with COL2A1 downregulation and COL-10A1 upregulation. CONCLUSIONS: COL10 was discovered to be a new biomarker for disk degeneration. Besides COL-1 and 2, other important COLs (6, 9, 11, 12, 14, 15) with anabolic potential and abundant expression in the fetal phenotype could be investigated for tissue engineering and novel DDD therapy.

Novel Biomarkers of Health and Degeneration in Human Intervertebral Discs: In-depth Proteomic Analysis of Collagen Framework of Fetal, Healthy, Scoliotic, Degenerate, and Herniated Discs

Methods@#Forty NP tissues were snap-frozen in liquid nitrogen (–196°C) immediately before being subjected to proteomic and bioinformatic analyses from five different disk phenotypes (eight each). @*Results@#Tandem mass spectrometric analysis revealed a total of 1,050 proteins in FDs, 1,809 in ND, 1,487 in SD, 1,859 in DH, and 1,538 in the DD group. Of 28 major collagens reported in the human body, this study identified 24 different collagens with 34 subtypes in NP. Fibril-forming collagens (COL-1, 2, and 11A1) and fibril-associated collagens with interrupted triple helices (COL-9A1, 12A1, and 14A1) were abundantly expressed in FDs, representing their role in the development of NP. Multiplexin (COL-15), a hybrid proteoglycan–collagen molecule, was discovered only in FDs. Degeneration was associated with COL2A1 downregulation and COL-10A1 upregulation. @*Conclusions@#COL10 was discovered to be a new biomarker for disk degeneration. Besides COL-1 and 2, other important COLs (6, 9, 11, 12, 14, 15) with anabolic potential and abundant expression in the fetal phenotype could be investigated for tissue engineering and novel DDD therapy.

A prospective study comparing three different all-posterior surgical techniques in the management of thoracolumbar spinal tuberculosis.

Background: Posterior only surgery has been widely performed in the treatment of thoracic and lumbar spinal tuberculosis. Surgical options include debridement with posterior instrumentation only or combined with anterior reconstruction. The aim of this study is to investigate and compare the clinical, functional and radiological outcomes using a single-stage posterior only surgery in thoracolumbar spinal tuberculosis by three different surgical techniques. Methods: Patients undergoing posterior only surgery for thoracic and lumbar spinal tuberculosis were followed up prospectively and included. Three different procedures, Group-A: Posterior instrumentation with anterior cage reconstruction (n = 49), Group-B: Posterior instrumentation and anterior autologous bone-grafting (n = 21) and Group-C: Posterior column shortening without anterior-reconstruction (n = 52) were compared for kyphosis correction achieved, kyphosis at final follow-up and degree of correction lost. Neurological assessment was done using ASIA impairment Scale(AIS) grades. Functional assessment was done using Visual analogue score (VAS), Modified McNab criteria and NASS satisfaction score. Results: A total of 122 patients were included in the study, Group-A (49), Group-B (21) and Group-C (52). Radiological correction of kyphotic deformity in anterior reconstruction, Group-A (20.17 ± 9.25°) was higher than 13.97° ± 6.06° and 14.27° ± 6.47° achieved in Groups B and C respectively. There was no significant difference in correction lost amongst the three groups (p-value, 0.76). Surgical duration, blood loss and hospital stay were significantly higher in the anterior reconstruction group (p-value, 0.001). Similarly, no significant difference was noted between the three groups in neurological and functional outcomes at 2 years. Conclusion: Posterior only approach is eminently satisfactory for treating Thoracolumbar Spinal Tuberculosis (STB). All three groups had similar functional and neurological outcomes. However there was a better correction of deformity in patients with anterior cage reconstruction.

Retraction notice to "Association between sarcoidosis and cardiovascular Outcomes: A systematic review and meta-analysis" [IJC Heart Vasculat. 41 (2022) 101073].

[This corrects the article DOI: 10.1016/j.ijcha.2022.101073.].

Are Modic changes 'Primary infective endplatitis'?-insights from multimodal imaging of non-specific low back pain patients and development of a radiological 'Endplate infection probability score'.

PURPOSE: To probe the pathophysiological basis of Modic change (MC) by multimodal imaging rather than by MRI alone. METHODS: Nineteen radiological signs found in mild infections and traumatic endplate fractures were identified by MRI and CT, and by elimination, three signs unique to infection and trauma were distilled. By ranking the Z score, radiological 'Endplate Infection Probability Score' (EIPS) was developed. The score's ability to differentiate infection and traumatic endplate changes (EPC) was validated in a fresh set of 15 patients each, with documented infection and trauma. The EIPS, ESR, CRP, and Numeric Pain Rating Scale (NRS) were then compared between 115 patients with and 80 patients without MC. RESULTS: The EIPS had a confidence of 66.4%, 83% and, 100% for scores of 4, 5 and, 6, respectively, for end plate changes suggesting infection. The mean EIPS was 4.85 ± 1.94 in patients with Modic changes compared to - 0.66 ± 0.49 in patients without Modic changes (p < 0.001). Seventy-eight (67.64%) patients with MC had a score of 6, indicating high infection possibility. There was a difference in the NRS (p < 0.01), ESR (p = 0.05), CRP (p < 0.01), and type of pain (p < 0.01) between patients with and without MC. CONCLUSION: Multimodal imaging showed many radiological signs not easily seen in MRI alone and thus missed in Modic classification. There were distinct radiological differences between EPCs of trauma and infection which allowed the development of an EIPS. The scores showed that 67.64% of our study patients with Modic changes had EPCs resembling infection rather than trauma suggesting the possibility of an infective aetiology and allowing us to propose an alternate theory of 'Primary Endplatitis'.

Association between sarcoidosis and cardiovascular Outcomes: A systematic review and Meta-analysis.

Background: Sarcoidosis is a chronic inflammatory disorder of unknown etiology associated with high morbidity and mortality. Its association with cardiovascular outcomes is under-documented. Aim: The aim of this study was to assess the adverse cardiovascular outcomes in patients with sarcoidosis compared with that of non-sarcoidosis. Methodology: Online databases including PubMed, Embase and Scopus were queried from inception until March 2022. The outcomes assessed included all-cause mortality (ACM) and incidence of ventricular tachycardia (VT), heart failure (HF) and atrial arrhythmias (AA). Result: A total of 6 studies with 22,539,096 participants (42,763 Sarcoidosis, 22,496,354 Non-Sarcoidosis) were included in this analysis. The pooled prevalence of sarcoidosis was 13.1% (95% CI 1% to 70%). The overall mean age was 47 years. The most common comorbidities were hypertension (12.7% vs 12.5%), and diabetes mellitus (5.5% vs 4%) respectively. The pooled analysis of primary endpoints showed that all-cause mortality (RR, 2.08; 95% CI: 1.17 to 3.08; p = 0.01) was significantly increased in sarcoidosis patients. The pooled analysis of secondary endpoints showed that the incidence of VT (RR, 15.3; 95% CI: 5.39 to 43.42); p < 0.001), HF (RR, 4.96; 95% CI: 2.02 to 12.14; p < 0.001) and AA (RR, 2.55; 95% CI: 1.47 to 4.44); p = 0.01) were significantly higher with sarcoidosis respectively compared to non-sarcoidosis. Conclusion: Incidence of VT, HF and AA was significantly higher in patients with CS. Clinicians should be aware of these adverse cardiovascular events associated with sarcoidosis.

Modic changes are associated with activation of intense inflammatory and host defense response pathways - molecular insights from proteomic analysis of human intervertebral discs.

BACKGROUND CONTEXT: Patients with modic changes (MC) form a distinct clinical subset with reports of higher intensity of pain, poor clinical and surgical outcomes and higher incidence of recurrence. MC also is an independent risk factor for increased post-operative surgical site infection. PURPOSE: This study aimed to investigate the biological changes at molecular level, in discs with MCs. We also aim to identify biological biomarkers and potential targets for molecular therapy. STUDY DESIGN: Experimental analysis MATERIALS AND METHODS: Nucleus pulposus (NP) from 24 patients undergoing microdiscectomy for disc herniation [14 discs with MC and 10 without modic changes (NMC)] were procured. The overall expression of proteins, biological processes, protein-protein and metabolite interactions were analysed and compared. Host defense response proteins (HDRPs) and immunological pathways activated in patients with MC were documented and analysed. RESULTS: Label-free proteomic approach with stringent filters revealed a total of 208 proteins in MC and 193 in NMC groups. 45 proteins were specific to MC; 30 to NMC and 163 common to both. Downregulated proteins in MC belonged to components of extracellular matrix such as collagens (COL- 6A1, 6A2, 6A3, 11A1, 12A1, and 20A1), and proteoglycans (versican (VCAN), and biglycan (BGN)). Inflammatory molecules [plasminogen (PLG), angiogenin (ANG), fibroblast growth factor-binding protein 2 (FGFBP2), tetranectin (CLEC3B), cartilage acidic protein 1(CRTAC1), kininogen (KNG-1), chitinase-3-like protein 2 (CHI3L2), and ferritin (FTL) were expressed only in the MC group. The significantly altered pathways in MC included Fc Fragment of IgG Receptor IIIa (FCGR3A)-mediated phagocytosis, regulation of Toll-like receptors (TLR) by endogenous ligand, neutrophil and platelet degranulation. 50 HDRPs were identified in the study, 14 of which were specific to MC and included acute phase reactants, antimicrobial peptides, complement cascade proteins, inflammatory molecule and stress response proteins. Metabolite-protein interaction analysis revealed a significant interaction between 19 proteins, specifically involving ubiquitin mediating proteasome degradative pathway and an association with the metabolite-glutamic acid in the MC group. Accumulation of glutamic acid in MC discs was confirmed by quantitative amino acid analysis using High-performance liquid chromatography. CONCLUSION: Our study confirms that MC represents an intense inflammatory status and activation of host defense response and immunological pathways. Downstream effects leading to ubiquitin mediated proteasomal degradation of ECM proteins and the resulting metabolites such as glutamic acid could cause excessive pain and needs further investigation. CLINICAL SIGNIFICANCE: We have documented the expression of inflammatory molecules, immune mechanisms and host defense response proteins which throw molecular insights into the pathological mechanisms of MC. Further, ubiquitin mediated proteasomal degradation and accumulation of glutamate in discs with MC might serve as targets for molecular therapy.

Can Scoliotic Discs Be Controls for Molecular Studies in Intervertebral Disc Research? Insights From Proteomics.

STUDY DESIGN: Proteomic analysis of human intervertebral discs. OBJECTIVES: To compare the characters of scoliotic discs and discs from magnetic resonance imaging (MRI)-normal voluntary organ donors controls used in disc research employing proteomics and establish "true controls" that can be utilized for future intervertebral disc (IVD) research. METHODS: Eight MRI-normal discs from 8 brain-dead voluntary organ donors (ND) and 8 scoliotic discs (SD) from 3 patients who underwent anterior surgery for adolescent idiopathic scoliosis were subjected to tandem mass spectrometry, and further analysis was performed. RESULTS: Mass spectrometry identified a total of 235 proteins in ND and 438 proteins in the SD group. Proteins involved in extracellular matrix integrity (Versican, keratins KRT6A, KRT14, KRT5, and KRT 13A1, A-kinase anchor protein 13, coagulation factor XIII A chain, proteoglycan 4) and proteins involved in transcription and DNA repair (Von Willebrand factor A domain-containing 3B, eukaryotic initiation factor 2B, histone H4, leukocyte cell-derived chemotaxin 2) were found to be downregulated in SD. Inflammatory proteins (C3, C1S), and oxidative stress response proteins (peroxiredoxin-2,6, catalase, myeloperoxidase, apolipoprotein E) were found to be upregulated in SD. These changes were reflected at the pathway level also. CONCLUSION: Findings of our study confirm that scoliotic discs have an abundance of inflammatory, oxidative stress response proteins, which are either absent or downregulated in the ND group indicating that scoliotic discs are not pathologically inert. Furthermore, this study has established MRI-normal discs from voluntary organ donors as the "true" control for molecular studies in IVD research.

Lumbar Disc Herniation and Preoperative Modic Changes: A Prospective Analysis of the Clinical Outcomes After Microdiscectomy.

STUDY DESIGN: Prospective comparative cohort study. OBJECTIVES: The study aims to elucidate the relationship between Modic endplate changes and clinical outcomes after a lumbar microdiscectomy. METHODS: Consecutive patients undergoing microdiscectomy for lumbar disc herniation (LDH) were prospectively studied. Pre-operative clinical and radiological parameters were recorded. The pain was assessed by Numeric pain rating scale (NPRS), and functional assessment by Oswestry Disability Index (ODI). Minimal clinically important difference (MCID) in outcome was calculated for both the groups. Complications related to surgery were studied. Follow-up was done at 6 weeks, 3 months, 6 months and 1 year. Mac Nab criteria were used to assess patient satisfaction at 1 year. RESULTS: Out of 309 patients, 86 had Modic changes, and 223 had no Modic changes. Both groups had similar back pain (p-value: 0.07) and functional scores (p-value: 0.85) pre-operatively. Postoperatively patients with Modic changes had poorer back pain and ODI scores in the third month, sixth month and 1 year (p-value: 0.001). However, MCID between the groups were not significant (p-value: 0.18 for back pain and 0.58 for ODI scores). Mac Nab criteria at 1 year were worse in Modic patients (p-value: 0.001). No difference was noted among Modic types in the pre-operative and postoperative pain and functional outcomes. Four patients in Modic group (4.7%) and one patient in the non-Modic group (0.5%) developed postoperative discitis (p-value: 0.009). CONCLUSIONS: Preoperative Modic changes in lumbar disc herniation is associated with less favorable back pain, functional scores and patient satisfaction in patients undergoing microdiscectomy.

Influence of endplate avulsion and Modic changes on the inflammation profile of herniated discs: a proteomic and bioinformatic approach.

PURPOSE: The aim of this observational radiographic and proteomic study is to explore the influence of both Modic change (MC) and endplate avulsion (EPA) on the inflammation profile of herniated discs using a proteomic and bioinformatics approach. METHODS: Fifteen nucleus pulposus (NP) harvested from surgery underwent LC-MS/MC analysis, the proteome was subsequently scanned for inflammatory pathways using a bioinformatics approach. All proteins that were identified in inflammatory pathways and Gene Ontology and present in > 7 samples were integrated in a multiple regression analysis with MC and EPA as predictors. Significant proteins were imputed in an interaction and pathway analysis. RESULTS: Compared to annulus fibrosus tear (AFT), six proteins were significantly altered in EPA: catalase, Fibrinogen beta chain, protein disulfide-isomerase, pigment epithelium-derived factor, osteoprotegerin and lower expression of antithrombin-III, all of which corresponded to an upregulation of pathways involved in coagulation and detoxification of reactive oxygen species (ROS). Moreover, the presence of MC resulted in a significant alteration of nine proteins compared to patients without MC. Patients with MC showed a significantly higher expression of clusterin and lumican, and lower expression of catalase, complement factor B, Fibrinogen beta chain, protein disulfide-isomerase, periostin, Alpha-1-antitrypsin and pigment epithelium-derived factor. Together these altered protein expressions resulted in a downregulation of pathways involved in detoxification of ROS, complement system and immune system. Results were verified by Immunohistochemistry with CD68 cell counts. CONCLUSION: Both EPA and MC status significantly influence disc inflammation. The beneficial inflammatory signature of EPA illustrates that endplate pathology does not necessarily have to worsen the outcome, but the pathological inflammatory state is dependent on the presence of MC.

Hypernatremia in the intensive care unit.

PURPOSE OF REVIEW: Hypernatremia is a relatively frequent electrolyte disorder seen in critically ill patients. As many as 27% of patients in intensive care units (ICUs) develop hypernatremia of variable severity during an ICU stay. Debate among specialists often ensues as to whether to correct hypernatremia or not. Some practitioners, particularly intensivists, believe that correction of hypernatremia with fluids may cause expansion of the extracellular fluid volume (ECFV) thereby worsening ventilation and impeding extubation. Other practitioners, including many nephrologists, do not expect correction of hypernatremia to lead to clinically apparent ECFV expansion, and fear other deleterious effects of hypernatremia. In this review we address the controversy regarding appropriate practice. RECENT FINDINGS: There are no randomized, clinical trials (RCTs) to guide the administration of electrolyte-free fluid administration in hypernatremic patients. However, there are associations, demonstrated in the literature, suggesting that hypernatremia of any severity will increase the mortality and length of stay in these patients. These associations generally support the practice of correction of hypernatremia. In addition, our knowledge of the distribution of total body water influences us towards correcting hypernatremia as an appropriate therapy. We do not expect that adequate RCTs addressing this question will be performed. SUMMARY: Allowing persistence of any degree of hypernatremia is associated with increased mortality, length of stay (LOS) and postdischarge mortality. We expect that proper use of electrolyte-free water intake will avoid adverse outcomes.

Profiling extra cellular matrix associated proteome of human fetal nucleus pulposus in search for regenerative targets.

Degeneration of the intervertebral disc is associated with a decrease in extra-cellular matrix (ECM) content due to an imbalance in anabolic and catabolic signaling. Our previous study profiled the core matrisome of fetal NP's and identified various proteins with anabolic potential for regenerative therapies. This study aims to complement those results by exploring ECM regulators, associated proteins and secreted factors of the fetal nucleus pulposus (NP). Proteomic data of 9 fetal, 7 healthy adults (age 22-79), and 11 degenerated NP's was analyzed. Based on the selection criteria, a total of 45 proteins were identified, of which 14 were uniquely expressed or upregulated in fetus compared to adult NP's. Pathway analysis with these proteins revealed a significant upregulation of one pathway and two biological processes, in which 12 proteins were involved. Prolyl 4 hydroxylase (P4HA) 1 and 2, Procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD) 1, and Heat shock protein 47 (SERPINH1) were involved in 'collagen biosynthesis' pathway. In addition, PLOD 1, SERPINH1, Annexin A1 and A4, CD109 and Galectin 3 (LGALS3) were all involved in biological process of 'tissue development'. Furthermore Annexin A1, A4 and A5, LGALS-3 and SERPINF1 were featured in 'negative regulation of cell death'. In conclusion, additionally to core ECM proteome, this study reveals ECM regulators and ECM affiliated proteins of interest to study for regenerative therapies, and their potential should be validated in future mechanistic experiments.

Subclinical infection can be an initiator of inflammaging leading to degenerative disk disease: evidence from host-defense response mechanisms.

PURPOSE: There is considerable controversy on the role of genetics, mechanical and environmental factors, and, recently, on subclinical infection in triggering inflammaging leading to disk degeneration. The present study investigated sequential molecular events in the host, analyzing proteome level changes that will reveal triggering factors of inflammaging and degeneration. METHODS: Ten MRI normal disks (ND) from braindead organ donors and 17 degenerated disks (DD) from surgery were subjected to in-gel-based label-free ESI-LC-MS/MS analysis. Bacterial-responsive host-defense response proteins/pathways leading to Inflammaging were identified and compared between ND and DD. RESULTS: Out of the 263 well-established host-defense response proteins (HDRPs), 243 proteins were identified, and 64 abundantly expressed HDRPs were analyzed further. Among the 21 HDRPs common to both ND and DD, complement factor 3 (C3) and heparan sulfate proteoglycan 2 (HSPG2) were significantly upregulated, and lysozyme (LYZ), superoxide dismutase 3 (SOD3), phospholipase-A2 (PLA2G2A), and tissue inhibitor of metalloproteinases 3 (TIMP-3) were downregulated in DD. Forty-two specific HDRPs mainly, complement proteins, apolipoproteins, and antimicrobial proteins involved in the complement cascade, neutrophil degranulation, and oxidative-stress regulation pathways representing an ongoing host response to subclinical infection and uncontrolled inflammation were identified in DD. Protein-Protein interaction analysis revealed cross talk between most of the expressed HDRPs, adding evidence to bacterial presence and stimulation of these defense pathways. CONCLUSIONS: The predominance of HDRPs involved in complement cascades, neutrophil degranulation, and oxidative-stress regulation indicated an ongoing infection mediated inflammatory process in DD. Our study has documented increasing evidence for bacteria's role in triggering the innate immune system leading to chronic inflammation and degenerative disk disease.

The catastrophization effects of an MRI report on the patient and surgeon and the benefits of 'clinical reporting': results from an RCT and blinded trials.

PURPOSE: Inappropriate use of MRI leads to increasing interventions and surgeries for low back pain (LBP). We probed the potential effects of a routine MRI report on the patient's perception of his spine and functional outcome of treatment. An alternate 'clinical reporting' was developed and tested for benefits on LBP perception. METHODS: In Phase-I, 44 LBP patients were randomized to Group A who had a factual explanation of their MRI report or Group B, who were reassured that the MRI findings showed normal changes. The outcome was compared at 6 weeks by VAS, PSEQ-2, and SF-12. In Phase-II, clinical reporting was developed, avoiding potential catastrophizing terminologies. In Phase-III, 20 MRIs were reported by both routine and clinical methods. The effects of the two methods were tested on four categories of health care professionals (HCP) who read them blinded on their assessment of severity of disease, possible treatment required, and the probability of surgery. RESULTS: Both groups were comparable initial by demographics and pain. After 6 weeks of treatment, Group A had a more negative perception of their spinal condition, increased catastrophization, decreased pain improvement, and poorer functional status(p = significant for all). The alternate method of clinical reporting had significant benefits in assessment of lesser severity of the disease, shift to lesser severity of intervention and surgery in three groups of HCPs. CONCLUSION: Routine MRI reports produce a negative perception and poor functional outcomes in LBP. Focussed clinical reporting had significant benefits, which calls for the need for 'clinical reporting' rather than 'Image reporting'.

Current updates in management of extremity injuries in polytrauma.

Injury-related morbidity and mortality have been one of the most common causes of loss in productivity across all geographic distributions. It remains to be a global concern despite a continual improvement in regional and national safety policies. The establishment of trauma care systems and advancements in diagnostics and management have improved the overall survival of severely injured. A better understanding of the physiopathological and immunological responses to injury led to a significant shift in trauma care from "Early Total Care" to "Damage Control Orthopedics." While most of these algorithms were tailored to the philosophy of "life before limb," the impact of improper fracture management on disability and societal loss is increasingly being recognized. Recently, "Early Appropriate Care" of extremities has gained importance; however, its implementation is influenced by regional health care policies, available resources, and expertise and varies between low and high-income countries. A review of the literature was performed using PubMed, Embase, Web of Science, and Scopus databases on articles published from 1990 to 2020 using the Mesh terms "Polytrauma," "Multiple Trauma," and "Fractures." This review aims to consolidate on guidelines and available evidence in the management of extremity injuries in a polytraumatized patient to achieve better clinical outcomes of these severely injured.

Management of pelvic injuries in hemodynamically unstable polytrauma patients - Challenges and current updates.

Pelvic injuries are notorious for causing rapid exsanguination, and also due to concomitant injuries and complications, they have a relatively higher mortality rate. Management of pelvic fractures in hemodynamically unstable patients is a challenging task and has been variably approached. Over the years, various concepts have evolved, and different guidelines and protocols were established in regional trauma care centers based mainly on their previous experience, outcomes, and availability of resources. More recently, damage control resuscitation, pelvic angioembolization, and acute definitive internal fixation are being employed in the management of these unstable injuries, without clear consensus or guidelines. In this background, we have performed a computerized search using the Cochrane Database of Systematic Reviews, Scopus, Embase, Web of Science, and PubMed databases on studies published over the past 30 years. This comprehensive review aims to consolidate available literature on the current epidemiology, diagnostics, resuscitation, and management options of pelvic fractures in polytraumatized patients with hemodynamic instability with particular focus on damage control resuscitation, pelvic angioembolization, and acute definitive internal fixation.

Uncovering molecular targets for regenerative therapy in degenerative disc disease: do small leucine-rich proteoglycans hold the key?

BACKGROUND CONTEXT: Small leucine-rich proteoglycans (SLRPs) play an essential role in extracellular matrix (ECM) organization and function. Recently, dysregulation of SLRPs has been implicated in degenerative disc disease (DDD). An in-depth analysis using high-throughput proteomic sequencing might provide valuable information on their implications in health and disease. PURPOSE: To utilize proteomics for analyzing the expression of SLRPs in fetal, healthy adult, and degenerated discs, to identify possible molecular targets to halt or reverse the degenerative process. STUDY DESIGN: Experimental analysis. METHODS: Proteomic signatures of 8 magnetic resonance imaging (MRI) normal lumbar discs (ND) [harvested from brain dead alive organ donors] were compared to 8 fetal disc samples (FD) [harvested from fetal spines devoid of congenital anomalies following spontaneous or medical termination of pregnancy] and 8 degenerate discs (DD) [collected from patients undergoing fusion surgery]. The various functional pathways along with the differential expression of SLRPs and the associated changes in collagens, large proteoglycans (LLRPs), matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) have been analyzed further using bioinformatics. This project was self-funded by the Ganga Orthopedic Research and Education Foundation. RESULTS: ESI-LC-MS/MS analysis revealed a total of 1,029 proteins in FD, 1,785 proteins in ND, and 1,775 proteins in DD. Fetal disc proteins were engaged mainly in ribosomal pathways (indicating active proliferation and regenerative potential). The healthy adult discs (ND) primarily participated in ECM maintenance and basic metabolic pathways, whereas the unique proteins of DD group were involved in inflammatory (Complement and coagulation cascades, Systemic Lupus Erythematosus and Leukocyte transendothelial migration) pathways and infective (Staphylococcus aureus infection, Prion diseases, Amoebiasis, Pertussis, and Legionellosis) channels which favor the recent concepts of inflammaging and subclinical infection as causes of DDD. Analysis of SLRPs revealed the upregulation of Biglycan in FDs and downregulation of Lumican, Decorin, Prolargin, and Chondroadherin in the DD group. The universal decrease in the abundance of SLRPs in the DD group was associated with an increase in MMPs and a reduction in TIMPs, collagen and LLRP content. CONCLUSIONS: Our study documents the influence of SLRPs in the maintenance of disc health and also the need for future research in using them for disc regeneration. CLINICAL SIGNIFICANCE: The various SLRPs that we identified are all known to have a beneficial influence on ECM integrity and a negative effect on the degenerative process at different stages in the evolution of degeneration. Biglycan, which is abundantly present in a fetus, may be suitable for regenerative therapy, and the other SLRPs like Lumican, Prolargin, Decorin, and Chondroadherin may serve the same purpose and/or as biomarkers.

Presence of preoperative Modic changes and severity of endplate damage score are independent risk factors for developing postoperative surgical site infection: a retrospective case-control study of 1124 patients.

PURPOSE: There is increasing evidence of an association between Modic changes (MC) and subclinical infection. However, the association of MC with postoperative surgical site infection (SSI) has not been adequately probed. This study primarily aimed to investigate a probable association between preoperative MC, total endplate damage score (TEPS), and SSI. METHODS: A retrospective analysis of 1124 patients who underwent surgery in a single institution (2016-2018) was performed, using both univariate and multiple logistic regression analyses to identify independent risk factors for SSI. RESULTS: The prevalence of SSI was 4% (44/1124 patients), with no association with age or sex. The prevalence of MC in the SSI group was significantly higher-79.54% (35/44) compared to 58.79% (635/1080) (p value = 0.006) in the control group with no specific relation to type or location of MC. A higher TEPS was associated with SSI (p value = 0.009). A receiver operating characteristic (ROC) curve for TEPS values to assess predictiveness of SSI showed TEPS ≥ 5.5 to have a better sensitivity of 84% than 72% for a TEPS ≥ 6.5. Univariate analysis showed TEPS > 6 (odds ratio 3.887) to have a stronger association with SSI than the presence of MC (odds ratio 2.725). Among various types of surgeries, discectomy had a higher association with SSI (p value = 0.03) when compared to fusion (p value = 0.071). However, multiple logistic regression analysis revealed only TEPS > 6, presence of MC and hypothyroidism as independent risk factors for SSI. CONCLUSION: Our data suggest that preoperative MC and TEPS > 6 are independent risk factors for developing surgical site infections. MC could be foci of chronic subclinical infection and not mere markers of degeneration, as initially described.