Controversies in orthopaedic oncology.

Chondrosarcoma is the second most common surgically treated primary bone sarcoma. Despite a large number of scientific papers in the literature, there is still significant controversy about diagnostics, treatment of the primary tumour, subtypes, and complications. Therefore, consensus on its day-to-day treatment decisions is needed. In January 2024, the Birmingham Orthopaedic Oncology Meeting (BOOM) attempted to gain global consensus from 300 delegates from over 50 countries. The meeting focused on these critical areas and aimed to generate consensus statements based on evidence amalgamation and expert opinion from diverse geographical regions. In parallel, periprosthetic joint infection (PJI) in oncological reconstructions poses unique challenges due to factors such as adjuvant treatments, large exposures, and the complexity of surgery. The meeting debated two-stage revisions, antibiotic prophylaxis, managing acute PJI in patients undergoing chemotherapy, and defining the best strategies for wound management and allograft reconstruction. The objectives of the meeting extended beyond resolving immediate controversies. It sought to foster global collaboration among specialists attending the meeting, and to encourage future research projects to address unsolved dilemmas. By highlighting areas of disagreement and promoting collaborative research endeavours, this initiative aims to enhance treatment standards and potentially improve outcomes for patients globally. This paper sets out some of the controversies and questions that were debated in the meeting.

NCCP-ICS joint consensus-based clinical practice guidelines on medical thoracoscopy.

ABSTRACT: Medical Thoracoscopy (MT) is commonly performed by respiratory physicians for diagnostic as well as therapeutic purposes. The aim of the study was to provide evidence-based information regarding all aspects of MT, both as a diagnostic tool and therapeutic aid for pulmonologists across India. The consensus-based guidelines were formulated based on a multistep process using a set of 31 questions. A systematic search of published randomized controlled clinical trials, open labelled studies, case reports and guidelines from electronic databases, like PubMed, EmBase and Cochrane, was performed. The modified grade system was used (1, 2, 3 or usual practice point) to classify the quality of available evidence. Then, a multitude of factors were taken into account, such as volume of evidence, applicability and practicality for implementation to the target population and then strength of recommendation was finalized. MT helps to improve diagnosis and patient management, with reduced risk of post procedure complications. Trainees should perform at least 20 medical thoracoscopy procedures. The diagnostic yield of both rigid and semirigid techniques is comparable. Sterile-graded talc is the ideal agent for chemical pleurodesis. The consensus statement will help pulmonologists to adopt best evidence-based practices during MT for diagnostic and therapeutic purposes.

Exploring Cu-Doped Co3O4 Bifunctional Oxygen Electrocatalysts for Aqueous Zn-Air Batteries.

The efficiency of oxygen electrocatalysis is a key factor in diverse energy domain applications, including the performance of metal-air batteries, such as aqueous Zinc (Zn)-air batteries. We demonstrate here that the doping of cobalt oxide with optimal amounts of copper (abbreviated as Cu-doped Co3O4) results in a stable and efficient bifunctional electrocatalyst for oxygen reduction (ORR) and evolution (OER) reactions in aqueous Zn-air batteries. At high Cu-doping concentrations (≥5%), phase segregation occurs with the simultaneous presence of Co3O4 and copper oxide (CuO). At Cu-doping concentrations ≤5%, the Cu ion resides in the octahedral (Oh) site of Co3O4, as revealed by X-ray diffraction (XRD)/Raman spectroscopy investigations and molecular dynamics (MD) calculations. The residence of Cu@Oh sites leads to an increased concentration of surface Co3+-ions (at catalytically active planes) and oxygen vacancies, which is beneficial for the OER. Temperature-dependent magnetization measurements reveal favorable d-orbital configuration (high eg occupancy ≈ 1) and a low → high spin-state transition of the Co3+-ions, which are beneficial for the ORR in the alkaline medium. The influence of Cu-doping on the ORR activity of Co3O4 is additionally accounted in DFT calculations via interactions between solvent water molecules and oxygen vacancies. The application of the bifunctional Cu-doped (≤5%) Co3O4 electrocatalyst resulted in an aqueous Zn-air battery with promising power density (=84 mW/cm2), stable cyclability (over 210 cycles), and low charge/discharge overpotential (=0.92 V).

Groundwater quality assessment using water quality index and principal component analysis in the Achnera block, Agra district, Uttar Pradesh, Northern India.

The qualitative and quantitative assessment of groundwater is one of the important aspects for determining the suitability of potable water. Therefore, the present study has been performed to evaluate the groundwater quality for Achhnera block in the city of Taj, Agra, India, where groundwater is an important water resource. The groundwater samples, 50 in number were collected and analyzed for major ions along with some important trace element. This study has further investigated for the applicability of groundwater quality index (GWQI), and the principal component analysis (PCA) to mark out the major geochemical solutes responsible for origin and release of geochemical solutes into the groundwater. The results confirm that, majority of the collected groundwater samples were alkaline in nature. The variation of concentration of anions in collected groundwater samples were varied in the sequence as, HCO3- > Cl- > SO42- > F- while in contrast the sequence of cations in the groundwater as Na > Ca > Mg > K. The Piper diagram demonstrated the major hydro chemical facies which were found in groundwater (sodium bicarbonate or calcium chloride type). The plot of Schoellar diagram reconfirmed that the major cations were Na+ and Ca2+ ions, while in contrast; major anions were bicarbonates and chloride. The results showed water quality index mostly ranged between 105 and 185, hence, the study area fell in the category of unsuitable for drinking purpose category. The PCA showed pH, Na+, Ca2+, HCO3- and fluoride with strong loading, which pointed out geogenic source of fluoride contamination. Therefore, it was inferred that the groundwater of the contaminated areas must be treated and made potable before consumption. The outcomes of the present study will be helpful for the regulatory boards and policymaker for defining the actual impact and remediation goal.

Molecular Insights into the Inhibitory Role of α-Crystallin against γD-Crystallin Aggregation.

Cataracts, a major cause of global blindness, contribute significantly to the overall prevalence of blindness. The opacification of the lens, resulting in cataract formation, primarily occurs due to the aggregation of crystallin proteins within the eye lens. Despite the high concentration of these crystallins, they remarkably maintain the lens transparency and refractive index. α-Crystallins (α-crys), acting as chaperones, play a crucial role in preventing crystallin aggregation, although the exact molecular mechanism remains uncertain. In this study, we employed a combination of molecular docking, all-atom molecular dynamics simulations, and advanced free energy calculations to investigate the interaction between γD-crystallin (γD-crys), a major structural protein of the eye lens, and α-crystallin proteins. Our findings demonstrate that α-crys exhibits an enhanced affinity for the NTD2 and CTD4 regions of γD-crys. The NTD2 and CTD4 regions form the interface between the N-terminal domain (NTD) and the C-terminal domain (CTD) of the γD-crys protein. By binding to the interface region between the NTD and CTD of the protein, α-crys effectively inhibits the formation of domain-swapped aggregates and mitigates protein aggregation. Analysis of the Markov state models using molecular dynamics trajectories confirms that minimum free energy conformations correspond to the binding of the α-crystallin domain (ACD) of α-crys to NTD2 and CTD4 that form the interdomain interface.

Structure and energetics guide dynamic behaviour in a T = 3 icosahedral virus capsid.

Although virus capsids appear as rigid, symmetric particles in experimentally determined structures; biochemical studies suggest a significant degree of structural flexibility in the particles. We carried out all-atom simulations on the icosahedral capsid of an insect virus, Flock House Virus, which show intriguing differences in the degree of flexibility of quasi-equivalent capsid subunits consistent with previously described biological behaviour. The flexibility of all the ß and γ subunits of the protein and RNA fragments is analysed and compared. Both γA subunit and RNA fragment exhibit higher flexibility than the γB and γC subunits. The capsid shell is permeable to the bidirectional movement of water molecules, and the movement is heavily influenced by the geometry of the capsid shell along specific symmetry axes. In comparison to the symmetry axes along I5 and I3, the I2 axis exhibits a slightly higher water content. This enriched water environment along I2 could play a pivotal role in facilitating the structural transitions necessary for RNA release, shedding some light on the intricate and dynamic processes underlying the viral life cycle. Our study suggests that the physical characterization of whole virus capsids is the key to identifying biologically relevant transition states in the virus life cycle and understanding the basis of virus infectivity.

Variability of groundwater fluoride and its proportionate risk quantification via Monte Carlo simulation in rural and urban areas of Agra district, India.

This study quantifies the groundwater fluoride contamination and assesses associated health risks in fluoride-prone areas of the city of Taj Mahal, Agra, India. The United States Environmental Protection Agency (USEPA) risk model and Monte Carlo Simulations were employed for the assessment. Result revealed that, among various rural and urban areas Pachgain Kheda exhibited the highest average fluoride concentration (5.20 mg/L), while Bagda showed the lowest (0.33 mg/L). Similarly, K.K. Nagar recorded 4.38 mg/L, and Dayalbagh had 1.35 mg/L. Both urban and rural areas exceeded the WHO-recommended limit of 1.5 mg/L, signifying significant public health implications. Health risk assessment indicated a notably elevated probability of non-carcinogenic risk from oral groundwater fluoride exposure in the rural Baroli Ahir block. Risk simulations highlighted that children faced the highest health risks, followed by teenagers and adults. Further, Monte Carlo simulation addressed uncertainties, emphasizing escalated risks for for children and teenagers. The Hazard Quotient (HQ) values for the 5th and 95th percentile in rural areas ranged from was 0.28-5.58 for children, 0.15-2.58 for teenager, and 0.05-0.58 for adults. In urban areas, from the range was 0.53 to 5.26 for children, 0.27 to 2.41 for teenagers, and 0.1 to 0.53 for adults. Physiological and exposure variations rendered children and teenagers more susceptible. According to the mathematical model, calculations for the non-cancerous risk of drinking water (HQ-ing), the most significant parameters in all the targeted groups of rural areas were concentration (CW) and Ingestion rate (IR). These findings hold relevance for policymakers and regulatory boards in understanding the actual impact and setting pre-remediation goals.

Effect of mutations on the folding and stability of γD-crystallin protein.

Interprotein interactions between the partially unfolded states of γD-crystallin (γD-crys) protein are known to cause cataracts. Therefore, understanding the unfolding pathways of native γD-crys is extremely crucial to delineate their aggregation mechanism. In this study, we have performed extensive all-atom Molecular Dynamics simulations with explicit solvent to understand the role of the critical residues that drive the stability of the motifs and domains of γD-crys in its wild type and mutant forms. Our findings show that while the individual motifs of wild type are not stable in the native form, the individual domains remain structurally stable at 425K. This enhanced stability of the domain was attributed to the hydrophobic interactions between the motifs. Single and double point mutations of the domains with negatively charged aspartic and glutamic acid amino acid residues (I3E, W42D, W42E, I3D/W42D, I3E/W42E, and L92D/W157D) decreases the structural stability, leading to unfolding of individual domains of γD-crys. We believe that our study sheds light on the weakest links of γD-crys, along with the role of interactions stabilizing the domains. Further, this study bolsters and provides a better understanding of the domain swapping mechanism of aggregation of γD-crys.Communicated by Ramaswamy H. Sarma.

Understanding the helical stability of charged peptides.

Cationic helical peptides play a crucial role in applications such as anti-microbial and anticancer activity. The activity of these peptides directly correlates with their helicity. In this study, we have performed extensive all-atom molecular dynamics simulations of 25 Lysine-Leucine co-polypeptide sequences of varying charge density ( λ ) and patterns. Our findings showed that, an increase in the charge density on the peptide leads to a gradual decrease in the helicity up to a critical charge density λ c . Beyond λ c , a complete helix to coil transition was observed. The decrease in the helicity is correlated with the increased number of water molecules in first solvation shell, solvent-exposed surface area, and a higher value of the radius of gyration of the peptide.

Laparoscopic excision of a schwannoma arising in the psoas muscle.

Schwannoma occurring in the psoas muscle is rare. We report a 49-year-old male who presented to the orthopaedic oncosurgery team with persistent lower back pain radiating to the right lower limb following a fall on the back a few months ago. Magnetic resonance imaging revealed a well-defined lesion in the right psoas muscle at the level of third lumbar vertebra (L3). He underwent a laparoscopic excision of this mass using one 10 mm and two 5 mm ports. Intraoperative frozen section after a complete excision showed this to be a benign schwannoma. He was discharged the day after surgery. His symptoms gradually reduced over a period of time and he remains well 3 years after surgery. This case highlights the feasibility and safety of minimally invasive treatment of this rare tumour.

Immunogenicity and safety of two quadrivalent influenza vaccines in healthy adult and elderly participants in India - A phase III, active-controlled, randomized clinical study.

BACKGROUND: This study was conducted to compare the immunogenicity and safety profile of two quadrivalent influenza vaccines (QIVs) in healthy adults (18-60 years) and elderly (>61 years) participants. METHOD: This phase III study was conducted from March 2018 to April 2018 across 12 sites in India. In this randomized, observer-blind, active-controlled study, 480 participants were randomized to receive a single dose of test vaccine (subunit, inactivated influenza vaccine; Influvac® Tetra, Abbott) (n = 240) or reference vaccine (split virion, inactivated influenza vaccine; VaxiFlu-4, Zydus Cadilla Healthcare) (n = 240). The primary objective was to describe and compare the immunogenicity of each vaccination group based on hemagglutination inhibition (HI) assay seroprotection and seroconversion rates, and geometric mean fold increase (GMFI) against four vaccine strains in two age groups. Safety and reactogenicity were also compared for the vaccines in both the age groups. RESULTS: The pre- and post-vaccination HI titers for both the vaccines were comparable. The GMFI varied from 4.3 - 22.7 in the test and 3.7-21.6 in the reference vaccine group. The seroprotection rates were >90% for the A-strains and ranged between >43% and <60% for B-strains for both the vaccines. Seroconversion rates varied between 41.4% and 78.8%. Overall, the reported adverse events (AEs) for both the vaccines were <1% and comparable. Reported local and systemic reactions were comparable. CONCLUSION: Influvac® Tetra elicited an adequate immune response with a favorable safety profile which was comparable with the reference vaccine. (Clinical trial registry number: CTRI/2018/02/012222).

Can 18F-FDG PET/CT alone or combined with radiology be used to reliably grade cartilage bone neoplasms for surgical decision making?

OBJECTIVE: Treatment of chondrosarcomas is grade based; intralesional curettage for grade 1 and resection for grade 2 or more. Currently used methods to determine grades before surgery are not highly accurate and create a dilemma for the surgeon. We have used a PET-CT combined with imaging to answer the following study questions: (1) Does SUVmax value from an 18F-FDG PET/CT correlate with the grade of chondrosarcoma? (2) Can a cutoff SUVmax value be used to differentiate between various grades of chondroid neoplasms with sufficient sensitivity and specificity? (3) Does SUVmax guide the clinician and add value to radiology in offering histologic grade-dependent management? METHODS: SUVmax values of patients with suspected chondrosarcoma were retrospectively correlated with the final histology grade for the operated patients. Radiologic parameters and radiology aggressiveness scores (RAS) were reevaluated and tabulated. RESULTS: Totally 104 patients with chondroid tumors underwent 18F-FDG PET/CT assessment. In total 73 had tissue diagnosis available as a pretreatment investigation. Spearman correlation indicated that there was a significant positive association between SUVmax and the final histology grading of chondroid tumors (correlation coefficient = 0.743; P < 0.01). SUVmax cutoff of 13.3 was 88.9% sensitive and 100% specific for diagnosing dedifferentiated chondrosarcomas. An RAS cutoff value of 3 or more could diagnose IHGCS with a sensitivity of 80.7% and specificity of 93.75%. Adding an SUVmax cutoff of 3.6 improves the sensitivity to 89.5%. CONCLUSION: SUVmax value can reliably help diagnose dedifferentiated chondrosarcoma and when added to the radiology score can improve the accuracy of grading chondrosarcoma.

Extended Curettage for Giant Cell Tumors of Bone: A Surgeon's View.

The key to intralesional surgical treatment of giant cell tumor of bone (GCTB) is extended curettage. As GCTB is locally aggressive with a high propensity for local recurrence, a primary factor of surgical treatment is the ability to achieve local tumor clearance. GCTB commonly affects the epimetaphyseal region of the bone, which may compromise the integrity of the articular surface. With the exception of expendable bone that may be considered for resection without the challenge of reconstruction (e.g., the proximal aspect of the fibula or the distal aspect of the ulna), a large majority of cases of GCTB can be treated with joint-preserving techniques. In the present article, we share a video demonstration including the surgeon view of intralesional surgery for GCTB, with emphasis on the 360° visualization of the tumor cavity, dilemmas regarding use of adjuvants for extended curettage, and options in cavity reconstruction. DESCRIPTION: The surgical procedure involves 4 essential components.(1) Surgical exposure and isolation of the soft tissues. The technique begins with a complete exposure that allows visualization of the entire tumor cavity. The initial part of the exposure involves getting to the bone and to the soft-tissue mass outside the bone, when present. The muscles are separated from the bone and retracted away from the soft-tissue component of the tumor. Soft tissue is adequately retracted to allow complete visualization of the tumor cavity. The tissues around the cavity are protected by placing hydrogen peroxide-soaked mops around the tumor cavity. The aim is to isolate the bone opening and avoid any contamination of soft tissue by the tumor, as hydrogen peroxide kills GCTB cells on contact1. The soft-tissue mass of the tumor is removed en bloc with a cover of normal tissue in order to prevent spillage into uninvolved tissues. Ward and Li advise the use of cautery for this part of the exposure in order to minimize contamination because high-temperature cautery kills the tumor2. The initial opening into the osseous tumor cavity is made smaller in order to control the tumor spillage, and then enlarged in order to gain complete visualization.(2) Curetting and burring for tumor clearance. The walls are curetted, using the sharp edges of the curet. Good visualization is the key to meticulous and complete curetting. We recommend the use of a surgical loupe and headlight for adequate visualization1. Tumor cavities often have overhanging osseous ridges with tumor hidden behind them. A curet may not be useful for breaking these hard osseous ridges; a burr is best utilized for this task. In addition to breaking the ridges, a high-speed burr helps to extend the curettage for a few millimeters beyond the grossly visible tumor margin3,4.(3) Use of adjuvants to achieve extended curettage. Various physical and chemical agents have been utilized to control the microscopic disease remaining in the walls following a thorough curettage. Liquid nitrogen, phenol, hydrogen peroxide, alcohol, electrocautery, bone cement, and argon plasma cautery have been utilized as adjuvants. Balke et al. showed that the rate of recurrence decreases with use of more adjuvants, with high-speed burring having the greatest effect on the rate of recurrence, likely as a result of the larger resection and the thermal effect of the burring5. We suggest a case-by-case use of specific adjuvants, but in our experience, a high-speed burr is always utilized, hydrogen peroxide is utilized commonly when safe, and argon-plasma cautery is utilized judiciously.(4) Reconstruction of the cavity. The defect may be filled with bone, cement, or a combination of both. We suggest an individual, case-by-case approach to the reconstruction. In cases in which >25% of the articular surface is undermined2, subchondral bone grafting is recommended prior to cementing (i.e., a sandwich procedure). ALTERNATIVES: GCTB requires tumor clearance for local control. One alternative to intralesional surgical treatment performed around the knee is resection of the tumor-affected segment of bone and reconstruction with an endoprosthesis. This is a joint-sacrificing alternative and, in our experience, should be reserved for patients with joint involvement, multiply recurrent disease, or insufficient remaining wall to curet. RATIONALE: When adequate tumor clearance is possible, joint-salvaging intralesional surgical treatment remains the superior option to achieve physiological joint function6. Indications for this procedure include maintained or restorable joint congruity and construct stability allowing early mobilization. EXPECTED OUTCOMES: The rate of local recurrence following intralesional surgical treatment ranges from 16% to 25%1,7. The use of a high-speed burr is an essential part of the curettage5, and hydrogen peroxide is a safe choice for an adjuvant, if desired and when suitable, to provide greater local control8. Reconstruction with bone, cement, or both is acceptable, but we recommend building up a few millimeters of subchondral bone with bone graft before cement filling1,9. IMPORTANT TIPS: Illumination and magnification within the tumor cavity provide better visualization.Isolation of the soft tissue around the tumor with use of hydrogen peroxide-soaked mops can prevent seeding and contamination.Meticulous tumor clearance is more important to minimize recurrence than the use of adjuvants.Use of a C-arm helps to better guide extension of the curettage and avoid inadvertent joint penetration.Maintaining joint congruity is essential.

Looking through glass: Knowledge discovery from materials science literature using natural language processing.

Most of the knowledge in materials science literature is in the form of unstructured data such as text and images. Here, we present a framework employing natural language processing, which automates text and image comprehension and precision knowledge extraction from inorganic glasses' literature. The abstracts are automatically categorized using latent Dirichlet allocation (LDA) to classify and search semantically linked publications. Similarly, a comprehensive summary of images and plots is presented using the caption cluster plot (CCP), providing direct access to images buried in the papers. Finally, we combine the LDA and CCP with chemical elements to present an elemental map, a topical and image-wise distribution of elements occurring in the literature. Overall, the framework presented here can be a generic and powerful tool to extract and disseminate material-specific information on composition-structure-processing-property dataspaces, allowing insights into fundamental problems relevant to the materials science community and accelerated materials discovery.

Comparative Efficacy of Transsphenoidal Endonasal Endoscopic and Microscopic Pituitary Surgery at Single Center of a Developing Country.

Objective This study was aimed to compare comparative efficacy of transsphenoidal endonasal endoscopic and microscopic pituitary surgery at single center of a developing country. Methods This study included 198 patients in which 50 patients were studied prospectively and 148 patients were studied retrospectively, diagnosed with pituitary adenoma who presented to neurosurgery department at Sawai Man Singh hospital in Jaipur, India, and were operated via transsphenoidal route between 2013 and 2018. Patients' records were reviewed and relevant clinical and surgical data were collected. Patients were divided into two groups based on the surgical procedure performed, endoscopic endonasal transsphenoid approach (group 1) and microscopic transsphenoidal approach (group 2). Outcomes, in terms of efficacy and the resulting complications of each procedure were compared and analyzed. Results A total of 198 patients with pituitary adenoma were operated during the study period. Among them, 119 (60.1%) patients were operated by endoscopic and 79 (39.9%) patients were operated by microscopic transsphenoidal approach. In endoscopic group, intraoperative cerebrospinal fluid (CSF) leak was present in 39 patients (32.77%) and 23 (29.11%) in microscopic group. Complete tumor removal was achieved in 69.75% in endoscopic and 48.13% in microscopic group ( p = 0.004). Endocrine control was achieved in 78.94% (30 out of 38) in endoscopic and 68.18% (15 out of 22 patients) in microscopic group. Conclusion The transsphenoidal approaches for resection of pituitary adenoma, both endoscopic and microscopic approach, are minimally invasive and effective for disease control. Both the approaches lead to similar endocrine control, visual symptoms, complications, and long-term outcome. Therefore, the selection of the final approach should be individualized, ultimately depending on the surgeons' comfort, experience, and familiarity with the particular technique.

Reconstructive Challenges of Distal Tibia Bone Tumors: Extracorporeally Irradiated Autograft Combined with a Nonvascularized Autograft Fibula for Superior Reconstruction and Functional Outcomes When Compared to Ipsilateral Pedicled Fibula Transfer Alone.

INTRODUCTION: Traditionally, centralization of the fibula with fusion across the tibiotalar joint has been used to reconstruct distal tibial defects. Although effective, it requires long periods of protected weight-bearing. The fibula or the fixation often fails before fibular hypertrophy necessitating multiple additional surgeries. A method of using ECRT with the available ipsilateral fibula (nonvascularized) to reconstruct the distal tibia defect with the aim of early return to weight-bearing was evolved. This paper documents our early experience. Patients and Methods. Four patients; with the diagnosis of osteosarcoma in 3 patients and recurrent giant cell tumor of the bone in 1 patient, underwent resection of the distal tibia for tumors between 2017 and 2019. Extracorporeally irradiated (50 Gy) distal tibia along with ipsilateral nonvascularized fibula was used to bridge the defect and fuse the tibiotalar joint. A plate was used to rigidly hold the construct. The final outcome was compared to the historical control group that underwent only pedicled ipsilateral fibula transposition and ankle arthrodesis without recycled autograft or allograft between 2009 and 2017. Oncological reconstruction and functional outcomes were compared for each group. Patient reported outcomes on the acceptability of ankle fusion; cosmesis and function were analyzed and compared between the two groups. RESULTS: The mean resection length in the study group (4 patients) was 7.75 cm (7 to 8.5 cm). As compared to the historical cohort of 7 patients, the study population showed statistically superior results in all reconstruction, functional, and patient-reported outcomes except time to proximal junction union (p=0.068). There were no reconstruction failures, infection, or nonunions in the study group, whereas the control comparative group had 2 proximal junction nonunions and a mean time to fibular hypertrophy of 143 weeks (82 to 430 weeks) with fibula centralization. Earlier weight-bearing was allowed (mean 26.75 weeks; median 27 weeks) compared to (mean 80.75 weeks; median 80 weeks) in the control group. CONCLUSION: We think that ECRT with ipsilateral vascularized fibula is a promising method of reconstructing the distal tibia. The recycled autograft tibia added strength to the distal tibia construct in our study and aided the anatomical reconstruction of the distal tibia. The patient-reported outcomes for cosmesis and acceptability add to the benefits of performing this procedure. Consistent early union across the proximal junction and earlier weight-bearing were clear advantages of this method.

Do irradiated osteo-articular recycled tumor autografts still hold promise for biological joint reconstruction? Our experience with acetabular and proximal ulna ECRT.

BACKGROUND: Joint reconstruction following resection of malignant bone tumors is challenging in itself in spite of several options in hand. Ability to restore joint anatomy, function and mobility while achieving optimal oncological outcomes are the requirement of reconstructions today. While biological reconstructions (allograft or recycled tumor autografts) following tumor bone surgery are popular for intercalary resections not involving the joint, their use for osteo-articular reconstructions are associated with concerns over cartilage and joint health. We have used extracorporeal radiation therapy (ECRT) and re-implantation of the osteoarticular segment as a size matched recycled tumor autograft reconstruction after complex acetabular and proximal ulnar resections; owing to the lack of significantly superior reconstruction alternatives in these locations and also review the current literature on other biological/non-biological reconstruction options. QUESTIONS/PURPOSES: (1) What are the oncological, reconstruction and functional outcomes with osteo-articular reconstruction using ECRT and re-implantation of recycled tumor autograft for the acetabulum and olecranon? (2) Is there an evidence of cartilage loss, joint damage or avascular necrosis resulting from irradiation of the articular autograft? METHODS: 19 patients with primary bone tumors underwent limb salvage surgery with en-bloc resection and reconstruction using the resected articular tumor bone after treating it with extra-corporeal irradiation of 50-60Gy. These included 16 acetabular and 3 proximal ulnar. While all patients were included for oncological assessment; minimum follow-up of 24 months was considered for final outcome assessment of function and joint status. RESULTS: MSTS scores of the 16 acetabular reconstruction patients with minimum 2 years follow-up was 87% (26/30). Neither delayed union, non-union at osteotomy sites nor was any fractures reported in the irradiated graft. There was no local recurrence within the irradiated graft and only 1 patient required graft excision for uncontrolled infection. All 3 patients of proximal ulna reconstruction achieved healing and full range of movement of the elbow. Scores of MSTS: 100% (30/30), MEPS: 100 and DASH: zero was achieved. Two patients developed osteonecrosis of the femoral head; one requiring a joint replacement and one awaiting replacement. One patient of acetabular reconstruction has joint space narrowing on radiographs with mild clinical symptoms. CONCLUSIONS: Extracorporeal radiotherapy and re-implantation after osteo-articular resection is an oncologically safe option offering promising outcome in our small series. The availability of size-matched graft, thus avoiding inherent problems of allograft also provides a better economic option over endoprosthesis and its associated complications in select sites. The results can deteriorate over time that may require secondary reconstructive procedures like joint replacement. LEVEL OF EVIDENCE: Level IV, Therapeutic Study.

Evaluation of the Efficacy and Safety of Azilsartan in Adult Patients with Essential Hypertension: A Randomized, Phase-III Clinical Study in India.

BACKGROUND: Globally, women and men over the age of 25 years suffer from hypertension, the need for new treatment strategies to treat hypertension is due to the multi-faceted nature of the disease. Lack of optimal blood pressure control can lead to multiple complications. Therefore, this phase 3 study was conducted to assess the efficacy, safety and tolerability of potential product azilsartan hydrochloride for reduction in blood pressure in Indian patients with essential hypertension. METHODS: This was a prospective, multicentre, randomized, comparative, parallel study of 303 participants over six weeks of treatment period with either azilsartan 40 mg or azilsartan 80 mg or telmisartan 40 mg in adult patients with essential hypertension. The primary endpoint was the change in mean trough sitting clinic systolic blood pressure (scSBP) from baseline to week 6. The secondary endpoints were the change in mean trough sitting clinic diastolic blood pressure (scDBP) from baseline and change in the 24-hour mean ambulatory systolic blood pressure (SBP)and diastolic blood pressure (DBP) from baseline. RESULTS: The change in mean trough scSBP from baseline to week 6 was -27.2 ± 9.99, -28.2 ± 10.06 and -26.7 ± 9.72 (Per Patient (PP) Population) and -27.2 ± 9.93, -28.3 ± 10.01 and -26.7 ± 9.67 (Intent to Treat (ITT) Population) in the azilsartan 40mg, 80mg and telmisartan 40mg groups respectively. The lower limit of 95% CI of difference in change in mean systolic blood pressure was -2.35(Azilsartan 40mg) and 1.32 (Azilsartan 80mg) is less than the non-inferiority margin (i.e. 2.67). The change in mean trough scDBP from baseline to week 6 was -13.1 ± 8.46, -12.9 ± 7.20, and -13.0 ± 7.96 (PP) and -13.1 ± 8.42, -12.9 ± 7.16 and -13.0 ± 7.92 (ITT) in Azilsartna 40 mg, Azilsartan 80 mg and Telmisartan 40 mg respectively. The reduction in trough scDBP in Azilsartan 40 mg (p=0.9461: PP; p=0.9330: ITT) and Azilsartan 80 mg (p=0.9090: PP; p=0.9158: ITT) was not statistically significant compared to Telmisartan 40 mg. The difference in fall in the trough scSBP, scDBP and ambulatory SBP and DBP was similar between the groups from baseline to week 6 (P >0.05). Headache and dizziness were the most frequent treatmentrelated treatment-emergent adverse events. CONCLUSION: Azilsartan is an effective blood pressure lowering drug and well tolerated and was non- inferior to telmisartan in its safety and efficacy.

Does a Modified Technique to Achieve Arthrodesis of the Wrist After Resection of the Distal Radius and Translocating the Ipsilateral Ulna as a Vascularized Graft to Reconstruct the Defect Improve Grip Strength and Outcomes Scores?

BACKGROUND: Ten years ago, we reported the results of a procedure in which we translocated the ipsilateral ulna as a vascularized autograft to reconstruct defects of the distal radius after tumor resection, with excellent functional results. At that time, wrist arthrodesis was achieved by aligning the translocated ulna with the scapholunate area of the carpus and usually the third metacarpal. This resulted in wrist narrowing. We then wondered if aligning the translocated ulna with the scaphoid and the second metacarpal would result in ulnar deviation and thereby improve grip strength. We believed lateralization would reduce the wrist narrowing that occurs with fusion to the third metacarpal and would make the cosmesis more acceptable. We also modified the incision to dororadial to make the scar less visible and thus improve the cosmesis. QUESTIONS/PURPOSES: (1) Is there an objective improvement in grip strength and functional scores (Musculoskeletal Tumor Society [MSTS] and Mayo wrist) when the translocated ulna is lateralized and the wrist is fused with the translocated ulna and aligned with the second metacarpal versus when the translocated ulna is aligned with the third metacarpal? (2) Did lateralization caused by the wrist fusion aligned with the second metacarpal minimize wrist narrowing as measured by the circumference compared with the fusion aligned with the third metacarpal? METHODS: From 2010 and 2018, we treated 40 patients with distal radius tumors at our institution, 30 of whom had a distal radius enbloc resection. Twenty-eight patients had an ipsilateral ulna translocation and wrist arthrodesis in which the radius and translocated ulna were aligned with either the second (n = 15) or the third (n = 13) metacarpals. Two patients in the second metacarpal group and three patients in the third metacarpal group were lost to follow-up before 24 months after surgery and were excluded. A retrospective analysis of 23 patients (20 with giant cell tumors and three with malignant bone tumors) included a review of radiographs and institutional tumor database for surgical and follow-up records to study oncologic (local disease recurrence), reconstruction (union of osteotomy junctions, implant breakage or graft fracture, and wrist circumference), and functional outcomes (MSTS and Mayo wrist scores and objective grip strength assessment compared with the contralateral side). The results were compared for each study group (second metacarpal versus third metacarpal). There was no difference in the incidence of local recurrence or the time to union between the two groups. There were no implant breakages or graft fractures noted in either group. RESULTS: Patients in the second metacarpal group lost less grip strength compared with the unoperated side in the third metacarpal group (median 12% [range -30% to 35%] versus median 28% [15% to 42%], difference of medians 16%; p = 0.006). There were no between-group differences in terms of MSTS (median 30 [24 to 30] versus median 26.5 [22 to 30], difference of medians 3.5; p = 0.21) or Mayo wrist scores (median 83 [65 to 100] versus median 72 [50 to 90], difference of medians 11; p = 0.10). The second metacarpal group also had less wrist narrowing as seen from the median difference in circumference between the operated and unoperated wrists (median narrowing 10 mm [3 to 35 mm] in the second metacarpal group versus median 30 mm [15 to 35 mm] in the third metacarpal group, difference of medians 20 mm; p = 0.04). CONCLUSION: Wrist arthrodesis after ulna translocation with alignment of the translocated ulna and the second metacarpal provides a functional position with ulnar deviation that offers some improvement in grip strength but no improvement in the MSTS or Mayo scores. Radialization/lateralization of the translocated ulna achieved from the alignment with the second metacarpal decreases the reduction in the wrist circumference and therefore reduces wrist narrowing. LEVEL OF EVIDENCE: Level III, therapeutic study.