Fifty Years of Cervical Myelopathy Research: Results from a Bibliometric Analysis

We performed bibliometric analysis of the research papers published on clinical cervical spondylotic myelopathy (CSM) in the last 50 years. We extracted bibliometric data from Scopus and PubMed from 1970 to 2020 pertaining to clinical studies of CSM. The predominant journals, top cited articles, authors, and countries were identified using performance analysis. Science mapping was also performed to reveal the emerging trends, and conceptual and social structures of the authors and countries. Bibliometrix R-package was deployed for the study. The total numbers of clinical studies available in PubMed and Scopus were 1,302 and 3,470, respectively. The most cited article was published by Hilibrand AS, as observed in Scopus. Regarding the conceptual structure of the research, two main research themes were identified, one involving symptomatology, scientific-scale-based objective evaluation of symptoms, and surgical removal of the offending culprit, while the other was based on patho-etiology, relevant diagnostic modalities, and the surgery commonly performed for CSM. In terms of emerging trends, in recent times there is an increasing trend of scale-based objective evaluations, along with investigations of advanced nonoperative management. The United States is the most productive country, whereas Canada tops the list for inter-country collaboration. The trend of research showed a shift toward noninvasive procedures.

The Dual-Antigen Ad5 COVID-19 Vaccine Delivered as an Intranasal Plus Subcutaneous Prime Elicits Th1 Dominant T-Cell and Humoral Responses in CD-1 Mice

In response to the need for an efficacious, thermally-stable COVID-19 vaccine that can elicit both humoral and cell-mediated T-cell responses, we have developed a dual-antigen human adenovirus serotype 5 (hAd5) COVID-19 vaccine in formulations suitable for subcutaneous (SC), intranasal (IN), or oral delivery. The vaccine expresses both the SARS-CoV-2 spike (S) and nucleocapsid (N) proteins using an hAd5 platform with E1, E2b, and E3 sequences deleted (hAd5[E1-, E2b-, E3-]) that is effective even in the presence of hAd5 immunity. In the vaccine, S is modified (S-Fusion) for enhanced cell-surface display to elicit humoral responses and N is modified with an Enhanced T-cell Stimulation Domain (N-ETSD) to direct N to the endosomal/lysosomal pathway to increase MHC I and II presentation. Initial studies using subcutaneous (SC) prime and SC boost vaccination of CD-1 mice demonstrated that the hAd5 S-Fusion + N-ETSD vaccine elicits T-helper cell 1 (Th1) dominant T-cell and humoral responses to both S and N. We then compared SC to IN prime vaccination with either an SC or IN boost post-SC prime and an IN boost after IN prime. These studies reveal that IN prime/IN boost is as effective at generating Th1 dominant humoral responses to both S and N as the other combinations, but that the SC prime with either an IN or SC boost elicits greater T cell responses. In a third study to assess the power of the two routes of delivery when used together, we used a combined SC plus IN prime with or without a boost and found the combined prime alone to be as effective as the combined prime with either an SC or IN boost in generating both humoral and T-cell responses. The findings here in CD-1 mice demonstrate that combined SC and IN prime-only delivery has the potential to provide broad immunity - including mucosal immunity - against SARS-CoV-2 and supports further testing of this delivery approach in additional animal models and clinical trials.

A recombinant ACE2 Triple Decoy that traps and neutralizes SARS-CoV-2 shows enhanced affinity for highly transmissible SARS-CoV-2 variants

The highly-transmissible SARS-CoV-2 variants now replacing the first wave strain pose an increased threat to human health by their ability, in some instances, to escape existing humoral protection conferred by previous infection, neutralizing antibodies, and possibly vaccination. Thus, other therapeutic options are necessary. One such therapeutic option that leverages SARS-CoV-2 initiation of infection by binding of its spike receptor binding domain (S RBD) to surface-expressed host cell angiotensin-converting enzyme 2 (ACE2) is an ACE2 decoy that would trap the virus by competitive binding and thus inhibit propagation of infection. Here, we used Molecular Dynamic (MD) simulations to predict ACE2 mutations that might increase its affinity for S RBD and screened these candidates for binding affinity in vitro. A double mutant ACE2(T27Y/H34A)-IgG1FC fusion protein was found to have very high affinity for S RBD and to show greater neutralization of SARS-CoV-2 in a live virus assay as compared to wild type ACE2. We further modified the double mutant ACE2 decoy by addition of an H374N mutation to inhibit ACE2 enzymatic activity while maintaining high S RBD affinity. We then confirmed the potential efficacy of our ACE2(T27Y/H34A/H374N)-IgG1FC Triple Decoy against S RBD expressing variant-associated E484K, K417N, N501Y, and L452R mutations and found that our ACE2 Triple Decoy not only maintains its high affinity for S RBD expressing these mutations, but shows enhanced affinity for S RBD expressing the N501Y or L452R mutations and the highest affinity for S RBD expressing both the E484K and N501Y mutations. The ACE2 Triple Decoy also demonstrates the ability to compete with wild type ACE2 in the cPass surrogate virus neutralization in the presence of S RBD with these mutations. Additional MD simulation of ACE2 WT and decoy interactions with S RBD WT or B.1.351 variant sequence S RBD provides insight into the enhanced affinity of the ACE2 decoy for S RBD and reveals its potential as a tool to predict affinity and inform therapeutic design. The ACE2 Triple Decoy is now undergoing continued assessment, including expression by a human adenovirus serotype 5 (hAd5) construct to facilitate delivery in vivo. Summary sentenceAn ACE2(N27Y/H34A/H374N)-IgG1FC fusion protein decoy sustains high affinity to all SARS-CoV-2 spike receptor binding domain (RBD) protein variants tested, shows enhanced affinity for the N501Y and L452R variants, and the highest affinity for combined N501Y and E484K variants.

A Next Generation Bivalent Human Ad5 COVID-19 Vaccine Delivering Both Spike and Nucleocapsid Antigens Elicits Th1 Dominant CD4+, CD8+ T-cell and Neutralizing Antibody Responses

In response to the health crisis presented by the COVID-19 pandemic, rapid development of safe and effective vaccines that elicit durable immune responses is imperative. Recent reports have raised the concern that antibodies in COVID-19 convalescent patients may not be long lasting and thus even these individuals may require vaccination. Vaccine candidates currently in clinical testing have focused on the SARS-CoV-2 wild type spike (S) protein (S-WT) as the major antigen of choice and while pre-clinical and early clinical testing have shown that S elicits an antibody response, we believe the optimal vaccine candidate should be capable of inducing robust, durable T-cell responses as well as humoral responses. We report here on a next generation bivalent human adenovirus serotype 5 (hAd5) vaccine capable of inducing immunity in patients with pre-existing adenovirus immunity, comprising both an S sequence optimized for cell surface expression (S-Fusion) and a conserved nucleocapsid (N) antigen designed to be transported to the endosomal subcellular compartment, with the potential to generate durable immune protection. Our studies suggest that this bivalent vaccine is optimized for immunogenicity as evidenced by the following findings: (i) The optimized S-Fusion displayed improved S receptor binding domain (RBD) cell surface expression compared to S-WT where little surface expression was detected; (ii) the expressed RBD from S-Fusion retained conformational integrity and recognition by ACE2-Fc; (iii) the viral N protein modified with an enhanced T-cell stimulation domain (ETSD) localized to endosomal/lysosomal subcellular compartments for MHC I/II presentation; and (iv) these optimizations to S and N (S-Fusion and N-ETSD) generated enhanced de novo antigen-specific B cell and CD4+ and CD8+ T-cell responses in antigen-naive pre-clinical models. Both the T-cell and antibody immune responses to S and N demonstrated a T-helper 1 (Th1) bias. The antibody responses were neutralizing as demonstrated by two independent SARS-CoV-2 neutralization assays. Based on these findings, we are advancing this next generation bivalent hAd5 S-Fusion + N-ETSD vaccine as our lead clinical candidate to test for its ability to provide robust, durable cell-mediated and humoral immunity against SARS-CoV-2 infection. Further studies are ongoing to explore utilizing this vaccine construct in oral, intranasal, and sublingual formulations to induce mucosal immunity in addition to cell-mediated and humoral immunity. The ultimate goal of an ideal COVID-19 vaccine is to generate long-term T and B cell memory.

Bioaersols in orthopedic surgical procedures and implications for clinical practice in the times of COVID-19 pandemic: a protocol for systematic review and meta-analysis

BackgroundOrthopedic surgical procedures involve a number of aerosol generating procedures; these include electrocautery, power instruments for bone cutting, burring and drilling, and tools for wound lavage. This assumes a great significance in the context of the current COVD-19 pandemic, as there are chances of aerosol-borne disease transmission in orthopedic surgical procedures. Hence, this systematic review and meta-analysis will be undertaken to assimilate and analyse the available evidence on bioaerosols in orthopedic surgical procedures and their significance with respect to SARS-CoV-2 virus transmission. ObjectivesTo determine the characteristics (amount and/or density, size, infectivity, and spread etc.) of bioaerosols found in orthopaedic operating rooms (ORs) and to determine the characteristics of aerosols generated by different orthopaedic power tools and devices. MethodsA systematic review and meta-analysis will be conducted. The PRISMA guidelines will be strictly followed. The primary search will be conducted on the PubMed, EMBASE, Scopus, Cochrane Library, medRxiv, bioRxix and Lancet preprint databases, using a well-defined search strategy. Any original research study (including cohort, case-control, case series, cadaveric studies and studies, animal models, laboratory based experimental studies) looking at aerosol generation in orthopedic surgical procedures, or aerosol generation by orthopaedic power tools and devices will included. Outcome measures will include characteristics (amount and/or density, size, infectivity, and spread etc.) of bioaerosols found in orthopaedic operating rooms (ORs) and those generated by various orthopaedics power tools and devices. Metanalysis using the random-effects model will be conducted to determined pooled estimates of the outcome variables. Heterogeneity will be assessed by the I2 test. Risk of bias will be assessed by the Risk of Bias in Studies estimating Prevalence of Exposure to Occupational risk factors (RoB-SPEO) tool. The overall strength of evidence will be assessed by the GRADE approach.

Epidemiology of pelvic fractures in adults: Our experience at a tertiary hospital / 中华创伤杂志(英文版)

PURPOSE@#Pelvic fractures are severe injuries and are often associated with multiple system injuries, exacerbating the overall outcome. In India, the incidence of pelvic fractures is on a rise due to suboptimal roads and traffics but related literature regarding the overall epidemiology of these injuries is scarce and scanty. Our aim was to study the epidemiology of patients admitted with pelvic fractures at a level 1 trauma centre in India.@*METHODS@#A 16-month (between September 2015 and December 2016) prospective observational study was carried out on trauma patients with pelvic fractures at a level 1 trauma centre of a tertiary care hospital. Demography of patients, mechanism of injuries and complications were recorded prospectively.@*RESULTS@#We observed 75 patients who presented with pelvic fractures, where 56 were males and 19 were females. Mean age of the study population was 37.57 years. Road traffic accidents were the most common mode of injuries. Lateral compression injuries were the most common pattern. Associated injuries frequently encountered were lower extremities and acetabulum fractures, blunt abdominal trauma, urogenital injuries and head injuries. Out of the 75 patients, 52 were treated surgically and 23 were managed by conservative methods. Associated injuries of the extremities, head, abdomen and urogenital system indicated a longer hospital stay.@*CONCLUSION@#Pelvic fractures, although belong to a relatively rare trauma subset, cause a high morbidity and mortality with considerable burden on the economy. Proper road safety training and driving etiquettes along with its strict implementation in true sense and spirit are the need of the hour.

Clear cell chondrosarcoma calcaneum - a case report and review of literature.

Chondrosarcoma is the second most common primary bone malignancy accounting for 20-25% of all bone sarcomas. However chondrosarcoma of the foot is rare with just a handful of cases being described. Among the subtypes clear cell variant is the rarest and has never been documented in the foot. We present a rare case of clear cell chondrosarcoma of the calcaneum with multiple metastases that was treated at our institute. The patient was a 62-year old male who presented to us with pain and mass in the left hindfoot with difficulty in walking for 2 years and a discharging ulcer over the lateral aspect for 4 months. Radiography showed aggressive, destructive, lytic lesion in the calcaneum with cortical breach and soft tissue invasion. Bone scan and PET-CT revealed multiple bony metastases and lung metastasis. After initial biopsy, patient underwent below knee amputation and has been in remission since the last 18 months. Given the rarity of this tumor in the calcaneum, this report highlights the importance to consider the possibility of this tumor in the calcaneum as an early diagnosis; complete metastatic workup and expeditious management can thus significantly improve prognosis.

Pediatric Femoral Neck Fractures: Our 10 Years of Experience

BACKGROUND: Femoral neck fractures are rare injuries in children, but the high incidence of long term complications make it an important clinical entity. The aim of this retrospective study was to analyze the clinical outcomes of pediatric femur neck fractures that we managed over a 10 year period. METHODS: The study included 36 children (20 boys and 16 girls) who sustained femoral neck fractures and completed a minimum follow-up of one year. The children were treated either conservatively, or by open reduction and internal fixation (ORIF), or closed reduction and internal fixation (CRIF). The outcomes were analyzed using Ratliff criteria and a detailed record of complications was kept for all patients. RESULTS: The mean age of included patients was 10 years (range, 3 to 16 years) and the average follow-up was 3.2 years (range, 1.1 to 8.5 years). Based on Delbet's classification system, there were 0 type I (transepiphyseal), 16 type II, 11 type III, and 9 type IV fractures. There were 8 undisplaced fractures, 4 of which later displaced after being managed initially in a hip spica. A satisfactory outcome was obtained in 27 (75%) children. Avascular necrosis (AVN) was the most common complication. It was seen in 7 of our patients, all of whom had an unsatisfactory outcome. Other complications included three cases each of coxa vara, non-union, and arthritic changes; and one case each of infection, primary screw perforation of head, and premature epiphyseal closure. Complications were lowest in the group treated by ORIF. Only 2 patients managed exclusively by conservative treatment ultimately achieved a satisfactory outcome. CONCLUSIONS: We believe that internal fixation of pediatric femoral neck fractures is preferred whenever feasible because conservative treatment carries a high risk of failure of reduction. Aggressive operative treatments aimed at anatomical reduction should be the goal and there should be no hesitation in choosing ORIF over CRIF. Outcome of patients is influenced primarily by development of AVN which occurs as an independent entity without much relation to the mode of treatment carried out.

Double segmental tibial fractures--an unusual fracture pattern / 中华创伤杂志(英文版)

A case of a 50-year-old pedestrian who was hit by a bike and suffered fractures of both bones of his right leg was presented. Complete clinical and radiographic assessment showed double segmental fractures of the tibia and multisegmental fractures of the fibula. Review of the literature revealed that this fracture pattern was unique and only a single case was reported so far. Moreover, we discussed the possible mechanisms which can lead to such an injury. We also discussed the management of segmental tibial fracture and the difficulties encountered with them. This case was managed by modern osteosynthesis technique with a pleasing outcome.