Prospective assessment of humoral and cellular immune responses to a 3rd COVID-19 mRNA vaccine dose among immunocompromised individuals.

BACKGROUND: Improved COVID-19 prevention is needed for immunocompromised individuals. METHODS: Prospective study of healthcare workers (HCW) and immunocompromised participants with baseline serology following 2 mRNA vaccines and who were retested after dose 3 (D3); multivariable regression was used to identify predictors of serological responses. IFNγ/TNFα T-cell responses were assessed in a subset. RESULTS: 536 participants were included: 492 immunocompromised [(206 solid organ transplant (SOT), 128 autoimmune, 80 hematologic malignancy (HM), 48 solid tumor, 25 HIV], 44 HCW. D3 significantly increased Spike IgG levels among all, but SOT and HM participants had the lowest median antibody levels post-D3 (increase from 0.09 to 0.83 and 0.27 to 1.92, respectively), versus HCW and persons with HIV, autoimmune conditions, and solid tumors (increases from 4.44 to 19.79, 2.9 to 15.75, 3.82 to 16.32, and 4.1 to 25.54, respectively). Seropositivity post-D3 was lowest for SOT (49.0%) and HM (57.8%), versus others (>90% seropositive). Neutralization post-D3 was lowest among SOT and HM. Predictors of lower antibody levels included low baseline levels and shorter intervals between vaccines. T-cell responses against Spike increased significantly among HCW and non-significantly among immunocompromised individuals. CONCLUSIONS: D3 significantly improves serological but not T-cell responses among immunocompromised individuals. SOT and HM patients have suboptimal responses to D3.

Prospective Evaluation of Coronavirus Disease 2019 (COVID-19) Vaccine Responses Across a Broad Spectrum of Immunocompromising Conditions: the COVID-19 Vaccination in the Immunocompromised Study (COVICS).

BACKGROUND: We studied humoral responses after coronavirus disease 2019 (COVID-19) vaccination across varying causes of immunodeficiency. METHODS: Prospective study of fully vaccinated immunocompromised adults (solid organ transplant [SOT], hematologic malignancy, solid cancers, autoimmune conditions, human immunodeficiency virus [HIV]) versus nonimmunocompromised healthcare workers (HCWs). The primary outcome was the proportion with a reactive test (seropositive) for immunoglobulin G to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain. Secondary outcomes were comparisons of antibody levels and their correlation with pseudovirus neutralization titers. Stepwise logistic regression was used to identify factors associated with seropositivity. RESULTS: A total of 1271 participants enrolled: 1099 immunocompromised and 172 HCW. Compared with HCW (92.4% seropositive), seropositivity was lower among participants with SOT (30.7%), hematological malignancies (50.0%), autoimmune conditions (79.1%), solid tumors (78.7%), and HIV (79.8%) (P < .01). Factors associated with poor seropositivity included age, greater immunosuppression, time since vaccination, anti-CD20 monoclonal antibodies, and vaccination with BNT162b2 (Pfizer) or adenovirus vector vaccines versus messenger RNA (mRNA)-1273 (Moderna). mRNA-1273 was associated with higher antibody levels than BNT162b2 or adenovirus vector vaccines after adjusting for time since vaccination, age, and underlying condition. Antibody levels were strongly correlated with pseudovirus neutralization titers (Spearman r = 0.89, P < .0001), but in seropositive participants with intermediate antibody levels, neutralization titers were significantly lower in immunocompromised individuals versus HCW. CONCLUSIONS: Antibody responses to COVID-19 vaccines were lowest among SOT and anti-CD20 monoclonal recipients, and recipients of vaccines other than mRNA-1273. Among those with intermediate antibody levels, pseudovirus neutralization titers were lower in immunocompromised patients than HCWs. Additional SARS-CoV-2 preventive approaches are needed for immunocompromised persons, which may need to be tailored to the cause of immunodeficiency.

Bilateral tibial fractures associated with powered exoskeleton use in complete spinal cord injury - a case report & literature review.

INTRODUCTION: Powered robotic exoskeleton (PRE) physiotherapy programmes are a relatively novel frontier which allow patients with reduced mobility to engage in supported walking. Research is ongoing regarding their utility, risks, and benefits. This article describes the case of two fractures occurring in one patient using a PRE. CASE: We report the case of a 54 year old man who sustained bilateral tibial fractures while using a PRE, on a background of T10 AIS A SCI. The initial session was discontinued due to acute severe bilateral knee swelling after approximately 15 min. The patient attended their local hospital the following day, where radiographs demonstrated bilateral proximal tibial fractures. The patient was treated with manipulation under anaesthetic and long-leg casting for five weeks, at which point he was stepped down to hinged knee braces which were weaned gradually while he remained non-weight bearing for 12 weeks. The patient was investigated with DEXA scan and was diagnosed with osteoporosis. He was liaised with rheumatology services and bone protection was initiated. Fracture healing was achieved and weight-bearing precautions were discontinued, however this period of immobilisation led to significant spasticity. The patient was discharged from orthopaedic services, with ongoing rehabilitation and physiotherapy follow-up. CONCLUSION: PRE assisted physiotherapy programmes are a promising concept in terms of rehabilitation and independence, however they are not without risk and it is important that both providers and patients are aware of this. Furthermore, SCI patients are at increased risk for osteoporosis and should be monitored and considered for bone protection.

Readability of Online Information on Core Decompression of the Hip for Avascular Necrosis.

Introduction Avascular necrosis (AVN) of the femoral head is a type of osteonecrosis, which is caused by the disruption of blood flow to the proximal femur, resulting in osteocyte death. Regression of the disease is rare, and most patients will ultimately progress to having a total hip arthroplasty performed. Early diagnosis of AVN allows treatment options beyond total hip arthroplasty. One such procedure described is core decompression of the femoral head. Health literacy is defined as the ability to make health decisions in the context of everyday life. It has been shown that lower levels of health literacy are associated with higher complication rates. It has been recommended that patient information documents are written at a reading grade level (RGL) no higher that the sixth grade to help with health literacy. Methods Twenty-nine websites containing information on core decompression were identified, and the online readability software WebFX (Pennsylvania, USA) was used to carry out analysis on readability. This software was able to generate a Flesch reading ease score (FRES) and an RGL for each website. The search was carried out in the Republic of Ireland. Results The mean FRES score was 48.8 (standard deviation (SD) +/-15.3), which categorizes the data as "difficult to read." The mean RGL was 8.46 (SD +/-2.34), which is higher than the recommended target. Conclusion This study has shown that the material on the Internet regarding core decompression is above the recommended readability levels for the majority of patients. This aligns with results from similar studies that have assessed the readability of online patient information. Given these outcomes, it is imperative for physicians to take an active role in curating and delivering information to their patients, ensuring that it is comprehensible. This approach aims to empower patients with a clearer understanding of core decompression, enabling them to make more informed decisions about their health.

'Out of hours' orthopaedics in an Irish regional trauma unit and the impact of COVID-19.

INTRODUCTION: MRHT is the regional trauma service for the Midlands, providing 24/7 orthopaedic cover. 'Out of hours' surgery is reserved for those occasions where waiting for the next operating list during normal working hours would result in an unacceptable outcome for the patient. AIMS: To identify how many 'out-of-hours' surgeries were performed and what proportion of the total workload was made up by these cases. Secondly, to identify the impact of COVID-19 on our workload as an acute trauma service. METHODS: We performed a retrospective analysis of all operations performed in the emergency orthopaedic theatre between January 2017 and October 2020. Included were all emergency orthopaedic procedures performed after 6 p.m. and before 8 a.m. We compared this to the total number of trauma surgeries performed in the same time period to calculate the percentage of our total operations. RESULTS: There were a total of 7615 orthopaedic trauma operations performed in the 193 weeks. 164 of these were 'out-of-hours'. This represents 2.2% of the total operations performed and is equal to 0.84 cases per week. 55 of the 164 (33.5%) were performed in children under the age of 18. 62 were performed between 6 and 8 p.m., 61 between 8 and 10 p. m., 31 between 10 p.m. and midnight, and the remaining 10 were performed between midnight and 3 a.m. CONCLUSION: Surgery out of hours has been associated with increased complications, and so decisions to perform emergency surgery should not be made lightly. However, sometimes they are unfortunately necessary and are some of the most important operations we can perform as orthopaedic surgeons.

Surgical management strategies for colorectal malignancies of the splenic flexure - A systematic review and network meta-analysis.

BACKGROUND: Extended right hemicolectomy (ERHC) or left hemicolectomy (LHC) are accepted as the standard-of-care for colonic tumours of the splenic flexure. Lymphatic drainage at this site is poorly defined and subject to significant heterogeneity. Nevertheless, emerging evidence demonstrates the potential oncological safety of segmental splenic flexure colectomy (SFC). AIM: To perform a systematic review and network meta-analysis (NMA) to compare outcomes following ERHC, LHC and SFC for splenic flexure tumours (SFTs). METHODS: A systematic review was performed as per PRISMA guidelines. NMA was performed using R Shiny and Netmeta packages. RESULTS: A total of 13 studies, involving 6176 patients (ERHC n = 785; LHC n = 1527; SFC n = 3864) were included in the NMA. There was no difference in overall survival (OS) (SFC vs LHC Hazard Ratio [HR] 1.0, 95% Credible Interval [CrI] 0.76,1.34; SFC vs ERHC HR 1.18, 95% CrI 0.85,1.58) between the groups. SFC had a shorter operation time (Mean 176.37 min; Mean Difference [MD] SFC vs LHC 20.34 min 95% CrI 10.9, 29.97; SFC vs ERHC MD 22.19 95% CrI 11.09, 33.29) but also had a lower average lymph node yield (LNY) compared with ERHC (MD 7.15, 95% CrI 5.71, 8.60). ERHC had a significantly higher incidence of post-operative ileus (Odds Ratio [OR] 3.47, 95% CrI 1.11, 10.84). There was also no difference observed for minimally invasive approaches, anastomotic leak rate, perioperative mortality, reoperation rates or length of stay. CONCLUSIONS: While SFC may allow for reduced operative duration and improved bowel function postoperatively. SFC, LHC, ERHC are all acceptable approaches for curative resection of cancers of the splenic flexure, with no difference in OS observed. Thus, surgeon preference and candidate-specific factors will likely determine the management of SFTs.

Dual Intra-Articular Fracture of the Body and Hook of Hamate: A Delayed Presentation.

Fractures of the hamate bone are an unusual clinical entity. Dual fractures involving both the body and the hook of the hamate are even more unique, with only two previous cases described in the literature, to our knowledge. Clinicians are often unfamiliar with the presenting signs of this unusual injury, and subsequently, diagnosis is often delayed or missed entirely. We describe the case of a 19-year-old male who sustained an intra-articular body of hamate fracture with an ipsilateral hook of hamate fracture in his dominant hand. He presented 10 days following the initial injury and was managed with open reduction and internal fixation (ORIF).

Third and fourth generation ceramic-on-ceramic total hip arthroplasty at a minimum of ten years.

Background: Ceramic on Ceramic bearings in Total Hip Arthroplasty (THA) afford a low friction coefficient, low wear rates and extreme hardness. Significant complications include hip squeak, ceramic fracture and poor polyethylene performance in revision procedures due to imbedding of abrasive microscopic ceramic fragments. We report on the results of this bearing at a minimum of 10 years. Methods: A single-centre retrospective review of 449 THAs was performed. Primary outcome measures included aseptic revision and all-cause revision rates at a minimum of 10 years post operatively. Evaluation of functionality was performed with WOMAC and SF-36 scores which were performed pre-operatively and at intervals of 6 months, one year, 2 years, 5 years and 10 years post operatively. Results: There was a 6.2% (n = 28) all-cause and 5.3% (n = 24) aseptic revision rate for ceramic on ceramic total hip arthroplasty at minimum of 10 years with a mean time to revision 4.8 years (range 2 months-11.6 years). Notably, there were 2 revisions for ceramic head fracture, one for ceramic liner fracture, 3 for aseptic loosening and 3 revisions for squeaking. Pain of unknown origin was the most common reason for revision. There was an improvement in postoperative WOMAC scores from a mean of 59.8 (range 15-95) pre-operatively to a mean of 15.6 (range 0-78) at 10 years. Conclusion: This study showed good functional outcomes but high revision rates for CoC THA at a minimum of 10 years. Our rates of ceramic fracture were consistent with other studies.

Erysipelothrix rhusiopathiae Prosthetic Joint Infection in an Immunocompromised Patient: A Case Report.

CASE: We report the case of an immunosuppressed 65-year-old man with prosthetic joint infection (PJI) 23 years postoperatively because of Erysipelothrix rhusiopathiae, through hematogenous seeding of cutaneous erysipeloid. Immunotherapy was discontinued, washout was performed, and antimicrobial therapy was guided by laboratory sensitivities. The patient was discharged on suppressive oral ciprofloxacin monotherapy. First-stage revision was performed at 5 months after presentation-subsequent aspiration at 1 year postoperatively demonstrated no organisms and no leucocytes. At 18-month follow-up, the patient continues to do well and has elected not to proceed with second-stage surgery. CONCLUSION: E. rhusiopathiae is a rarely seen pathogen in PJI-it should be considered with immunosuppression and relevant exposure risks. The patient achieved good clinical outcome and has experienced no sequelae to date.

The use of bioabsorbable compression screws & polyethylene tension band for fixation of displaced olecranon fractures.

INTRODUCTION: Transverse fractures of the olecranon are commonly fixed using tension-band wiring techniques. However the superficial nature of this area leads to high complication rates requiring removal of metalwork. The purpose of this retrospective study is to report and evaluate functional outcomes of polyethylene tension-band and bioabsorbable Magnesium alloy screw fixation of olecranon fractures. METHODS: A retrospective case-control study was undertaken. Demographics, injury type and post-operative details were collected. All patients were treated in the same institution by a single surgeon. Primary outcomes included radiographic healing and post-operative range of motion. Secondary outcome was post-operative complications. RESULTS: A total of five cases were identified. Mean age was 52.4. The control group was made up of six patients treated with a traditional tension band wire fixation. One patient in study group was lost to follow up. 80% of fractures in study group demonstrated anatomic post-operative radiographic union, compared with 83% of control group. All patients had range of motion above 100°, with full protonation and supination. One patient did have an extension lag of 15°. CONCLUSION: Surgical repair of olecranon fractures is often complicated by the need for re-operation. This method provides both intramedullary fixation and conversion of distraction forces to compression forces with bioabsorbable materials, and aims to reduce the high re-operation rates commonly seen by avoiding the use of permanent indwelling metal hardware.

Timing of surgical fixation in traumatic spinal fractures.

AIMS: The timing of surgical fixation in spinal fractures is a contentious topic. Existing literature suggests that early stabilization leads to reduced morbidity, improved neurological outcomes, and shorter hospital stay. However, the quality of evidence is low and equivocal with regard to the safety of early fixation in the severely injured patient. This paper compares complication profiles between spinal fractures treated with early fixation and those treated with late fixation. METHODS: All patients transferred to a national tertiary spinal referral centre for primary surgical fixation of unstable spinal injuries without preoperative neurological deficit between 1 July 2016 and 20 October 2017 were eligible for inclusion. Data were collected retrospectively. Patients were divided into early and late cohorts based on timing from initial trauma to first spinal operation. Early fixation was defined as within 72 hours, and late fixation beyond 72 hours. RESULTS: In total, 86 patients underwent spinal surgery in this period. Age ranged from 16 to 88 years. Mean Injury Severity Score (ISS) was higher in the early stabilization cohort (p = 0.020). Age was the sole significant independent variable in predicting morbidity on multiple regression analysis (p < 0.003). There was no significant difference in complication rates based on timing of surgical stabilization (p = 0.398) or ISS (p = 0.482). CONCLUSION: Our results suggest that these patients are suitable for early appropriate care with spinal precautions and delayed definitive surgical stabilization. Earlier surgery conferred no morbidity benefit and had no impact on length of stay. Cite this article: Bone Joint J 2020;102-B(5):627-631.

Outcomes of the Exeter V40 cemented femoral stem at a minimum of ten years in a non-designer centre.

AIMS: The Exeter V40 cemented femoral stem was first introduced in 2000. The largest single-centre analysis of this implant to date was published in 2018 by Westerman et al. Excellent results were reported at a minimum of ten years for the first 540 cases performed at the designer centre in the Exeter NHS Trust, with stem survivorship of 96.8%. The aim of this current study is to report long-term outcomes and survivorship for the Exeter V40 stem in a non-designer centre. METHODS: All patients undergoing primary total hip arthroplasty using the Exeter V40 femoral stem between 1 January 2005 and 31 January 2010 were eligible for inclusion. Data were collected prospectively, with routine follow-up at six to 12 months, two years, five years, and ten years. Functional outcomes were assessed using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores. Outcome measures included data on all components in situ beyond ten years, death occurring within ten years with components in situ, and all-cause revision surgery. RESULTS: A total of 829 stems in 745 patients were included in the dataset; 155 patients (20.8%) died within ten years, and of the remaining 664 stems, 648 stems (97.6%) remained in situ beyond ten years. For the 21 patients (2.5%) undergoing revision surgery, 16 femoral stems (1.9%) were revised and 18 acetabular components (2.2%) were revised. Indications for revision in order of decreasing frequency were infection (n = 6), pain (n = 6), aseptic component loosening (n = 3), periprosthetic fracture (n = 3), recurrent dislocation (n = 2), and noise production (ceramic-on-ceramic squeak) (n = 1). One patient was revised for aseptic stem loosening. The mean preoperative WOMAC score was 61 (SD 15.9) with a mean postoperative score of 20.4 (SD 19.3) (n = 732; 88.3%). CONCLUSION: The Exeter V40 cemented femoral stem demonstrates excellent functional outcomes and survival when used in a high volume non-designer centre. Outcomes are comparable to those of its serially validated predecessor, the Exeter Universal stem.Cite this article: Bone Jt Open 2020;1-12:743-748.

Effects of the overexpression of a soybean cytosolic glutamine synthetase gene (GS15) linked to organ-specific promoters on growth and nitrogen accumulation of pea plants supplied with ammonium.

A soybean cytosolic glutamine synthetase gene (GS15) fused to a constitutive promoter (CaMV 35S), a putative nodule-specific promoter (LBC(3)), or a putative root-specific promoter (rolD) was transformed into Pisum sativum L. cv. Greenfeast. Four lines with single copies (Lines 1, 7, 8 and 9) and four lines with two copies each of GS15 (Lines 2, 4, 6 and 11) were compared to the wild-type (WT) parental line for levels of cytosolic glutamine synthetase (GS1), glutamine synthetase (GS) activity, N accumulation, N derived form the atmosphere (NDFA), and biomass of plants grown on 0.0, 0.1, 1.0 or 10.0 mM NH(4)(+). Enhanced levels of GS1 were detected in leaves of one of the two lines transformed with the 35S-GS15 construct, and all three lines containing the rolD-GS15 construct. All three lines containing the LBC(3)-GS15 construct had increased levels of GS1 in nodules. Despite the increased levels of GS1 in many transformants, only the roots of lines containing the rolD-GS15 construct consistently demonstrated enhanced levels of GS activity (up to 12-fold). Positive responses in plant N content, NDFA, and biomass were rare, but increases in plant biomass and N content of up to 17% and 54%, respectively, occurred in some of the rolD-GS15 lines at certain levels of ammonium. In general, GS15 copy number did not seem to differentially affect phenotype of the transformants, and transformants respond to ammonium concentrations in similar patterns to that previously observed with nitrate. Despite the fact that the rolD-GS15 transformants consistently resulted in increased GS activity in roots and resulted in some occurrences of increases in biomass and plant N content, the lack of consistent positive growth effect across all transformants indicates that the generalized overexpression of GS1 in tissues holds little potential for positive growth responses in pea.

Field assessment of outcrossing from transgenic pea (Pisum sativum L.) plants.

The frequency of outcrossing from a transgenic line of peas into three cultivars ('Carneval', 'Montana', 'Tipu') was studied in the field in 1997 and 1999. Two dominant traits, normal leaf form and a highly-expressed beta-glucuronidase (gusA) gene, were used as markers of pollen transfer. Because of heterogeneity in the commercial seed sources, leaf form alone was unreliable for assessing pollen migration into 'trap' plants. Of approximately 9000 offspring tested, only five plants scored positive for the presence of both markers. All five were located in 'trap' plots situated near the transgenic line. This represents a mean outcrossing rate of 0.07%.

Intraneural nodular fasciitis: case report and literature review.

Nodular fasciitis is a benign or reactive myofibroblastic soft tissue tumor that occurs most frequently in the forearm but has been reported throughout the body. Nodular fasciitis has not been reported to arise within a peripheral nerve, and we present a case of intraneural nodular fasciitis within the ulnar nerve at the distal forearm. Preoperative symptoms of advanced ulnar neuropathy resolved completely after intraneural dissection and subtotal resection of the tumor.

Overexpression of a soybean cytosolic glutamine synthetase gene linked to organ-specific promoters in pea plants grown in different concentrations of nitrate.

A glutamine synthetase gene ( GS15) coding for soybean cytosolic glutamine synthetase (GS1) fused to a constitutive promoter (CaMV 35S), a putative nodule-specific promoter (LBC(3)) and a putative root-specific promoter (rolD) was transformed into Pisum sativum L. cv. Greenfeast. Four lines with single copies of GS15 (one 35S-GS15 line, one LBC (3) -GS15 line, and two rolD-GS15 lines) were tested for the expression of GS15, levels of GS1, GS activity, N accumulation, N(2) fixation, and plant growth at different levels of nitrate. Enhanced levels of GS1 were detected in leaves of three transformed lines (the 35S-GS15 and rolD-GS15 transformants), in nodules of three lines (the LBC (3) -GS15 and rolD-GS15 transformants), and in roots of all four transformants. Despite increased levels of GS1 in leaves and nodules, there were no differences in GS activity in these tissues or in whole-plant N content, N(2) fixation, or biomass accumulation among all the transgenic lines and the wild-type control. However, the rolD-GS15 transformants, which displayed the highest levels of GS1 in the roots of all the transformants, had significantly higher GS activity in roots than the wild type. In one of the rolD-GS15 transformed lines (Line 8), increased root GS activity resulted in a lower N content and biomass accumulation, supporting the findings of earlier studies with Lotus japonicus (Limami et al. 1999 ). However, N content and biomass accumulation was not negatively affected in the other rolD-GS15 transformant (Line 9) and, in fact, these parameters were positively affected in the 0.1 mM treatment. These findings indicate that overexpression of GS15 in various tissues of pea does not consistently result in increases in GS activity. The current study also indicates that the increase in root GS activity is not always consistent with decreases in plant N and biomass accumulation and that further investigation of the relationship between root GS activity and growth responses is warranted.