The assembly of neutrophil inflammasomes during COVID-19 is mediated by type I interferons.

The severity of COVID-19 is linked to excessive inflammation. Neutrophils represent a critical arm of the innate immune response and are major mediators of inflammation, but their role in COVID-19 pathophysiology remains poorly understood. We conducted transcriptomic profiling of neutrophils obtained from patients with mild and severe COVID-19, as well as from SARS-CoV-2 infected mice, in comparison to non-infected healthy controls. In addition, we investigated the inflammasome formation potential in neutrophils from patients and mice upon SARS-CoV-2 infection. Transcriptomic analysis of polymorphonuclear cells (PMNs), consisting mainly of mature neutrophils, revealed a striking type I interferon (IFN-I) gene signature in severe COVID-19 patients, contrasting with mild COVID-19 and healthy controls. Notably, low-density granulocytes (LDGs) from severe COVID-19 patients exhibited an immature neutrophil phenotype and lacked this IFN-I signature. Moreover, PMNs from severe COVID-19 patients showed heightened nigericin-induced caspase1 activation, but reduced responsiveness to exogenous inflammasome priming. Furthermore, IFN-I emerged as a priming stimulus for neutrophil inflammasomes. These findings suggest a potential role for neutrophil inflammasomes in driving inflammation during severe COVID-19. Altogether, these findings open promising avenues for targeted therapeutic interventions to mitigate the pathological processes associated with the disease.

Reduction in mucosal-associated invariant T cells (MAIT) in APECED patients is associated with elevated serum IFN-γ concentration.

Mucosal-associated invariant T cells (MAIT) are innate-like lymphocytes enriched in mucosal organs where they contribute to antimicrobial defense. APECED is an inborn error of immunity characterized by immune dysregulation and chronic mucocutaneous candidiasis. Reduction in the frequency of circulating MAITs has been reported in many inborn errors of immunity, but only in a few of them, the functional competence of MAITs has been assessed. Here, we show in a cohort of 24 patients with APECED, that the proportion of circulating MAITs was reduced compared with healthy age and sex-matched controls (1.1% vs. 2.6% of CD3+ T cells; p < 0.001) and the MAIT cell immunophenotype was more activated. Functionally the IFN-γ secretion of patient MAITs after stimulation was comparable to healthy controls. We observed in the patients elevated serum IFN-γ (46.0 vs. 21.1 pg/mL; p = 0.01) and IL-18 (42.6 vs. 13.7 pg/mL; p < 0.001) concentrations. Lower MAIT proportion did not associate with the levels of neutralizing anti-IL-22 or anti-IL-12/23 antibodies but had a clear negative correlation with serum concentrations of IFN-γ, IL-18, and protein C-reactive protein. Our data suggest that reduction of circulating MAITs in patients with APECED correlates with chronic type 1 inflammation but the remaining MAITs are functionally competent.

Incidences and Outcomes of Operatively Treated Interprosthetic Femoral Fractures Compared to Vancouver Type C and Rorabeck Type II Fractures.

BACKGROUND: This case-control study evaluated the incidences and outcomes of interprosthetic femoral fracture (IPFF) (Group I) and performed comparisons with Vancouver type C (Group II) and Rorabeck type II (Group III) periprosthetic femoral fractures (PPFF) occurring at similar anatomic sites. METHODS: A retrospective analysis was performed for all patients who had a previously implanted total hip arthroplasty (THA) and total knee arthroplasty (TKA), who lived in the hospital district and had undergone surgery due to PPFF. A total of 153 PPFFs [Group I (n = 31), Group II (n = 21), and Group III (n = 108)] were included. The annual incidences of PPFFs were summarized per 100,000 individuals. The risks of complications, reoperations, and mortalities were evaluated for all groups. RESULTS: The mean population-based annual incidence was 0.9 per 100,000 person years for Group I, 0.7 per 100,000 person years for Group II, and 3.1 per 100,000 person years for Group III. A total of 25 of 153 (16%) major complications were found and 23 of 153 (13%) cases resulted in a revision surgery. The cumulative incidence of death in Group I was 50.4% at 10 years, in Group II it was 63.8% at 10 years, and in Group III it was 74.9% at 10 years. CONCLUSION: The annual incidence of the IPFF almost doubled while the incidence of Vancouver type C stayed stable and Rorabeck type II incidence increased 5-fold. Most of the major complications occurred in IPFF group, while Rorabeck type II patients had the worst survival.

Long-term survival of resurfacing humeral hemiarthroplasty.

INTRODUCTION: The indication for shoulder resurfacing arthroplasty is controversial, and survival of these implants is somewhat inconsistent. This study aimed to evaluate the long-term survivorship of resurfacing humeral head implants (RHHIs) and determine risk factors for complications and revisions. MATERIALS AND METHODS: This retrospective cohort study consisted of 275 cases and two types of RHHIs. The survival rate was evaluated using the Kaplan-Meier method and Cox regression for risk factor analysis. Demographic factors were studied, and the change in the humerus centre of rotation (COR) was measured. RESULTS: The mean follow-up time was 8.7 years (SD 2.7 months, range 2.8-15.9 years). The mean age of the patients was 67.6 years (SD 9.6, range 33.5-84.9). Ten-year cumulative RHHI survival was 94.1%. The cumulative estimate without any complication was 98.9% at 5 years, 80.0% at 10 years and at 15 years it was 61.5%. The most common complication was persistent pain in 13.8% of the RHHIs. The risk factors for complications and revisions were implant type, preoperative conditions and change of COR > 5 mm. CONCLUSIONS: RRHIs showed excellent long-term survival, but many complications were found. The most common complication was persistent pain, which seemed to be caused by a change of COR and was more related to one type of implant.

Short-term primary and revision modular dual-mobility cup total hip arthroplasty outcomes in high-risk dislocation patients: a retrospective study.

PURPOSE: Modular dual-mobility cups (MDMCs) have a lower risk for dislocation after total hip arthroplasty (THA). The primary aims of our study were to analyze implant survivorship and to determine complications, especially dislocation, and revision rates of primary THAs used for hip fracture patients and for revision THAs. Secondary aims were to evaluate mortality after MDMC surgery and to find out if introduction of MDMC at our institution (Kuopio University Hospital, Finland) have decreased dislocation rate. METHODS: This retrospective cohort study consisted of 101 MDMC patients who were consecutively operated at our institution between April 1, 2018 and June 30, 2020. The implant survival rate, complications and mortality were evaluated with minimum of 2-year follow-up. Finnish Hospital Discharge Register was used to find out yearly dislocation rates following THA at our institution. RESULTS: The cumulative estimate implant survival after MDMC in the primary THA group was 97% at 2 years, and in the revision THA group, it was 90% at 2 years. Dislocation was a rare complication in the primary THA group (1.4%), while it was common in revision THA group (12.9%). The cumulative estimate for mortality after MDMC in the primary THA group was 13% at 2 years, and in the revision group, it was also 13% at 2 years. The yearly number of patients who had re-hospitalization period due to THA dislocation decreased 46% after implementation of MDMC. CONCLUSION: Short-term survival and complication rates after MDMC were excellent after primary THA and moderate after revision THA. Implementation of MDMC THA for hip fracture patients seems to have effectively decrease dislocation rate during a short follow-up.

Superspreading of SARS-CoV-2 Omicron BA.2.23 among vaccinated Finnish adults: symptomatic COVID-19 only contracted by those without recent infection.

An outbreak of SARS-CoV-2 was confirmed after an academic party in Helsinki, Finland, in 2022. All 70 guests were requested to fill in follow-up questionnaires; serologic analyses and whole-genome sequencing (WGS) were conducted when possible.Of those participating - all but one with ≥3 vaccine doses - 21/53 (40%) had test-confirmed symptomatic COVID-19: 7% of those with earlier episodes and 76% of those without. Half (11/21) were febrile, but none needed hospitalisation. WGS revealed subvariant BA.2.23.Compared to vaccination alone, our data suggest remarkable protection by hybrid immunity against symptomatic infection, particularly in instances of recent infections with homologous variants.

How Often Do Complications and Mortality Occur After Operatively Treated Periprosthetic Proximal and Distal Femoral Fractures? A Register-based Study.

BACKGROUND: The incidence of periprosthetic femoral fractures is increasing because of an increasing number of primary THAs and TKAs. High rates of complications and mortality are associated with periprosthetic fractures, but few studies have evaluated and compared the population-based incidences of these events after fractures. QUESTIONS/PURPOSES: (1) What is the annual incidence of periprosthetic fractures treated with surgery in one hospital district in Finland? (2) How are those incidences changing over time? (3) What is the risk of complications, reoperations, and death after those injuries? METHODS: This register-based study evaluated 2259 patients who underwent revision THA or TKA or any surgery for a femoral fracture between January 2004 and December 2016 at the only hospital in our district where these types of operations are performed. During the study period, the diagnosis and operation codes of the operated-on patients varied greatly, and they were somewhat inaccurate. We thus evaluated radiographs of all 2259 patients one by one, and created inclusion and exclusion criteria based on radiologic findings and medical records. Of those, 12% (279 of 2259) had periprosthetic fractures that met the inclusion criteria, and from these, we formed two study groups (periprosthetic proximal femur fractures, n = 171; periprosthetic distal femur fractures, n = 108). Eighty-eight percent (1980 of 2259) of the patients were excluded because they were treated for a condition other than periprosthetic femoral fracture. The follow-up period ended in December 2019 or at the time the patient died. To evaluate the population-based incidence, we drew the number of individuals with THA or TKA in the hospital district from the Finnish Arthroplasty Register and the Finnish Hospital Discharge Register. The characteristics of patients with operatively treated periprosthetic femoral fractures were evaluated in terms of age, gender, fracture type, implant type, and time from the index operation to periprosthetic fracture. The annual incidences of periprosthetic femoral fractures are summarized per 1000 person-years of individuals living with an implanted THA or TKA and per 100,000 individuals per year living in our hospital district. The risks of death, complications, and reoperations were evaluated for both groups, and comparisons were made in terms of patient characteristics. RESULTS: The mean annual incidence of operatively treated periprosthetic proximal femur fractures per 1000 people living with THA implants was 2.3 ± 0.9 (95% confidence interval 1.8 to 2.7) per year, and for those with periprosthetic distal femur fractures with TKA implants, it was 1.3 ± 0.6 (95% CI 1.0 to 1.7). There was an increasing trend in the incidence of periprosthetic proximal femur fractures from 1.6 to 3.8 (95% CI 1.8 to 2.8) per 1000 arthroplasties, and it increased from 0.4 to 1.7 (95% CI 2.4 to 4.4) for periprosthetic distal femur fractures between 2004 and 2016. The mean population-based incidence of periprosthetic proximal femur fractures per 100,000 person-years was 5.3 ± 2.2 (95% CI 4.1 to 6.4) per year, and for periprosthetic distal femur fractures, it was 3.4 ± 1.7 (95% CI 2.5 to 4.4). The incidence of periprosthetic proximal femur fractures related to 100,000 person-years increased from 3.2 to 8.9 (95% CI 3.9 to 6.6), while the incidence of periprosthetic distal femur fractures increased from 1.3 to 4.4 (95% CI 2.4 to 4.8) during the study period. The cumulative incidence of major complications after periprosthetic proximal femur fracture was 8.8% at 1 year (95% CI 5.1% to 13.6%) and 12.3% at 10 years (95% CI 7.5% to 18.4%), and after periprosthetic distal femur fracture, it was 7.4% at 1 year (95% CI 3.5% to 13.4%) and 9.3% at 10 years (95% CI 4.7% to 15.7%). The cumulative incidence of reoperation after periprosthetic proximal femur fracture was 10.5% at 1 year (95% CI 6.5% to 15.7%) and 13.5% at 10 years (95% CI 8.9% to 19.1%), and for periprosthetic distal femur fracture, it was 8.3% at 1 year (95% CI 4.1% to 14.5%) and 13.8% at 10% years (95% CI 7.8% to 21.4%). The cumulative incidence of death after periprosthetic proximal femur fracture was 8.2% at 1 year (95% CI 4.7% to 12.9%) and 47.3% at 10 years (95% CI 38.1% to 55.9%), and after periprosthetic distal femur fractures, it was 14.8% at 1 year (95% CI 8.8% to 22.2%) and 67.8% at 10 years (95% CI 56.3% to 76.9%). CONCLUSION: The increased use of THA and TKA has led to an increase in the incidence of operatively treated periprosthetic fractures, which means there will be more revisions in the future. Older age, frailty of these patients, and often-complicated fracture patterns are related to a high rate of complications, reoperations, and mortality. Healthcare systems must prepare for a large increase in revisions for periprosthetic fracture, which are morbid events for patients and costly ones for healthcare systems. LEVEL OF EVIDENCE: Level III, therapeutic study.

Long-term survival analysis of cementless large-diameter head metal-on-metal total hip arthroplasty.

INTRODUCTION: The aim of this retrospective study was to study the long-term survival and reasons for revisions of a single-type, large-diameter head (LDH) metal-on-metal (MoM) implant. A special study interest was to find the threshold level for revision in terms of adverse reaction to metal debris (ARMD). MATERIALS AND METHODS: In this cohort study, we retrospectively reviewed 234 patients (253 hips) who received 38 mm head size LDH MoM total hip arthroplasties (THAs) between 01 January 2004 and 31 December 2009 at our institution. Patient symptoms, conventional radiographs, magnetic resonance imaging (MRI) findings and whole blood metal ions were studied. RESULTS: The median follow-up time was 11.5 years. The Kaplan-Meier cumulative survival estimate of the implant was 89.6% at 10 years and 82.9% at 14.6 years. Overall, 34/253 (13.4%) hips were revised during the follow-up period and of these; 19/34 (55.9%) were revised due to ARMD. The prevalence of ARMD was 12.4% (29/234 patients). CONCLUSIONS: The survival of the implant was on a moderate level as the 10-year cumulative survival rate was 89.6%. The exact threshold level for ARMD revision cannot be determined due to multiple variables affecting factors in re-operation decision-making.

Intra- and inter-observer agreement in distal radius fracture dislocation measurement of casting position.

BACKGROUND AND PURPOSE: Most displaced distal radius fractures (DRF) are treated nonoperatively, with reduction and immobilization in a cast. Studies assessing intra- or inter-observer agreement on radiologic measurements of casting position have not been published, which was the aim of our study. PATIENTS AND METHODS: Our study is based on the Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) study. All detected DRFs during the OSTPRE follow-up were retrieved and based on sample size calculations 50 fractures were randomly selected for the study. 5 independent reviewers measured dislocation parameters and wrist position in a cast from the radiographs. A linear mixed model was used to estimate the concordance correlation coefficient (CCC) and total deviance index (TDI) that were used to evaluate intra- and inter-observer agreement. We used Kappa values to determine intra- and inter-rater agreement on radiographically acceptable reduction of the DRF. Limits of acceptable position were those defined by Finnish Current Care Guidelines. RESULTS: For radial inclination, radial shortening, and dorsal/volar tilt, intra- and inter-observer correlations were high (CCC > 0.76). In addition, measurements of wrist angle in a splint had high correlations (CCC > 0.78), whereas measurement of intra-articular gap and step had poor correlations (CCC < 0.52). The Kappa value for overall agreement on the radiographically acceptable position of the DRF was modest (0.59). CONCLUSION: Intra- and inter-observer repeatability of casting position of radial inclination, radial shortening, and dorsal/volar tilt were high whereas intra-articular gap and step had poor correlations.

Charlson comorbidity index predicts the 10-year survivorship of the operatively treated hip fracture patients.

PURPOSE: The aim of this study was to determine how Charlson comorbidity index (CCI) predicts the 10-year survival of operatively treated hip fracture patients aged ≥ 65 years. METHODS: This retrospective cohort study included all consecutive patients who had a hip fracture and were operatively treated upon in the study period from 01 January 2007 to 31 December 2007 at the university hospital. The clinical patient data were obtained from the medical records, and CCI score was calculated. The CCI predicts the 10-year mortality for a patient who may have a range of 22 comorbid conditions. Cumulative survival and complications were evaluated in terms of gender. RESULTS: A total of 241 hip fractures were studied; of these, 183/241 (76%) were females. A total of 32/241 (15%) complications were found, of which 26/241 (11%) were considered major. Overall, 213/241 (88%) patients died during the 10 years of follow-up. Cumulative survival estimates for females were 13% at 10 years (SE = 0.3, 95% CI 3.8-4.8), and for males, it was 12% at 10 years (SE = 0.5, 95% CI 2.8-4.6) (p = 0.33). CCI was significantly associated with mortality after the hip fracture as patients with CCI scores ≥ 4 were at a 3.1-8.5 times higher risk of death compared to patients with low CCI scores of 2-3 (p < 0.001). CONCLUSION: Complications are common after operatively treated hip fracture. Advanced age, living in a care facility, ASA class 4 and high CCI score ≥ 4 were risk factors of mortality after the operatively treated hip fracture.

Long-term follow-up results of medial opening wedge high tibia osteotomy with a pre-countered non-locking steel plate.

INTRODUCTION: This retrospective study investigated the long-term follow-up results of medial opening wedge high tibial osteotomy (MOWHTO) with a pre-countered non-locking steel plate implant (Puddu plate = PP) used for medial knee osteoarthrosis (OA) treatment. MATERIALS AND METHODS: Consecutive 70 MOWHTOs (66 patients) were performed between 01.01.2004 and 31.12.2008 with the mean follow-up time of 11.4 (SD 4.5; range 1.2-16.1) years. The Kaplan-Meier survival analysis was used to evaluate the cumulative survival of the implant in terms of age (< 50 years old and ≥ 50 years old) and gender. Adverse events were studied and Cox regression analysis was used to evaluate risk factors [age, gender, body mass index (BMI), preoperative mechanical axis, severity of OA, use of bone grafting or substitution and undercorrection of mechanical axis from varus to valgus] for revisions. RESULTS: The estimates for the cumulative survival with no need for TKA after MOWHTO were 86% at 5 years, 67% at 10 years and 58% at 16.1 years (SE 0.6, CI 95% 11.1-13.5). A total of 33/70 (47%) adverse events occurred and 38/70 (54%) knees required some revision surgery during the follow-up. Cox regression did not show any statistically significant risk factors for revision. CONCLUSIONS: The PP has feasible MOWHTO results with a cumulative survival of 67% at 10 years with no need for conversion to TKA. Many adverse events occurred and revision rate due to any reason was high. Age or gender did not have statistically significant differences in terms of survival.

Retrospective Population-Based Cohort Study of Incidence, Complications, and Survival of 202 Operatively Treated Periprosthetic Femoral Fractures.

BACKGROUND: The aim of this study is to investigate the population and primary total hip arthroplasty (THA)-based incidences, fracture types, complications, and survival of operatively treated periprosthetic femoral fracture (PFF). METHODS: This retrospective study reviewed 202 cases of operatively treated PFFs in a study period from January 2004 to December 2016. The Vancouver classification was used to classify PFFs. RESULTS: The incidence of PFF related to 1000 primary THAs per year was 2.7 (standard deviation 1.0, range 0.9-4.5) at a defined hospital district area during the study period. The mean population-based incidence of operatively treated PFFs raised from 1.6 to 4.5 per 100,000 person-years during the study period. The B1-type fracture was the most common fracture type in 71 of 202 (35%) of these PFFs. The cumulative incidence of re-revision was 10.9% at 1 year and 15.6% at 15 years (95% confidence interval [CI] 10.9-21.0). The cumulative incidence for other major complications was 6.4% at 1 year and 9.9% at 15 years (95% CI 5.9-15.0). The cumulative incidence of death after PFF was 7.4% at 1 year and 56.3% at 15 years (95% CI 41.3-68.8) during the follow-up time from January 1, 2004 to December 31, 2019. CONCLUSION: This country-specific study showed a 3-fold increasing trend in the incidence of operatively treated PFFs from 2004 to 2016 per 1000 THAs. The Vancouver type B1 fracture was the most common type. A high number of complications were associated with PFFs and 7.4% of the patients had died within 1 year after PFF surgery.

Early aseptic loosening of cementless monoblock acetabular components.

PURPOSE: Early aseptic loosening of cementless monoblock acetabular components is a rare complication of total hip arthroplasty (THA) and hip resurfacing arthroplasty (HRA). The purpose of this study was to evaluate the incidence and risk factors for early aseptic loosening of the cementless monoblock acetabular components. METHODS: This retrospective analysis consisted of 4,043 cementless hip devices (3,209 THAs and 834 HRAs). We identified 41 patients with early aseptic loosening of the acetabular component. A control group of 123 patients without acetabular component loosening was randomly selected. The demographic data and risk factors for loosening of the acetabular component were evaluated. The mean follow-up time was 4.6 years (range, 1.7-7.8). The end-point was acetabular revision. RESULTS: The incidence of early acetabular component loosening was 1.0 %. Mean time to revision was 1.2 years (SD 1.6, range 0.0-5.4). There was significantly more Dorr type A and C acetabular morphology in patients with early loosening (P = 0.014). The loosened components were implanted to more vertical (P < 0.001) and less anteverted (P = 0.001) position than those of the control group. Presence of acetabular dysplasia or acetabular component type did not associate to early loosening. CONCLUSIONS: Acetabular morphology (Dorr type A and C) and component positioning vertically and less anteverted were more common in patients with early aseptic loosening of cementless acetabular components. Suboptimal cup position most likely reflects challenges to obtain sufficient stability during surgery. We hypothesize that errors in surgical technique are the main reason for early loosening of monoblock acetabular components.

Risk factors for intraoperative calcar fracture in cementless total hip arthroplasty.

BACKGROUND AND PURPOSE: Intraoperative periprosthetic femoral fracture is a known complication of cementless total hip arthroplasty (THA). We determined the incidence of--and risk factors for--intraoperative calcar fracture, and assessed its influence on the risk of revision. PATIENTS AND METHODS: This retrospective analysis included 3,207 cementless THAs (in 2,913 patients). 118 intraoperative calcar fractures were observed in these hips (3.7%). A control group of 118 patients/hips without calcar fractures was randomly selected. The mean follow-up was 4.2 (1.8-8.0) years. Demographic data, surgical data, type of implant, and proximal femur morphology were evaluated to determine risk factors for intraoperative calcar fracture. RESULTS: The revision rates in the calcar fracture group and the control group were 10% (95% CI: 5.9-17) and 3.4% (CI: 1.3-8.4), respectively. The revision rate directly related to intraoperative calcar fracture was 7.6%. The Hardinge approach and lower age were risk factors for calcar fracture. In the fracture group, 55 of 118 patients (47%) had at least one risk factor, while only 23 of118 patients in the control group (20%) had a risk factor (p = 0.001). Radiological analysis showed that in the calcar fracture group, there were more deviated femoral anatomies and proximal femur bone cortices were thinner. INTERPRETATION: Intraoperative calcar fracture increased the risk of revision. The Hardinge approach and lower age were risk factors for intraoperative calcar fracture. To avoid intraoperative fractures, special attention should be paid when cementless stems are used with deviant-shaped proximal femurs and with thin cortices.

Neutralizing antibodies after the third COVID-19 vaccination in healthcare workers with or without breakthrough infection.

BACKGROUND: Vaccinations against the SARS-CoV-2 are still crucial in combating the ongoing pandemic that has caused more than 700 million infections and claimed almost 7 million lives in the past four years. Omicron (B.1.1.529) variants have incurred mutations that challenge the protection against infection and severe disease by the current vaccines, potentially compromising vaccination efforts. METHODS: We analyzed serum samples taken up to 9 months post third dose from 432 healthcare workers. Enzyme-linked immunosorbent assays (ELISA) and microneutralization tests (MNT) were used to assess the prevalence of vaccine-induced neutralizing antibodies against various SARS-CoV-2 Omicron variants. RESULTS: In this serological analysis we show that SARS-CoV-2 vaccine combinations of BNT162b2, mRNA-1273, and ChAdOx1 mount SARS-CoV-2 binding and neutralizing antibodies with similar kinetics, but with differing neutralization capabilities. The most recent Omicron variants, BQ.1.1 and XBB.1.5, show a significant increase in the ability to escape vaccine and infection-induced antibody responses. Breakthrough infections in thrice vaccinated adults were seen in over 50% of the vaccinees, resulting in a stronger antibody response than without infection. CONCLUSIONS: Different three-dose vaccine combinations seem to induce considerable levels of neutralizing antibodies against most SARS-CoV-2 variants. However, the ability of the newer variants BQ1.1 and XBB 1.5 to escape vaccine-induced neutralizing antibody responses underlines the importance of updating vaccines as new variants emerge.

During the COVID-19 pandemic, mass vaccination efforts against SARS-CoV-2 infection have provided effective protection against the virus and helped reduce the severity of symptoms in infected individuals. However, it is not well established whether the existing vaccines can provide the same protection against new and emerging SARS-CoV-2 variants that develop over time as the virus evolves. In this study, we tested combinations of three-dose COVID-19 vaccines given in random order to protect against all SARS-CoV-2 variants in circulation including the newest being Omicron variants. We demonstrate that more than half of the population who received the three-dose vaccine combinations were infected with SARS-CoV-2 Omicron variants after receiving the last vaccine dose. These findings indicate the need to develop new vaccine candidates against emerging SARS-CoV-2 variants.

Stable Levels of Antibodies Against Unrelated Toxoid Vaccines After COVID-19: COVID-19 Infection Does Not Affect Toxoid Vaccine Antibody Levels.

Background: Lymphopenia is common in COVID-19. This has raised concerns that COVID-19 could affect the immune system akin to measles infection, which causes immune amnesia and a reduction in protective antibodies. Methods: We recruited COVID-19 patients (n = 59) in Helsinki, Finland, and collected plasma samples on 2 to 3 occasions during and after infection. We measured IgG antibodies to diphtheria toxin, tetanus toxoid, and pertussis toxin, along with total IgG, SARS-CoV-2 spike protein IgG, and neutralizing antibodies. We also surveyed the participants for up to 17 months for long-term impaired olfaction as a proxy for prolonged post-acute COVID-19 symptoms. Results: No significant differences were found in the unrelated vaccine responses while the serological response against COVID-19 was appropriate. During the acute phase of the disease, the SARSCoV-2 IgG levels were lower in outpatients when compared to inpatients. SARS-CoV-2 serology kinetics matched expectations. In the acute phase, anti-tetanus and anti-diphtheria IgG levels were lower in patients with prolonged impaired olfaction during follow up than in those without. Conclusions: We could not detect significant decline in overall humoral immunity during or after COVID-19 infection. In severe COVID-19, there appears to be a temporary decline in total IgG levels.

Survival and failure analysis of 167 medial opening wedge high tibial osteotomy with a locking titanium plate.

INTRODUCTION: This retrospective study investigated the survival rate and complications of medial opening wedge high tibial osteotomy (MOWHTO) with a precountered titanium locking plate. HYPOTHESIS: Advanced age (≥50years), gender, body mass index (BMI), type of osteotomy cut (monoplanar or biplanar), osteoarthritis (OA) grade, the use of bone grafting or substitution and preoperative hip-knee-ankle (HKA) have impact on MOWHTO survival. MATERIAL AND METHODS: A total of 167 knees (155 patients) were consecutively operated during the study period of 01.01.2006-31.12.2014. The primary outcome measure was survival without a need for revision to total knee arthroplasty (TKA). The secondary outcome was a major adverse event leading to revision surgery. Adverse events and complications were evaluated and radiological analyses were done. Furthermore, risk factors that affected the survival were analysed with the Cox regression model. RESULTS: The mean follow-up time was 7.7 (SD: 2.7, range: 0.9-14.5) years. The Kaplan-Meier estimates for the cumulative survival considering no need for TKA after MOWHTO was 90% at 5years, 78% at 10years and 61% at 14.5years (SE: 0.4, 95% CI: 11.2-12.9). The adverse event rate was 30% and 35% of the patients required a secondary surgery. The Cox regression model did not show that age, gender, weight, osteotomy type, the use of bone grafting or substitution, preoperative HKA angle or OA grade were not risk factors for conversion to arthroplasty. DISCUSSION: MOWHTO with locking plate provides good survival with no need for TKA in 78% of the knee medial OA patients at 10years of cumulative follow-up. However, a high adverse event rate (30%) is expected. Risk factors for conversion to TKA were not found and thereby hypothesis of this study was not proved. LEVEL OF EVIDENCE: VI; Retrospective cohort study.

Comparative analysis of COVID-19 vaccine responses and third booster dose-induced neutralizing antibodies against Delta and Omicron variants.

Two COVID-19 mRNA (of BNT162b2, mRNA-1273) and two adenovirus vector vaccines (ChAdOx1 and Janssen) are licensed in Europe, but optimization of regime and dosing is still ongoing. Here we show in health care workers (n = 328) that two doses of BNT162b2, mRNA-1273, or a combination of ChAdOx1 adenovirus vector and mRNA vaccines administrated with a long 12-week dose interval induce equally high levels of anti-SARS-CoV-2 spike antibodies and neutralizing antibodies against D614 and Delta variant. By contrast, two doses of BNT162b2 with a short 3-week interval induce 2-3-fold lower titers of neutralizing antibodies than those from the 12-week interval, yet a third BNT162b2 or mRNA-1273 booster dose increases the antibody levels 4-fold compared to the levels after the second dose, as well as induces neutralizing antibody against Omicron BA.1 variant. Our data thus indicates that a third COVID-19 mRNA vaccine may induce cross-protective neutralizing antibodies against multiple variants.

Anterior glenohumeral instability treated with arthroscopic Bankart operation - a retrospective 5-year follow-up study.

BACKGROUND: This retrospective study investigated 5-year results of primary arthroscopic operation for anterior glenohumeral instability (AI) with special interest in patients aged<25 years and gender. HYPOTHESIS: Recurrence of AI is higher in male patients aged<25 years than older patients or females. PATIENTS AND METHODS: Primary arthroscopic Bankart repair was performed between January 2009 and December 2015 on 156 shoulders [154 patients, 104/156 (67%) males]. The mean follow-up was 5.6 (SD 2.1, range 0.4-8.9) years. Outcome measures, including re-dislocation, fear of dislocation, Western Ontario instability index, Subjective shoulder value and pain Numerical rating scale scores, the number of revision surgeries and satisfaction with the result of surgical treatment, were assessed for 130 shoulders [82/130 (63%) males]. AI recurrence was defined as a dislocation or a fear of such. RESULTS: The Kaplan-Meier analysis estimates for the cumulative survival of stable shoulders were 28% at 8.8 years for patients aged<25 years (SE 0.4, CI 95% 5.5-7.2) and 53% at 8.9 years for patients aged ≥25 years (SE 0.2, CI 95% 7.2-8.0; p=0.005). The Kaplan-Meier estimates for the cumulative survival of stable shoulders were 50% at 8.9 years for males (SE 0.3, CI 95% 6.8-7.8) and 37% at 8.6 years for females (SE 0.3, CI 95% 6.5-7.7; p=0.8). Mean time to revision was 2.4 (SD 1.7, range 0.4-5.3) years. DISCUSSION: Recurrence of AI was higher in the patients aged<25 years (p=0.005), but gender was not a risk factor. Re-operation rate due to recurrent AI was 10% in this 5-year follow-up. LEVEL OF EVIDENCE: III; case-control study.