Basicervical femoral neck fractures: an observational study derived from the Swedish Fracture Register.

BACKGROUND AND PURPOSE: Limited research has been conducted on basicervical femoral neck fractures (bFNFs). The importance of displacement in clinical outcomes remains unclear. We aimed to characterize patient demographics, degree of displacement, treatment, treatment failures, and reoperations in a cohort of fractures from the Swedish Fracture Register (SFR). METHODS: 1,260 fractures in 1,185 individuals ≥ 60 years who had a bFNF registered in the SFR at 6 orthopedic departments from 2011 to 2020 were screened through radiographic review. The final sample included 291 patients with a confirmed bFNF. The medical records of these 291 patients were reviewed. We assessed baseline characteristics, initial fracture dislocation, treatment methods, tip-apex distance, failures, reoperations, and mortality. RESULTS: The mean age was 82 years (range 60-101, 55% women). 98 (34%) were undisplaced and 193 (66%) displaced. All patients underwent operative treatment. In the undisplaced group 95 (97%) patients received internal fixation (IF) and 3 (3%) had primary hip arthroplasty. In the displaced group 149 (77%) received IF and 41 (21%) had primary hip arthroplasty. 33 (11%) suffered treatment failure. When treating an undisplaced bFNF with IF, only 3 (3%) experienced treatment failure, in contrast to the 24 (16%) failure rate for a displaced bFNF. CONCLUSION: Undisplaced bFNFs have a low failure rate when treated with IF. For displaced bFNF treated with IF the failure rate is considerably higher. There is a need for further investigation of classification, treatment, and outcome of bFNF.

Analysis of fracture-related infections from Swedish insurance claims between 2011 and 2021.

Fracture-related infections (FRI) pose a serious complication with an incidence of 1-2%. This study aimed to analyze compensation claims submitted to The Swedish National Patient Insurance Company (LÖF) because of FRI after closed/open reduction and internal fixation (C/ORIF) in the four most common fracture sites (proximal humerus, distal radius, hip, ankle). Patients registered in the LÖF database with a suspected FRI between 2011 and 2021 were identified by matching International Classification of Diseases and procedural codes indicative of a combination of fractures to the proximal humerus, distal radius, hip and ankle, C/ORIF and infection. Medical records were reviewed for fracture sites, pathogens and complications. Data from the Swedish Fracture Register (SFR) were extracted to estimate the proportion of reported claims to the presumed number of FRI. Of 122 FRI identified in the LÖF database, 34 were after C/ORIF in the proximal humerus, 12 in the distal radius, 28 in the hip and 48 in the ankle. LÖF compensated 111 patients (91%). Median time from C/ORIF to an FRI was 3 weeks (interquartile range 2-6), and 95% of all FRI occurred within 1 year after C/ORIF. Staphylococcus aureus was the most common pathogen in patients with a distal radius, hip and ankle FRI. In contrast, Cutibacterium spp. were the most common aetiology in FRI of the proximal humerus. The total number of fractures treated with C/ORIF in the four fracture sites registered in the SFR during 2021 was 18,711. Most of the FRI patients were diagnosed within the first year after C/ORIF, and 91% of the patients received compensation. Given an expected FRI incidence of 1-2%, our estimates with extrapolated data from the SFR indicate that < 10% of affected patients applied for compensation.

Total Wrist Arthroplasty With a New Design, 20 Cases With 8-Year Follow-Up.

PURPOSE: Total wrist arthroplasty (TWA) is an established motion-preserving alternative to arthrodesis in the treatment of wrist arthritis, but post-TWA complications requiring additional surgery remain an issue. A new TWA design has been proposed. The purpose of this study was to report the outcome of a cohort study of 20 patients who underwent surgery using the new TWA design. METHODS: Patients were assessed before surgery and at 1, 2, and 8 years after surgery for visual analog scale (VAS) pain scores, wrist range of motion, hand grip strength, and patient-reported outcome measures (PROMs). Radiographic examination was conducted for evidence of prosthetic loosening. Reasons for revision were analyzed. RESULTS: In total, 24 reoperations were performed, including 12 revisions in 6 patients. Patient-reported outcome measures improved significantly at the 2-year follow-up compared with preoperative values. Hand grip strength, wrist extension, and VAS pain scores improved significantly at the 2-year follow-up. No radiographic loosening of the components was observed, but backing out of the carpal screws was noted in 16 of the 20 cases. CONCLUSIONS: The new TWA resulted in improved VAS pain scores, PROMs, wrist extension, and hand grip strength. The high frequency of reoperation is a concern, and modification of the implant is needed. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Preclinical development of a novel Group B Streptococcus (GBS) vaccine candidate for maternal immunization based upon the alpha-like protein family of GBS surface proteins (Alp).

A novel Group B Streptococcus (GBS) vaccine, based upon the GBS alpha-like surface proteins, is being developed by MinervaX for administration to pregnant women. The vaccine is intended to generate antibodies (IgG) capable of crossing the placenta, in order to passively immunize the baby and provide protection in utero and up to 3 months after birth. An initial vaccine candidate, GBS-NN (based on the N-terminal domains of Rib and AlphaC surface proteins) was replaced, due to insufficient cross-reactivity with the two other N-terminal proteins (Alp1 and Alp2/3), by a modified vaccine candidate designated GBS-NN/NN2 that included all four AlpNs. Preclinical studies raised no safety concerns and the subsequent Phase I clinical trial demonstrated that the vaccine was well tolerated and strongly immunogenic. As the vaccine is intended for use during pregnancy for maternal immunization, an embryofetal study in rats and a fertility and embryofetal study in rabbits were performed, in both cases using GBS-NN/NN2. Vaccination of female rats or rabbits did not adversely affect embryofetal development or survival in either species, or mating or fertility in rabbits. In both studies, the pregnant animals developed immune responses to GBS-NN and GBS-NN2 proteins and concentrations of antibodies to both fusion proteins were detected in the fetuses and in the amniotic fluid. Data generated during these reproductive studies indicated a suitable safety margin (approximately 40-fold clinical dose) considered appropriate to support a subsequent human trial of GBS-NN/NN2 administered in the second and third trimesters of pregnancy.

Safety and immunogenicity of the group B streptococcus vaccine AlpN in a placebo-controlled double-blind phase 1 trial.

Group B streptococcus (GBS) is a leading cause of life-threatening neonatal infections and subsets of adverse pregnancy outcomes. Essentially all GBS strains possess one allele of the alpha-like protein (Alp) family. A maternal GBS vaccine, consisting of the fused N-terminal domains of the Alps αC and Rib (GBS-NN), was recently demonstrated to be safe and immunogenic in healthy adult women. To enhance antibody responses to all clinically relevant Alps, a second-generation vaccine has been developed (AlpN), also containing the N-terminal domain of Alp1 and the one shared by Alp2 and Alp3. In this study, the safety and immunogenicity of AlpN is assessed in a randomized, double-blind, placebo-controlled, and parallel-group phase I study, involving 60 healthy non-pregnant women. AlpN is well tolerated and elicits similarly robust and persistent antibody responses against all four Alp-N-terminal domains, resulting in enhanced opsonophagocytic killing of all Alp serotypes covered by the vaccine.

Clinical, Radiographic, and Patient-Perceived Outcome After Radial Hemi-Wrist Arthroplasty With a New Implant: 20 Cases With 5-Year Follow-up.

BACKGROUND: Distal component loosening is a common mode of failure in total wrist arthroplasty (TWA). A radial hemi-wrist arthroplasty (RHWA) has the potential to avoid problems related to the distal component in TWA. The aim of this study is to investigate clinical outcomes following surgical treatment with a new RHWA design. METHODS: In this pilot study of 20 consecutive RHWAs, patients were assessed preoperatively and postoperatively for range of motion, grip strength, Visual Analog Scale (VAS) pain scores, and functional scoring using Patient-Rated Wrist Evaluation (PRWE), Disabilities of the Arm, Shoulder, and Hand (DASH), and Canadian Occupational Performance Measure. Radiographs were analyzed at 12 months and 5 years (mean, 5.1 years) postoperatively. RESULTS: A total of 46 secondary surgeries were undertaken in 16 wrists, including 7 revisions. Another 6 patients are waiting for revision to radiocarpal arthrodesis. In non-revised patients, the DASH and PRWE scores improved, and wrist range of motion remained largely unchanged except for wrist flexion, which decreased. The VAS pain score during activity was reduced, and hand grip strength remained largely unchanged. CONCLUSIONS: The new implant resulted in improved functional scoring and improved VAS pain scores in non-revised patients, but many cases needed secondary surgery due to persistent pain. The high revision rate is a major concern, and further use of the implant in its current form cannot be recommended.

Volar Locking Plate Compared With Combined Plating of AO Type C Distal Radius Fractures: A Randomized Controlled Study of 150 Cases.

PURPOSE: The optimal way to stabilize intra-articular distal radius fractures is unclear despite recent advances in surgical management. Volar plating is the most common treatment but may not be sufficient for more complex intra-articular AO type C fractures. The purpose of this randomized controlled study was to evaluate the radiographic and clinical outcomes following surgical treatment of AO type C distal radius fractures, comparing volar with combined plating. METHODS: In this study, 150 patients were randomized to volar locking plate (n = 75) or combined plating (n = 75) following a distal radius fracture AO type C. The 1-year follow-up included radiographic outcome (Batra score), visual analog scale pain score, hand grip strength, wrist range of motion, Patient-Rated Wrist Evaluation score, and Quick Disabilities of the Arm, Shoulder, and Hand score. RESULTS: Overall, 147 patients (median age 61 years) completed the 1-year follow-up (73 patients with volar plate and 74 with combined plating). No difference was found in radiographic outcome between the treatment groups. The volar plate group had significantly better Patient-Rated Wrist Evaluation scores, Quick Disabilities of the Arm, Shoulder, and Hand scores, hand grip strength, visual analog scale scores during activity, and flexion, extension, ulnar and radial deviation than the combined plate group. Hardware removal was performed in 10% in the volar plate group and in 31% in the combined plate group. There was no postoperative infection in the volar plate group but 3 cases in the combined plate group. CONCLUSIONS: In patients with complex AO type C intra-articular fractures, volar and combined plating yielded the same radiographic result. The differences in Patient-Rated Wrist Evaluation and Quick Disabilities of the Arm, Shoulder, and Hand scores between the groups did not reach the thresholds for minimal clinically important differences, suggesting similar clinical outcome. The combined plating group had a considerably higher frequency of hardware removal and postoperative infections. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic I.

A Recombinant Alpha-Like Protein Subunit Vaccine (GBS-NN) Provides Protection in Murine Models of Group B Streptococcus Infection.

BACKGROUND: Group B Streptococcus (GBS) transmission during pregnancy causes preterm labor, stillbirths, fetal injury, or neonatal infections. Rates of adult infections are also rising. The GBS-NN vaccine, engineered by fusing N-terminal domains of GBS Alpha C and Rib proteins, is safe in healthy, nonpregnant women, but further assessment is needed for use during pregnancy. Here, we tested GBS-NN vaccine efficacy using mouse models that recapitulate human GBS infection outcomes. METHODS: Following administration of GBS-NN vaccine or adjuvant, antibody profiles were compared by ELISA. Vaccine efficacy was examined by comparing infection outcomes in GBS-NN vaccinated versus adjuvant controls during systemic and pregnancy-associated infections, and during intranasal infection of neonatal mice following maternal vaccination. RESULTS: Vaccinated mice had higher GBS-NN-specific IgG titers versus controls. These antibodies bound alpha C and Rib on GBS clinical isolates. Fewer GBS were recovered from systemically challenged vaccinated mice versus controls. Although vaccination did not eliminate GBS during ascending infection in pregnancy, vaccinated dams experienced fewer in utero fetal deaths. Additionally, maternal vaccination prolonged neonatal survival following intranasal GBS challenge. CONCLUSIONS: These findings demonstrate GBS-NN vaccine efficacy in murine systemic and perinatal GBS infections and suggest that maternal vaccination facilitates the transfer of protective antibodies to neonates.

A group B Streptococcus alpha-like protein subunit vaccine induces functionally active antibodies in humans targeting homotypic and heterotypic strains.

Maternal vaccination is a promising strategy for preventing neonatal disease caused by group B Streptococcus. The safety and immunogenicity of the prototype vaccine GBS-NN, a fusion protein consisting of the N-terminal domains of the alpha-like proteins (Alp) αC and Rib, were recently evaluated favorably in healthy adult women in a phase 1 trial. Here we demonstrate robust immunoglobulin G (IgG) and immunoglobulin A (IgA) responses against αC and Rib, as well as against the heterotypic Alp family members Alp1-Alp3. IgA and heterotypic IgG responses are more variable between subjects and correlate with pre-existing immunity. Vaccine-induced IgG mediates opsonophagocytic killing and prevents bacterial invasion of epithelial cells. Like the vaccine-induced response, naturally acquired IgG against the vaccine domains is dominated by IgG1. Consistent with the high IgG1 cross-placental transfer rate, naturally acquired IgG against both domains reaches higher concentrations in neonatal than maternal blood, as assessed in a separate group of non-vaccinated pregnant women and their babies.

Posttraumatic Arthritis After Combined Plating of Distal Radius Fractures AO Type C: A 7-Year Follow-up of 97 Cases.

BACKGROUND: Volar locking plate fixation is the most common method of operative fixation of distal radius fractures (DRFs). For more complex cases, combined plating is an option for stabilizing intra-articular fragments. The prevalence of posttraumatic arthritis (PA) after an intra-articular DRF, and its relation to patient-reported outcome measures (PROMs), remains unclear. The purpose of this study was to study the prevalence of PA and its correlation to clinical outcome measures. METHODS: We evaluated 97 consecutive patients with intra-articular DRF, operated with combined plating, 7 years postoperatively. The primary outcome measure was the prevalence of radiographic PA. Secondary outcome measures included visual analog scale (VAS) pain score, hand grip strength, wrist range of motion (ROM), Patient-Rated Wrist Evaluation (PRWE) score, and Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) score. Radiographic examination was performed between 1 and 7 years postoperatively. RESULTS: The prevalence of PA was 29% at the 7-year follow-up. No correlation was found between PA and ROM, hand grip strength, PRWE, QuickDASH, VAS pain scores, or radiographic reduction. Median wrist ROM and grip strength were significantly inferior compared with the uninjured side. Hardware removal was performed in 51.5% of cases. There were 2 cases of tendon ruptures. CONCLUSIONS: Combined plating can yield a good clinical outcome 7 years postoperatively and a low prevalence of PA. The presence of PA did not correlate to clinical outcome measures or to the accuracy of anatomical reduction 1 year postoperatively. The frequency of tendon ruptures was acceptable, but the high frequency of hardware removal is a concern.

Safety and immunogenicity of a prototype recombinant alpha-like protein subunit vaccine (GBS-NN) against Group B Streptococcus in a randomised placebo-controlled double-blind phase 1 trial in healthy adult women.

BACKGROUND: Group B Streptococcus (GBS) is the leading cause of life-threatening infections in new-borns and may cause invasive disease, stillbirth and preterm delivery during pregnancy. While no licensed vaccine exists, maternal immunization might protect against neonatal disease and adverse pregnancy outcomes. We assessed the safety and immunogenicity of a prototype vaccine consisting of the fused N-terminal domains of the AlphaC and Rib surface proteins of GBS (GBS-NN). METHODS: GBS-NN was tested in a randomised, double-blind, placebo-controlled, parallel group, phase I study, in healthy non-pregnant women. A dose-escalation phase, with two doses, four weeks apart, of 10, 50 or 250 µg, administered with or without aluminium hydroxide, was initially assessed (n = 60). This was followed by a dose-confirmation study, where one dose of 100 µg adjuvanted GBS-NN was compared with two doses of either 50 or 100 µg adjuvanted GBS-NN, again administered with four weeks interval between the doses (n = 180). Safety and immunogenicity were monitored for one year. RESULTS: GBS-NN was well tolerated with some, mostly mild, injection site reactions observed. Adjuvant significantly increased antibody concentrations and the response was boosted by a second dose. The IgG GMCs remained strongly elevated during the whole one-year duration of the study. Maximal responses occurred after two 50 µg doses, resulting in IgG GMC of 16.9 µg/ml at the primary immunological endpoint, twelve weeks after the first dose. For this regimen, 100% and 89% of the subjects achieved antibody levels above the arbitrary thresholds of 1 and 4 µg/ml, respectively. The added beneficial effect of a second dose was most pronounced for subjects with pre-existing IgG levels below the median of the entire cohort. CONCLUSION: The prototype GBS-NN vaccine was found to be well tolerated and highly immunogenic with an optimal regimen of two doses of 50 µg in the presence of adjuvant. Further development of a maternal vaccine based on the N-terminal domains of the alpha-like protein family of GBS is warranted (NCT02459262).

Total Wrist Arthroplasty: A 10-Year Follow-Up.

PURPOSE: To assess long-term implant survival in total wrist arthroplasty (TWA), comparing 4 different implants. METHODS: In a prospective cohort of 124 patients, 136 TWAs were evaluated 5 years and 10 years after surgery. The TWAs were implanted between 2005 and 2009. The primary outcome was implant survival. Survival analysis was performed with revision and radiographic loosening as the final end point. Revision was defined as exchange of whole or parts of the prosthesis. Implant loosening was assessed using radiographic examination at the 5-year and 10-year follow-up. Secondary outcome measures included wrist range of motion, hand grip strength, visual analog scale (VAS) pain scores, and patient-related outcome measures, including Disabilities of the Arm, Shoulder, and Hand (DASH), Patient-Rated Wrist Evaluation (PRWE), and Canadian Occupational Performance Measure (COPM). RESULTS: Total cumulative implant survival was 92% with revision as the primary end point. When including a nonrevised radiographic loose implant as a failure, total implant survival was 75%. Radiographic loosening differed significantly between the implants with a range in frequency from 0% to 37.5%. At the 10-year follow-up, assessing the nonrevised TWAs, range of motion was preserved compared with preoperative values. Significant improvement was recorded for hand grip strength, VAS pain scores, and patient-related outcome measures at the 10-year follow-up compared with preovperative values. CONCLUSIONS: High 10-year implant survival was found when defining the primary end point as revision of any cause. When including radiographic loosening of the implant in the survival analysis, implant survival was considerably lower. However, radiographic loosening does not seem to correlate with changes in secondary outcome measures, questioning the need for revision surgery in these cases. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Serocorrelates of protection against infant group B streptococcus disease.

Group B streptococcus (GBS) is a leading cause of young infant mortality and morbidity globally, with vaccines being developed for over four decades but none licensed to date. A serocorrelate of protection against invasive disease in young infants is being considered to facilitate vaccine early licensure, followed by demonstration of efficacy assessed postlicensure. In this Review, we synthesise the available scientific evidence to define an immune correlate associated with GBS disease risk reduction on the basis of studies of natural infection. We summarise studies that have investigated GBS serum anticapsular or anti-protein antibodies, and studies measuring the association between antibody function and disease risk reduction. We highlight how knowledge on the development of correlates of protection from existing vaccines could be harnessed to facilitate GBS vaccine development. These lessons include aggregation of serocorrelates of protection for individual serotypes, understanding the relationship between immunity derived from natural exposure of adults and vaccine-induced immunity, or using extrapolation of protection from in-vitro immunoassay results. We also highlight key considerations for the assessment of the role of antibodies to derive a serocorrelate of risk reduction in future seroepidemiological studies of GBS disease.

Temperature-Induced Self-Assembly of the Group B Streptococcus (GBS) Fusion Antigen GBS-NN.

Group B Streptococcus (GBS) is a leading cause of serious bacterial neonatal infections worldwide, which provides an unmet medical need for a globally effective vaccine. The recombinant GBS fusion antigen GBS-NN contains the N-terminal regions of the GBS Rib and Alpha C proteins. It shows promising immunogenicity eliciting protective immunity in mice and encouraging results in early human clinical trials. Understanding the physical stability of GBS-NN containing conformational B-cell epitopes is crucial to ensure optimal vaccine stability, efficacy, and safety. We initially discovered that GBS-NN is prone to form higher-order structures at elevated temperatures. We therefore investigated the self-assembly behavior of GBS-NN and characterized the higher-order conformational structures as a function of temperature. In the native state, GBS-NN exists as a monomer and has a secondary structure containing α-helix and ß-sheet. Langmuir studies demonstrated that the native protein is highly surface-active and forms a monolayer film at the air-water interface because of its amphipathic properties. The conformational stability of GBS-NN was measured as a function of temperature. GBS-NN has an unusual thermal behavior with a phase transition of approximately 61 °C, which is not accompanied by any major changes in the secondary structure. However, the antigen showed irreversible self-assembly as a function of temperature into higher-order structures with a hydrodynamic diameter of approximately 100 nm. Cryo-transmission electron microscopy analyses demonstrated that these self-assemblies consist of vesicular, ring-like structures with a hollow aqueous interior. Therefore, GBS-NN is a physically stable monomeric protein but is prone to temperature-induced self-assembly above 61 °C.

Revision Arthroplasty of the Wrist in Patients With Rheumatoid Arthritis, Mean Follow-Up 6.6 Years.

PURPOSE: Management of failed total wrist arthroplasty (TWA) can be challenging; surgical treatment options include salvage arthrodesis, revision arthroplasty, and resection arthroplasty. There are few studies regarding salvage arthrodesis, and revision arthroplasty has been infrequently investigated. The aim of the study was to report the outcome after revision arthroplasty of the wrist. METHODS: A retrospective cohort of 16 revision TWAs was evaluated between 2003 and 2016. Data were collected before surgery and 1 and 5 years after surgery. The indication for revision arthroplasty was failed TWA. The primary end point was implant survival. Secondary outcome measures included visual analog scale (VAS) pain scores, range of motion, handgrip strength, and functional scoring with the Canadian Occupational Performance Measure (COPM), Patient-Rated Wrist Evaluation (PRWE), and Disabilities of the Arm, Shoulder, and Hand (DASH). RESULTS: Mean follow-up was 6.6 years. Synthetic bone graft was used in 9 cases, allograft corticocancellous bone graft in 1 case, and cement in 6 cases. Of the 16 revision TWAs, 4 were re-revised, 1 because of infection, and 3 cases underwent total wrist arthrodesis. In the non-re-revised cases, range of motion and grip strength was preserved compared with preoperative results. The VAS pain score in activity improved, but not significantly, at 1 (median, 1; range, 0-4.5) and 5 years after surgery (median, 0) compared with before surgery (median, 5). The COPM performance and satisfaction as well as PRWE scores improved significantly at 1 year (median COPM performance, 4.8; COPM satisfaction, 5.6; and PRWE, 24) and improved, but not significantly, at the 5-year follow (median COPM performance, 4.8; COPM satisfaction, 5.0; and PRWE, 37) in the non-re-revised cases. CONCLUSIONS: Revision arthroplasty of the wrist is a valid motion-preserving option to wrist arthrodesis in the management of failed TWA. However, the outcome is uncertain and as many as 25% require additional surgery. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.