The incidence of congenital pseudarthrosis of the clavicle and review of the literature.

The aim of this study was to identify the hitherto unknown incidence of congenital pseudarthrosis of the clavicle (CPC), based on a cohort of continuous livebirths born in our hospital, to review the literature and investigate if there is evidence supporting the published association between left-sided CPC and dextrocardia. From our electronic medical record and radiology databases, we identified all live births and patients with the diagnosis of CPC born from 2000 to 2016. We reviewed the imaging which included one or both clavicles to search for unrecorded CPC cases and reviewed all retrievable CPC publications listed in PubMed and publications quoted within these publications going back to 1910. We identified 87 407 livebirths of which 41 800 had radiological studies done, 14 885 showing one or both clavicles. We found five cases of CPC, two from the electronic database and three from our imaging review, giving an incidence of 1 of 17 481 livebirths. We identified 138 publications reporting paediatric and adult CPC cases and 12 review articles, including 429 patients (187 female; 159 male; 83 unknown) with 456 CPCs and a minimum of 24 additional patients from case reports for which we could not retrieve details. Two publications reported one case of left-sided CPC with dextrocardia, either not showing left/right marking or only showing the CPC with the aortic knob on the same side. We report the first CPC incidence of 0.0057%, provide the by far most inclusive CPC epidemiology based on 429 patients and could not find reliable proof that there has ever been a patient with left-sided CPC which was associated with dextrocardia.

Five-year results after total knee arthroplasty in lymphoedema and lipoedema: encouraging functional and clinical outcomes and low rates of infection.

BACKGROUND: The aim of this study was to define outcomes after total knee arthroplasty (TKA) in lymphoedema and lipoedema patients managed by a multidisciplinary team and daily compression bandaging. METHODS: A retrospective study was performed in a single centre. Between 2007 and 2018, 36 TKA procedures were performed on 28 consecutive patients with a diagnosis of lymphoedema and lipoedema. Oxford Knee Scores (OKS), EuroQol-5D (EQ-5D) scores, satisfaction scores, radiographs, and complications were obtained at the final follow-up. Patients were admitted to the hospital up to two weeks prior to surgery and remained on the ward for daily compression bandaging by the specialist lymphoedema team. RESULTS: Over the study period, 36 TKAs were performed on 28 patients (5 males, 23 females) with a mean age of 71 years (range 54-90). Of these, 30 TKAs were in patients with lymphoedema, five with lipoedema, and one with a dual diagnosis. Overall, 28 TKAs (21 patients) were available at the final follow-up with a mean follow-up time of 61 months (range 9-138). The mean BMI was 38.5 kg/m2. The mean pre-operative and post-operative Oxford Knee Score increased from 18 (range 2-38) to 29 (range 10-54); p < 0.001. EQ-5D score increased from 0.48 (range 0.15-0.80) to 0.74 (0.34-1.00) (p < 0.001). Mean post-operative satisfaction was 7.6/10 (range 2-10), with 89.3% TKAs satisfied. Complications were one (4%, 1/28) deep vein thrombosis, one superficial wound infection, one prosthetic joint infection, one stiff knee requiring manipulation, and one intra-operative femoral fracture. CONCLUSIONS: Lymphoedema and lipoedema should not be seen as barriers to TKA if adopting a multidisciplinary approach.

Broadly neutralizing antibody responses in the longitudinal primary HIV-1 infection Short Pulse Anti-Retroviral Therapy at Seroconversion cohort.

OBJECTIVE: Development of immunogens that elicit an anti-HIV-1 broadly neutralizing antibody (bnAb) response will be a key step in the development of an effective HIV-1 vaccine. Although HIV-1 bnAb epitopes have been identified and mechanisms of action studied, current HIV-1 envelope-based immunogens do not elicit HIV-1 bnAbs in humans or animal models. A better understanding of how HIV-1 bnAbs arise during infection and the clinical factors associated with bnAb development may be critical for HIV-1 immunogen design efforts. DESIGN AND METHODS: Longitudinal plasma samples from the treatment-naive control arm of the Short Pulse Anti-Retroviral Therapy at Seroconversion (SPARTAC) primary HIV-1 infection cohort were used in an HIV-1 pseudotype neutralization assay to measure the neutralization breadth, potency and specificity of bnAb responses over time. RESULTS: In the SPARTAC cohort, development of plasma neutralization breadth and potency correlates with duration of HIV infection and high viral loads, and typically takes 3-4 years to arise. bnAb activity was mostly directed to one or two bnAb epitopes per donor and more than 60% of donors with the highest plasma neutralization having bnAbs targeted towards glycan-dependent epitopes. CONCLUSION: This study highlights the SPARTAC cohort as an important resource for more in-depth analysis of bnAb developmental pathways.

Cortical Strut Graft for Enigmatic Thigh Pain in Uncemented Total Hip Replacement.

Aims Enigmatic thigh pain in uncemented femoral components of a total hip replacement can be severe and disabling. Treatment can be conservative or surgical with cortical strut graft or revision of the femoral stem. Cortical strut grafting may offer good results with reduced morbidity. The aim of this study was to report the functional and radiographic outcomes of four patients with enigmatic thigh pain treated with cortical strut allograft. Materials and Methods Between 2016 and 2018, four women underwent cortical strut allografting at two centres. All patients had an uncemented, proximally porous S-ROM femoral implant (DePuy, Warsaw, In, USA). All other causes of anterolateral thigh pain were excluded. The mean age was 36.7 years (range: 29-51 years). Patients were followed up for a minimum of 14 months (range: 14-38 months). The University of California, Los Angles (UCLA) activity score, pain scores, complications, and radiographs at six weeks, three months, six months, nine months and one year were recorded. Results Mean UCLA activity scores increased from 3.2 (range: 2-4) to 6.2 (range: 6-7) post-operatively. Radiologically, all four patients had complete osseointegration of their strut grafts. Pain scores decreased at six weeks and at six months. One deep venous thrombosis occurred. One patient experienced recurrence of anterolateral thigh pain 26 months post-strut graft, which resolved with protected weight-bearing and analgesia for three months. Conclusions In uncemented femoral prostheses, cortical strut grafting to treat enigmatic thigh pain can reduce symptoms and increase activity without the need to revise a well-fixed femoral stem. We add to the growing body of evidence that this can be a successful surgical technique.

Serial C-reactive Protein Monitoring in Prosthetic Joint Infection: A Powerful Predictor or Potentially Pointless?

Background Serum C-reactive protein (CRP) is an important test in the initial diagnosis of prosthetic joint infection (PJI). There is no widely accepted algorithm for the resolution of PJI. Surgeons have traditionally used CRP to determine if the infection has resolved. However, this practice is not currently supported by significant data.  Methods A retrospective analysis of our departmental arthroplasty database was conducted to determine mean values of CRP pre and postoperatively for PJI treated with the debridement, antibiotics and implant retention (DAIR) procedure, single-stage revision and two-stage revision. Receiver operating characteristic (ROC) curves were calculated to determine the sensitivity and specificity of CRP testing in diagnosing persistent infection. Results Of the 121 patients who had undergone treatment (75 hip replacements and 48 knee replacements), there were 26 cases of persistent infection. There was no statistical significance in the mean CRP values between successful and unsuccessful treatment groups. The areas under ROCs (AUCs) for CRP values predicting outcomes ranged from 0.46 to 0.73. Conclusion Our study does not support the use of serial CRP monitoring as an indicator of the successful eradication of PJI.

The Pediatric Hip: A Rare Case of Acetabular Labral Tear and Paralabral Cyst: A Case Report.

CASE: We report the case of an active 8-year-old patient with a 2-year history of groin and thigh pain. Magnetic resonance imaging of the hip demonstrated a paralabral cyst arising from a superior labral tear. Arthroscopic labral repair and decompression of the cyst were performed, and the patient remains asymptomatic at 2-year follow-up. CONCLUSIONS: Acetabular labral tears with concomitant paralabral cysts have been described in the literature in the adult population and successfully treated arthroscopically. We propose that surgeons should be aware of this as a cause for undiagnosed groin and thigh pain in the pediatric population and that arthroscopic management is successful.

Increasing the CpG dinucleotide abundance in the HIV-1 genomic RNA inhibits viral replication.

BACKGROUND: The human immunodeficiency virus type 1 (HIV-1) structural protein Gag is necessary and sufficient to form viral particles. In addition to encoding the amino acid sequence for Gag, the underlying RNA sequence could encode cis-acting elements or nucleotide biases that are necessary for viral replication. Furthermore, RNA sequences that inhibit viral replication could be suppressed in gag. However, the functional relevance of RNA elements and nucleotide biases that promote or repress HIV-1 replication remain poorly understood. RESULTS: To characterize if the RNA sequence in gag controls HIV-1 replication, the matrix (MA) region was codon modified, allowing the RNA sequence to be altered without affecting the protein sequence. Codon modification of nucleotides (nt) 22-261 or 22-378 in gag inhibited viral replication by decreasing genomic RNA (gRNA) abundance, gRNA stability, Gag expression, virion production and infectivity. Comparing the effect of these point mutations to deletions of the same region revealed that the mutations inhibited infectious virus production while the deletions did not. This demonstrated that codon modification introduced inhibitory sequences. There is a much lower than expected frequency of CpG dinucleotides in HIV-1 and codon modification introduced a substantial increase in CpG abundance. To determine if they are necessary for inhibition of HIV-1 replication, codons introducing CpG dinucleotides were mutated back to the wild type codon, which restored efficient Gag expression and infectious virion production. To determine if they are sufficient to inhibit viral replication, CpG dinucleotides were inserted into gag in the absence of other changes. The increased CpG dinucleotide content decreased HIV-1 infectivity and viral replication. CONCLUSIONS: The HIV-1 RNA sequence contains low abundance of CpG dinucleotides. Increasing the abundance of CpG dinucleotides inhibits multiple steps of the viral life cycle, providing a functional explanation for why CpG dinucleotides are suppressed in HIV-1.

Unravelling the Molecular Basis of High Affinity Nanobodies against HIV p24: In Vitro Functional, Structural, and in Silico Insights.

Preventing the spread of infectious diseases remains an urgent priority worldwide, and this is driving the development of advanced nanotechnology to diagnose infections at the point of care. Herein, we report the creation of a library of novel nanobody capture ligands to detect p24, one of the earliest markers of HIV infection. We demonstrate that these nanobodies, one tenth the size of conventional antibodies, exhibit high sensitivity and broad specificity to global HIV-1 subtypes. Biophysical characterization indicates strong 690 pM binding constants and fast kinetic on-rates, 1 to 2 orders of magnitude better than monoclonal antibody comparators. A crystal structure of the lead nanobody and p24 was obtained and used alongside molecular dynamics simulations to elucidate the molecular basis of these enhanced performance characteristics. They indicate that binding occurs at C-terminal helices 10 and 11 of p24, a negatively charged region of p24 complemented by the positive surface of the nanobody binding interface involving CDR1, CDR2, and CDR3 loops. Our findings have broad implications on the design of novel antibodies and a wide range of advanced biomedical applications.