Amanatullah, Derek F.

Increasing rates of infection by antibiotic resistant bacteria have led to a resurgence of interest in bacteriophage (phage) therapy. Several phage therapy studies in animals and humans have been completed over the last two decades. We conducted a systematic review of safety and toxicity data associated with phage therapy in both animals and humans reported in English language publications from 2008–2021. Overall, 69 publications met our eligibility criteria including 20 animal studies, 35 clinical case reports or case series, and 14 clinical trials. After summarizing safety and toxicity data from these publications, we discuss potential approaches to optimize safety and toxicity monitoring with the therapeutic use of phage moving forward. In our systematic review of the literature, we found some adverse events associated with phage therapy, but serious events were extremely rare. Comprehensive and standardized reporting of potential toxicities associated with phage therapy has generally been lacking in the published literature. Structured safety and tolerability endpoints are necessary when phages are administered as anti-infective therapeutics.

Aims The aim of this study was to assess the efficacy of non-selective and selective non-steroidal anti-inflammatory drugs (NSAIDs) in preventing heterotopic ossification (HO) after total hip arthroplasty (THA). Methods A thorough and systematic literature search was conducted and 29 studies were found that met inclusion criteria. Data were extracted and statistical analysis was carried out generating forest plots. Results Non-selective NSAIDs showed a significant decrease in the odds for forming HO after THA (odds ratio (OR) -1.35, confidence interval (CI) -1.83 to -0.86) when compared with placebo. Selective NSAIDs also showed a significant decrease in the odds for forming HO after THA when compared with placebo (OR -1.58, CI -2.41 to -0.75). When comparing non-selective NSAIDs with selective NSAIDs, there was no significant change in the odds for forming HO after THA (OR 0.22, CI -0.36 to 0.79). Conclusion Our meta-analyses of all available data suggest that both non-selective and selective NSAIDs are effective HO prophylaxis and can be used routinely after THA for pain control as well as prevention of HO. Indomethacin may serve as the benchmark among non-selective NSAIDs and celecoxib among selective NSAIDs. There was no difference in the incidence of HO between non-selective and selective NSAIDs, allowing physicians to choose either based on the clinical scenario and patient-specific factors. Cite this article: Bone Joint J 2018;100-B:915–22.

AimsWe wished to quantify the extent of soft-tissue damage sustained during minimally invasive total hip arthroplasty through the direct anterior (DA) and direct superior (DS) approaches.Materials and MethodsIn eight cadavers, the DA approach was performed on one side, and the DS approach on the other, a single brand of uncemented hip prosthesis was implanted by two surgeons, considered expert in their surgical approaches. Subsequent reflection of the gluteus maximus allowed the extent of muscle and tendon damage to be measured and the percentage damage to each anatomical structure to be calculated.ResultsThe DA approach caused substantially greater damage to the gluteus minimus muscle and tendon when compared with the DS approach (t-test, p = 0.049 and 0.003, respectively). The tensor fascia lata and rectus femoris muscles were damaged only in the DA approach. There was no difference in the amount of damage to the gluteus medius muscle and tendon, piriformis tendon, obturator internus tendon, obturator externus tendon or quadratus femoris muscle between approaches. The posterior soft-tissue releases of the DA approach damaged the gluteus minimus muscle and tendon, piriformis tendon and obturator internus tendon.ConclusionThe DS approach caused less soft-tissue damage than the DA approach. However the clinical relevance is unknown. Further clinical outcome studies, radiographic evaluation of component position, gait analyses and serum biomarker levels are necessary to evaluate and corroborate the safety and efficacy of the DS approach. Cite this article: Bone Joint J 2016;98-B1036–42.

When fracture of an extensively porous-coated femoral component occurs, its removal at revision total hip arthroplasty (THA) may require a femoral osteotomy and the use of a trephine. The remaining cortical bone after using the trephine may develop thermally induced necrosis. A retrospective review identified 11 fractured, well-fixed, uncemented, extensively porous-coated femoral components requiring removal using a trephine with a minimum of two years of follow-up.The mean time to failure was 4.6 years (1.7 to 9.1, standard deviation (sd) 2.3). These were revised using a larger extensively porous coated component, fluted tapered modular component, a proximally coated modular component, or a proximal femoral replacement. The mean clinical follow-up after revision THA was 4.9 years (2 to 22, sd 3.1). The mean diameter of the femoral component increased from 12.7 mm (sd 1.9) to 16.2 mm (sd 3.4; p > 0.001). Two revision components had radiographic evidence of subsidence that remained radiographically stable at final follow-up. The most common post-operative complication was instability affecting six patients (54.5%) on at least one occasion.A total of four patients (36.4%) required further revision: three for instability and one for fracture of the revision component. There was no statistically significant difference in the mean Harris hip score before implant fracture (82.4; sd 18.3) and after trephine removal and revision THA (81.2; sd 14.8, p = 0.918).These findings suggest that removal of a fractured, well-fixed, uncemented, extensively porous-coated femoral component using a trephine does not compromise subsequent fixation at revision THA and the patient’s pre-operative level of function can be restored. However, the loss of proximal bone stock before revision may be associated with a high rate of dislocation post-operatively.Cite this article: Bone Joint J 2015;97-B:1192–6.

Revision total hip arthroplasty (THA) is challenging when there is severe loss of bone in the proximal femur. The purpose of this study was to evaluate the clinical and radiographic outcomes of revision THA in patients with severe proximal femoral bone loss treated with a fluted, tapered, modular femoral component. Between January 1998 and December 2004, 92 revision THAs were performed in 92 patients using a single fluted, tapered, modular femoral stem design. Pre-operative diagnoses included aseptic loosening, infection and peri-prosthetic fracture. Bone loss was categorised pre-operatively as Paprosky types III-IV, or Vancouver B3 in patients with a peri-prosthetic fracture. The mean clinical follow-up was 6.4 years (2 to 12). A total of 47 patients had peri-operative complications, 27 of whom required further surgery. However, most of these further operations involved retention of a well-fixed femoral stem, and 88/92 femoral components (97%) remained in situ. Of the four components requiring revision, three were revised for infection and were well fixed at the time of revision; only one (1%) was revised for aseptic loosening. The most common complications were post-operative instability (17 hips, 19%) and intra-operative femoral fracture during insertion of the stem (11 hips, 12%). Diaphyseal stress shielding was noted in 20 hips (22%). There were no fractures of the femoral component. At the final follow-up 78% of patients had minimal or no pain.Revision THA in patients with extensive proximal femoral bone loss using the Link MP fluted, tapered, modular stem led to a high rate of osseointegration of the stem at mid-term follow-up.Cite this article: Bone Joint J 2015; 97-B:312–17.

Dysplasia of the hip, hypotonia, osteopenia, ligamentous laxity, and mental retardation increase the complexity of performing and managing patients with Down syndrome who require total hip replacement (THR). We identified 14 patients (six males, eight females, 21 hips) with Down syndrome and degenerative disease of the hip who underwent THR, with a minimum follow-up of two years from 1969 to 2009. In seven patients, bilateral THRs were performed while the rest had unilateral THRs. The mean clinical follow-up was 5.8 years (standard deviation (sd) 4.7; 2 to 17). The mean Harris hip score was 37.9 points (sd 7.8) pre-operatively and increased to 89.2 (sd 12.3) at final follow-up (p = 1x10-9). No patient suffered a post-operative dislocation. In three patients, four hips had revision THR for aseptic loosening at a mean follow-up of 7.7 years (sd 6.3; 3 to 17). This rate of revision THR was higher than expected. Our patients with Down syndrome benefitted clinically from THR at mid-term follow-up. Cite this article: Bone Joint J 2014;96-B:1455–8.