No clinical advantage with customized individually made implants over conventional off-the-shelf implants in total knee arthroplasty: a systematic review and meta-analysis.

INTRODUCTION: Total knee arthroplasty (TKA) can be performed with either conventional off-the-shelf (OTS) or customized individually-made (CIM) implants. The evidence for CIM implants is limited and variable, and the aim of this review was to compare clinical and radiological outcomes between CIM and OTS implants. METHODS: A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines. Studies reporting on clinical, radiological, or alignment outcomes for CIM and OTS implants were selected. The studies were appraised using the Methodical index for non-randomized studies tool. RESULTS: Twenty-three studies fulfilled the inclusion criteria. The studies comprised 2856 CIM and 1877 OTS TKAs. Revision rate was higher with CIM (5.9%) compared to OTS (3.7%) implants [OR 1.23(95% CI 0.69-2.18)]. Manipulation under anesthesia (MUA) was higher in CIM (2.2%) compared to OTS (1.1%) group [OR 2.95(95% CI 0.95-9.13)] and complications rate was higher in CIM (5%) vs. OTS (4.5%) [OR 1.45(95% CI 0.53-3.96)] but neither reached statistical significance. Length of stay was significantly shorter in CIM group 2.9 days vs. 3.5 days [MD - 0.51(95% CI - 0.82 to - 0.20)]. Knee Society Score showed no difference between CIM and OTS groups for Knee 90.5 vs. 90.6 [MD - 0.27(95% CI - 4.27 to 3.73)] and Function 86.1 vs. 83.1 [MD 1.51(95% CI - 3.69 to 6.70)]. CONCLUSION: CIM implants in TKA have theoretical benefits over OTS prostheses. However, in this present review, CIM implants were associated with higher revisions, MUA, and overall complication rates. There was no difference in outcome score and CIM implants did not improve overall target alignment; however, more CIM TKAs were found to be in the HKA target zone compared to OTS TKAs. The findings of this review do not support the general utilization of CIM over OTS implants in TKA.

Open and arthroscopic posterior bone block with iliac crest autograft for posterior shoulder instability - systematic review of clinical and radiological outcomes.

INTRODUCTION: Posterior shoulder instability (PSI) is a rare and challenging pathology to manage. The aim of this review was to assess and compare whether open and arthroscopic iliac crest bone graft (ICBG) bone block procedures succeeded in improving functional and clinical outcomes as well as radiological outcomes of union and graft resorption. HYPOTHESIS: We hypothesised that there will be no difference in recurrence rate and functional outcome between open and arthroscopic procedures but there will be a higher complication rate with open bone block procedures. METHODS: A systematic review was conducted in accordance with PRISMA guidelines using the online databases MEDLINE and Embase. The review was registered on the PROSPERO database. Studies of open or arthroscopic ICBG bone block procedures reporting patient reported outcome measures, recurrence, complications and progression to osteoarthritis and radiological outcomes of graft union and resorption were selected. Studies were appraised using the Methodical index for non-randomised studies (MINORS) tool. RESULTS: 14 studies satisfied the inclusion criteria; five studies were arthroscopic and nine used open techniques. A total of 183 patients and 201 shoulders were included, mean age was 25 years range (14-75 years). Recurrent instability ranged from 0% to 12.5% for arthroscopic and 0% to 36.4% for open studies. Arthroscopic studies had statistically significant increases in numerous functional outcome scores but there was no evidence for similar improvements in open studies. Osteoarthritis at follow-up ranged from 12.5% to 47% in arthroscopic and 0% to 81.8% for open studies. Arthroscopic complication rate ranged from 6.7% to 75% compared to 0% to 80% for open studies. Majority of complications were metalware related requiring surgical intervention. Partial graft resorption ranged from 7.7-100% after arthroscopic and 4.8-100% after open procedures. High union rates were seen with both open and arthroscopic techniques. CONCLUSION: This study highlights a lack of high-level evidence for arthroscopic and open posterior bone block procedures using ICBG to manage PSI. Functional and instability outcome scores showed significant improvement with arthroscopic ICBG bone block procedures however limited evidence was available for open studies. Metalwork related complications requiring revision and radiographic progression to osteoarthritis was high in both arthroscopic and open studies. LEVEL OF EVIDENCE: IV, systematic review.

Tumor Infiltrating Lymphocytes Target HLA-I Phosphopeptides Derived From Cancer Signaling in Colorectal Cancer.

There is a pressing need for novel immunotherapeutic targets in colorectal cancer (CRC). Cytotoxic T cell infiltration is well established as a key prognostic indicator in CRC, and it is known that these tumor infiltrating lymphocytes (TILs) target and kill tumor cells. However, the specific antigens that drive these CD8+ T cell responses have not been well characterized. Recently, phosphopeptides have emerged as strong candidates for tumor-specific antigens, as dysregulated signaling in cancer leads to increased and aberrant protein phosphorylation. Here, we identify 120 HLA-I phosphopeptides from primary CRC tumors, CRC liver metastases and CRC cell lines using mass spectrometry and assess the tumor-resident immunity against these posttranslationally modified tumor antigens. Several CRC tumor-specific phosphopeptides were presented by multiple patients' tumors in our cohort (21% to 40%), and many have previously been identified on other malignancies (58% of HLA-A*02 CRC phosphopeptides). These shared antigens derived from mitogenic signaling pathways, including p53, Wnt and MAPK, and are therefore markers of malignancy. The identification of public tumor antigens will allow for the development of broadly applicable targeted therapeutics. Through analysis of TIL cytokine responses to these phosphopeptides, we have established that they are already playing a key role in tumor-resident immunity. Multifunctional CD8+ TILs from primary and metastatic tumors recognized the HLA-I phosphopeptides presented by their originating tumor. Furthermore, TILs taken from other CRC patients' tumors targeted two of these phosphopeptides. In another cohort of CRC patients, the same HLA-I phosphopeptides induced higher peripheral T cell responses than they did in healthy donors, suggesting that these immune responses are specifically activated in CRC patients. Collectively, these results establish HLA-I phosphopeptides as targets of the tumor-resident immunity in CRC, and highlight their potential as candidates for future immunotherapeutic strategies.