Difference in Pain, Complication Rates, and Clinical Outcomes After Suprapatellar Versus Infrapatellar Nailing for Tibia Fractures?:A Systematic Review of 1447 Patients

OBJECTIVES: To assess the effectiveness of suprapatellar (SP)-nailing versus infrapatellar (IP)-nailing of tibia fractures in anterior knee pain, complications (retropatellar chondropathy, infection, and malalignment) and physical functioning and quality of life. A clinical question-driven and thorough systematic review of current literature is provided. DATA SOURCE: PubMed and Embase databases were searched for studies published between 2010 and 2020 relating to SP and IP-nailing of tibia fractures. The study is performed in concordance with PRISMA-guidelines. STUDY SELECTION: Studies eligible for inclusion were randomized controlled trials, prospective and retrospective observational studies reporting on outcomes of interest. DATA EXTRACTION: Data extraction was performed independently by 2 assessors. Methodological quality and risk of bias was assessed according to the guidelines of the McMaster Critical Appraisal. DATA SYNTHESIS: Continuous variables are presented as means with SD and dichotomous variables as frequency and percentages. The weighted mean, standardized weighted mean differences, and 95% confidence interval were calculated. A pooled analysis could not be performed because of differences in outcome measures, time-points, and heterogeneity. RESULTS: Fourteen studies with 1447 patients were analyzed. The weighted incidence of anterior knee pain was 29% after SP-nailing and 39% after IP-nailing, without reported significance. There was a significant lower rate of malalignment after the SP-approach (4% vs. 26%) with small absolute differences in all planes. No substantial differences were observed in retropatellar chondropathy, infection, physical functioning, and quality of life. CONCLUSIONS: This systematic review does not reveal superiority of either technique in any of the respective outcomes of interest. Definitive choice should depend on the surgeon's experience and available resources. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence

Dissemination of extensively drug-resistant NDM-producing Providencia stuartii in Europe linked to patients transferred from Ukraine, March 2022 to March 2023

BackgroundThe war in Ukraine led to migration of Ukrainian people. Early 2022, several European national surveillance systems detected multidrug-resistant (MDR) bacteria related to Ukrainian patients.AimTo investigate the genomic epidemiology of New Delhi metallo-β-lactamase (NDM)-producing Providencia stuartii from Ukrainian patients among European countries.MethodsWhole-genome sequencing of 66 isolates sampled in 2022-2023 in 10 European countries enabled whole-genome multilocus sequence typing (wgMLST), identification of resistance genes, replicons, and plasmid reconstructions. Five blaNDM-1-carrying-P. stuartii isolates underwent antimicrobial susceptibility testing (AST). Transferability to Escherichia coli of a blaNDM-1-carrying plasmid from a patient strain was assessed. Epidemiological characteristics of patients with NDM-producing P. stuartii were gathered by questionnaire.ResultswgMLST of the 66 isolates revealed two genetic clusters unrelated to Ukraine and three linked to Ukrainian patients. Of these three, two comprised blaNDM-1-carrying-P. stuartii and the third blaNDM-5-carrying-P. stuartii. The blaNDM-1 clusters (PstCluster-001, n = 22 isolates; PstCluster-002, n = 8 isolates) comprised strains from seven and four countries, respectively. The blaNDM-5 cluster (PstCluster-003) included 13 isolates from six countries. PstCluster-001 and PstCluster-002 isolates carried an MDR plasmid harbouring blaNDM-1,blaOXA-10, blaCMY-16, rmtC and armA, which was transferrable in vitro and, for some Ukrainian patients, shared by other Enterobacterales. AST revealed PstCluster-001 isolates to be extensively drug-resistant (XDR), but susceptible to cefiderocol and aztreonam-avibactam. Patients with data on age (n = 41) were 19-74 years old; of 49 with information on sex, 38 were male.ConclusionXDR P. stuartii were introduced into European countries, requiring increased awareness and precautions when treating patients from conflict-affected areas.</p

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Factors associated with subsequent surgical procedures after intramedullary nailing for tibial shaft fractures

Introduction: The reported rate of subsequent surgery after intramedullary nailing (IMN) of tibial shaft fractures (TSFs) is as high as 21%. However, most studies have not included the removal of symptomatic implant in these rates. The purpose of this study was to evaluate the subsequent surgery rate after IMN of TSFs, including the removal of symptomatic implants. Secondly, this study aimed to assess what factors are associated with subsequent surgery (1) to promote fracture and wound healing and (2) for the removal of symptomatic implants. Methods: One-hundred and ninety-one patients treated with IMN for TSFs were retrospectively included. The rate of subsequent surgery was determined. Bi- and multivariable analysis was used to identify variables associated with subsequent surgery. Results: Approximately half of patients (46%) underwent at least one subsequent surgical procedure. Forty-eight (25%) underwent a subsequent surgical procedure to promote fracture or wound healing. Age (P < 0.01), multi-trauma (P < 0.01), open fracture (P < 0.001) and index surgery during weekdays (P < 0.05) were associated with these procedures. Thirty-nine patients (20%) underwent a subsequent surgical procedure for removal of symptomatic implants. There was a significantly lower rate of implant removal in ASA II (11%) and ASA III–IV (14%) patients compared to ASA I patients (29%) (P < 0.05). Conclusions: Patients treated with IMN for TSFs should be consented that about one-in-two patients will undergo an additional surgical procedure. Half of these procedures are required to promote wound or fracture healing; the other half are for symptomatic implant removal. Level of evidence: Therapeutic level-IV

Prevalence of Rotational Malalignment After Intramedullary Nailing of Tibial Shaft Fractures: Can We Reliably Use the Contralateral Uninjured Side as the Reference Standard?

BACKGROUND: Intramedullary (IM) nailing is the treatment of choice for most tibial shaft fractures. However, an iatrogenic pitfall may be rotational malalignment. The aims of this retrospective analysis were to determine (1) the prevalence of rotational malalignment using postoperative computed tomography (CT) as the reference standard; (2) the average baseline tibial torsion of uninjured limbs; and (3) based on that normal torsion, whether the contralateral, uninjured limb can be reliably used as the reference standard. METHODS: The study included 154 patients (71% male and 29% female) with a median age of 37 years. All patients were treated for a unilateral tibial shaft fracture with an IM nail and underwent low-dose bilateral postoperative CT to assess rotational malalignment. RESULTS: More than one-third of the patients (n = 55; 36%) had postoperative rotational malalignment of ≥10°. Right-sided tibial shaft fractures were significantly more likely to display external rotational malalignment whereas left-sided fractures were predisposed to internal rotational malalignment. The uninjured right tibiae were an average of 4° more externally rotated than the left (mean rotation and standard deviation, 41.1° ± 8.0° [right] versus 37.0° ± 8.2° [left]; p < 0.01). Applying this 4° correction to our cohort not only reduced the prevalence of rotational malalignment (n = 45; 29%), it also equalized the distribution of internal and external rotational malalignment between the left and right tibiae. CONCLUSIONS: This study confirms a high prevalence of rotational malalignment following IM nailing of tibial shaft fractures (36%). There was a preexisting 4° left-right difference in tibial torsion, which sheds a different light on previous studies and current clinical practice and could have important implications for the diagnosis and management of tibial rotational malalignment. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence

Radial nerve palsy associated with closed humeral shaft fractures: a systematic review of 1758 patients

Background and purpose: Humeral shaft fractures are often associated with radial nerve palsy (RNP) (8–16%). The primary aim of this systematic review was to assess the incidence of primary and secondary RNP in closed humeral shaft fractures. The secondary aim was to compare the recovery rate of primary RNP and the incidence of secondary RNP between operative and non-operative treatment. Methods: A systematic literature search was performed in ‘Trip Database’, ‘Embase’ and ‘PubMed’ to identify original studies reporting on RNP in closed humeral shaft fractures. The Coleman Methodology Score was used to grade the quality of the studies. The incidence and recovery of RNP, fracture characteristics and treatment characteristics were extracted. Chi-square and Fisher exact tests were used to compare operative versus non-operative treatment. Results: Forty studies reporting on 1758 patients with closed humeral shaft fractures were included. The incidence of primary RNP was 10%. There was no difference in the recovery rate of primary RNP when comparing operative treatment with radial nerve exploration (98%) versus non-operative treatment (91%) (p = 0.29). The incidence of secondary RNP after operative and non-operative treatment was 4% and 0.4%, respectively (p 90% recovers without the need of (re-)intervention. No beneficial effect of early exploration on the recovery of primary RNP could be demonstrated when comparing patients managed non-operatively with those explored early. Patients managed operatively for closed humeral shaft fractures have a higher risk of developing secondary RNP. Level of evidence: Level IV; Systematic Review

Incidence, Predictors, and Fracture Mapping of (Occult) Posterior Malleolar Fractures Associated With Tibial Shaft Fractures

OBJECTIVES: To (1) evaluate the incidence of posterior malleolar fractures (PMFs) in patients with tibial shaft fractures (TSFs) using advanced imaging; (2) identify predictors for patients at risk of an (occult) PMF; and (3) describe PMF characteristics to guide "malleolus-first" fixation. DESIGN: Retrospective diagnostic imaging study. SETTING: Level-I trauma center. PATIENTS: One hundred sixty-four patients treated with intramedullary nailing for TSFs who underwent low-dose postoperative computed tomography (CT) scans to assess (mal)rotational alignment. INTERVENTION: Analysis of advanced imaging for the presence of PMFs. Univariate and multivariate analyses to identify predictors. Qualitative analysis of PMFs by fracture mapping. MAIN OUTCOME MEASURES: (1) Incidence of PMFs in patients with TSFs as diagnosed on post-op CT scans; (2) independent predictors for the presence of PMFs; and (3) PMF patterns. RESULTS: One in five patients with a TSF has an associated PMF (22%), increasing to one-in-two in patients with simple spiral fractures (56%). In 25% of patients, these fractures were occult. Univariate analysis identified simple spiral and distal third TSFs, proximal third and spiral fibula fractures, and low-energy trauma as predictors for PMFs. Multivariate analysis demonstrated that distal third and simple spiral TSFs were the only independent predictors. Haraguchi type I is the pattern specific to PMFs associated with TSF. CONCLUSIONS: Half of patients presenting with a simple spiral TSF have an associated PMF. In one in four patients, these are occult. Additional preoperative CT scan imaging may be considered in patients presenting with simple spiral distal third TSFs, despite negative lateral radiographs, so that PMFs can be identified and managed with "malleolus-first" fixation. LEVEL OF EVIDENCE: Diagnostic Level IV. See Instructions for Authors for a complete description of levels of evidence

Complications and subsequent surgery after intra-medullary nailing for tibial shaft fractures: Review of 8110 patients

Background: Intramedullary nailing of tibial shaft fractures has been common practice for decades. Nevertheless, complications occur frequently, and subsequent surgery is often required. To improve our understanding on how we may improve trauma care for patients with tibial shaft fractures, this study systematically reviewed all currently available evidence to assess the incidence of complications and rate of re-operations following intramedullary nailing of traumatic tibial fractures. Methods: Trip Database, Medline, Scopus and Cochrane Library were searched on September 7th, 2018. Searches were limited to English studies published after January 1st, 1998. Studies were included if authors included more than 50 patients treated with intramedullary nailing for traumatic tibial fractures. Inclusion of studies and critical appraisal of the evidence was performed by two independent authors. Incidence of complications and rate of re-operations were reported with descriptive statistics. Results: Fifty-one studies involving 8110 patients treated with intramedullary nailing for traumatic tibial fractures were included. Mean age of patients was 37.5 years. The most frequent complication was anterior knee pain (23%), followed by non-union (11%). Eighteen percent of patients required at least one subsequent surgery. The most frequent indication of subsequent surgery was screw removal due to pain or discomfort (9%). Dynamization of the nail to promote union was reported in 8% of the cases. Nail revision and bone-grafting to promote union were applied in 4% and 2% respectively. Discussion & Conclusion: Patients treated with intramedullary nailing for tibial fractures need to be consented for high probability of adverse events as anterior knee pain, subsequent surgical procedures and bone healing problems are relatively common. However, based on current data it remains difficult to identify specifiers and determinants of an individual patient with specific fracture characteristics at risk for complications. Future studies should aim to establish patient specific risks models for complications and re-operations, such that clinicians can anticipate them and adjust and individualize treatment strategies

Prospective Cohort Study to Investigate Factors Associated With Continued Immobilization of a Nondisplaced Scaphoid Waist Fracture

Purpose: The decision to continue immobilization of a nondisplaced scaphoid waist fracture is often based on radiographic appearance (despite evidence that radiographs are unreliable and inaccurate for diagnosing scaphoid union 6–12 weeks after fracture) and fracture tenderness (even though it is influenced by cognitive biases on pain). This may result in unhelpful additional immobilization. We studied nondisplaced scaphoid waist fractures to determine the factors associated with (1) the surgeon's decision to continue cast or splint immobilization at the first visit when cast removal was being considered; (2) greater pain on examination; and (3) the surgeon's concern about radiographic consolidation. Methods: We prospectively included 46 patients with a nondisplaced scaphoid waist fracture treated nonoperatively. At the first visit when cast removal was considered – after an average of 6 weeks of immobilization – patients rated pain during 4 examination maneuvers. The treating surgeon assessed union on radiographs and decided whether to continue or discontinue immobilization. Patients completed measures of the following: (1) the degree to which pain limits activities (Patient-Reported Outcome Measure Interactive System [PROMIS] Pain Interference Computer Adaptive Test [CAT], Pain Self-Efficacy Questionnaire-2); (2) symptoms of depression (PROMIS Depression CAT); and (3) upper extremity function (PROMIS Upper Extremity Function CAT). We used multivariable regression analysis to investigate the factors associated with each outcome. Results: Perceived inadequate radiographic healing and greater symptoms of depression were independently associated with continued immobilization. Pain during the examination was not associated with continued immobilization. Patient age was associated with pain on examination. Shorter immobilization duration was the only factor associated with the surgeon's perception of inadequate radiographic consolidation. Conclusions: Inadequate radiographic healing and greater symptoms of depression are associated with a surgeon's decision to continue cast or splint immobilization of a nondisplaced scaphoid waist fracture. Clinical relevance: Overreliance on radiographs and inadequate accounting for psychological distress may hinder the adoption of shorter immobilization times for nondisplaced waist fractures

Developing a machine learning algorithm to predict probability of retear and functional outcomes in patients undergoing rotator cuff repair surgery: protocol for a retrospective, multicentre study

INTRODUCTION: The effectiveness of rotator cuff tear repair surgery is influenced by multiple patient-related, pathology-centred and technical factors, which is thought to contribute to the reported retear rates between 17% and 94%. Adequate patient selection is thought to be essential in reaching satisfactory results. However, no clear consensus has been reached on which factors are most predictive of successful surgery. A clinical decision tool that encompassed all aspects is still to be made. Artificial intelligence (AI) and machine learning algorithms use complex self-learning models that can be used to make patient-specific decision-making tools. The aim of this study is to develop and train an algorithm that can be used as an online available clinical prediction tool, to predict the risk of retear in patients undergoing rotator cuff repair. METHODS AND ANALYSIS: This is a retrospective, multicentre, cohort study using pooled individual patient data from multiple studies of patients who have undergone rotator cuff repair and were evaluated by advanced imaging for healing at a minimum of 6 months after surgery. This study consists of two parts. Part one: collecting all potential factors that might influence retear risks from retrospective multicentre data, aiming to include more than 1000 patients worldwide. Part two: combining all influencing factors into a model that can clinically be used as a prediction tool using machine learning. ETHICS AND DISSEMINATION: For safe multicentre data exchange and analysis, our Machine Learning Consortium adheres to the WHO regulation 'Policy on Use and Sharing of Data Collected by WHO in Member States Outside the Context of Public Health Emergencies'. The study results will be disseminated through publication in a peer-reviewed journal. Institutional Review Board approval does not apply to the current study protocol