Infection-free Survival Research Articles

Clinical and Radiographic Outcomes of a Long Cementless Monobloc Stem for Revision Total Hip Arthroplasty Due to Chronic Periprosthetic Infection

BackgroundA long cementless monobloc stem is widely used for aseptic loosening, with satisfactory five-to-ten-year outcomes reported. Nonetheless, related studies on chronic periprosthetic joint infection (PJI) are scant. This study evaluated the clinical and radiographic outcomes of the stem in two-stage revisions due to PJI. MethodsThis prospective multicenter cohort study consisted of patients from three medical centers who were enrolled in a single arm from January 2017 to May 2022. All patients were diagnosed with chronic PJI based on International Consensus Meeting (ICM) criteria and underwent two-stage revisions using a long monobloc cementless revision stem. Among 44 patients, 37 (12 women and 25 men) completed an average follow-up of 35.6 months (range, 14 to 75). The primary outcome was the stability of the stem; secondary outcomes included infection eradication, Harris hip score, leg length discrepancy, major complications, and isolated pathogens at intraoperative cultures. ResultsAt one year after revision, the infection-free prosthesis survival rate was 97.3% (95% CI [confidence interval]: 96.4 to 98.2%). At the last follow-up, the mean subsidence was 2.9 ± 2.1 mm (range, 0.8 to 4.8). Postoperative leg length discrepancy averaged −4.6 ± 4.9 mm (range, −16 to 0). The Engh score averaged 14.1 ± 6.9 (range, 0 to 22). The Harris hip score improved from a preoperative average of 35.7 ± 8.5 (range, 12 to 50) to 80.4 ± 9.3 (range, 58 to 92) at the 1-year postoperative follow-up (P < 0.01). ConclusionThe long cementless monobloc stem used in the current study presents a feasible option for two-stage revision in cases of chronic PJI. The bone ingrowth and stability could be observed within the short follow-up time.

Benefits and Adverse Events Associated With Extended Antibiotic Use for One Year Following Periprosthetic Joint Infection in Total Knee Arthroplasty: A Prospective Cohort Analysis.

Periprosthetic joint infections (PJIs) are common and serious complications following knee and hip arthroplasty. Our previous retrospective study suggested extended antibiotics following debridement, antibiotics, and implant retention (DAIR) decreased failure rates and were not associated with increased adverse events (AEs) as compared to a standard 6 weeks of antibiotic therapy. Further, extended antibiotics beyond one year did not provide additional benefits. These observations were tested in this prospective cohort study. A prospective cohort of patients who underwent DAIR for total knee arthroplasty PJI and received primary antibiotics were compared to patients who received primary antibiotics combined with extended antibiotics for one year. Participants had a minimum of 2-year follow-up after the final dose of antibiotics. A prospective cohort of 79 patients was followed, where 39 participants (52.7%) received primary antibiotics and 35 participants (47.3%) received both primary and extended antibiotics following DAIR. Multivariable time-to-event analyses revealed that extended antibiotic use was an independent predictor of treatment success. Infection-free survival differed significantly between the two treatment regimens, as the hazard of PJI failure was significantly lower for extended antibiotics as compared to primary antibiotics alone (adjusted hazard ratio [HR]= 0.46 [0.24 to 0.87], P= 0.017). The AE rates did not significantly differ between patients treated with primary antibiotics only versus primary combined with extended antibiotics. This prospective cohort study supports our previous observations that extended antibiotics for one year were associated with lower failure rates as compared to primary antibiotics alone. Extended antibiotics after primary antibiotics were not found to be associated with increased AEs as compared to only primary antibiotics.

Unsuspected Positive Intra-Operative Cultures in Aseptic Revision Hip Arthroplasty: Prevalence, Management, and Infection-Free Survivorship

BackgroundThis study aimed to describe the management and outcomes of aseptic revision total hip arthroplasty (arTHA) with unsuspected intra-operative positive cultures (UPCs) compared to those with sterile cultures. MethodsA single tertiary center’s institutional database was retrospectively reviewed for arTHA from January 2013 to October 2023. Pre-operative Musculoskeletal Infection Society (MSIS) scores were assigned to patients based on available infectious workup, and those who met the criteria for periprosthetic infection (PJI), received antibiotic spacers, or had less than 1-year follow-up were excluded. Patients were grouped and compared according to intra-operative culture results: sterile cultures, one UPC with a new organism, one UPC with the same organism as prior PJI, ≥ two UPCs with different organisms, and ≥ two UPCs with the same organism. ResultsThere was a total of 604 arTHAs included in this study, of which 0.8% [five of 604] had ≥ two UPCs with different organisms, 1.5% [9 of 604] had ≥ 2 UPCs with the same organism, 9.8% [59 of 604] had one UPC with a new organism, 0.2% [one of 604] had 1 UPC with an organism from prior PJI, and 87.7% [530 of 604] of patients had sterile cultures. When comparing 5-year infection-free survival between patients who had one UPC with a new organism and sterile cultures, there was no difference (P = 0.40); however, patients who had ≥ two UPCs with different organisms (P < 0.001), patients who had ≥ two UPCs with the same organism (P = 0.001), and patients who had one UPC of an organism from prior PJI (P < 0.001) had statistically worse infection-free survival compared to patients with sterile cultures. ConclusionInfection-free survival at five years was similar between patients who had one UPC with a new organism and those who had sterile cultures; however, ≥ two UPCs and a history of PJI are both significant risk factors for re-revision for infection after arTHA.

Evaluating the impact of surgery sequence on infection rates in hip or knee arthroplasty: does sequence matter?

The potential influence of surgical sequence of elective hip-and-knee reconstructive surgery in relation to an infection-related procedure on postoperative infection rates is not clearly understood. Therefore, we aimed to examine the impact of surgical sequence on the incidence of postoperative infections within one-year and the longest available follow-up period in patients undergoing hip-and-knee reconstructive surgery. A case-control study with propensity matching was utilized to examine elective surgeries conducted at Sunnybrook Holland Orthopaedic & Arthritic centre, Toronto, Canada between 2015 and 2018. We determined and categorized them based on their operating room (OR) sequence in relation to an infected case; the cases were those performed right after (post-infection cohort), and the controls were those performed before an infection-related procedure in the same OR (pre-infection cohort). We employed survival analysis to compare the infection incidence within one year and at the longest available follow-up among the propensity-matched cohort. A total of 13,651 cases were identified during the four year period. We successfully matched 153 cases (21 post-infection and 132 pre-infection) using propensity scores. Demographic and clinical characteristics were balanced through matching. Kaplan-Meier survival analysis showed no significant difference in infection-free survival within one year and at a median follow-up of 2.2 years [interquartile range 0.9-5.0] between surgeries conducted before and after infected cases (both log-rank p-values = 0.4). The hazard ratios for infection within one year and the longest follow-up period were both 0.37 [95%Confidence Interval 0.03-4.09, p = 0.418], as no more events occurred after one year. The sequence of surgical procedures, whether or not an elective arthroplasty or lower limb reconstructive procedure occurs before or after an infection-related case in the same OR, does not significantly affect postoperative infection rates. This finding supports the efficacy of the current infection control measures and suggests a reconsideration of surgical scheduling standards.

Prognostic Implications of Unexpected Positive Intraoperative Cultures in Two-Stage Knee Arthroplasty Reimplantations: A Minimum Five-Year Retrospective Analysis

BackgroundThe clinical challenge of unexpected positive intraoperative cultures (UPICs) persists in 2-stage resection arthroplasty for managing periprosthetic joint infections (PJIs) following total knee arthroplasty.(TKA). This study aimed to investigate the incidence of UPICs during the definitive reimplantation phase of 2-stage resection arthroplasty of the knee and to assess both the infection-free and revision-free survivorship of the implanted prosthesis. MethodsThis retrospective study included 450 2-stage resection arthroplasties of primary knee prostheses performed between January 2012 and April 2017. Patients were excluded if they: (1) underwent three or more staged resections, (2) had ambiguous clinical documentation or deviated from the 2-stage protocol, or (3) underwent revision arthroplasty prior to the PJI. Additionally, patients presumed aseptic before the second-stage reimplantation were excluded if they lacked joint aspiration or met the 2011 Musculoskeletal Infection Society criteria for PJI before implantation. ResultsAfter exclusions, 300 patients were analyzed. Among them, 14% had UPIC during the second-stage reimplantation. The follow-up time was 2,316 (range, 1,888 to 3,737) days and 2,531 (range, 1,947 to 3,349) days for UPIC and negative intraoperative culture (NIC) groups, respectively. Rerevision due to subsequent PJI occurred in 26.2% of UPIC patients and 15.1% of NIC patients. The 2-year infection-free survival rates for the NIC, one UPIC, and ≥ two UPIC cohorts were 99.5, 98.2, and 94.3%, respectively, while the 5-year survival rates were 92.1, 91.1, and 54.3%, respectively. The unfavorable survivorship was significantly different in multiple UPIC cases (P < 0.001). Multiple UPICs with pathogens consistent with the first-stage findings were strongly associated with the risk of reinfection (P < 0.001). ConclusionsAn UPIC was identified in 14% of second-stage reimplantations. Patients who had multiple UPICs demonstrated truncated survivorship and suboptimal outcomes relative to the NIC and single UPIC cohorts, especially with pathogen consistency to the first-stage surgery. Level of evidenceIII.

Tranexamic Acid Led to Improved Safety of Total Knee Arthroplasty in Jehovah’s Witness Patients: A Multicentered Matched Study

BackgroundThis study aimed to evaluate the safety of total knee arthroplasty (TKA) in Jehovah’s Witness patients compared to non-Jehovah’s Witness patients using standard perioperative TKA protocols and assess the role of tranexamic acid (TXA) in managing blood loss in this population. MethodsPatients undergoing TKA between 2011 and 2021 at 2 tertiary academic centers were retrospectively reviewed. Patient demographics, preoperative and postoperative hematologic laboratory values, intraoperative TXA use, 90-day postoperative complications, and subsequent revisions were collected. These variables were then compared between propensity score–matched cohorts at a 2:1 ratio of those who did not identify as Jehovah’s Witness to those who did. Regression analysis was used to determine the effect of intraoperative TXA on hemoglobin (hgb) shift. ResultsAfter applying exclusion criteria and matching, the TKA outcomes of 316 non-Jehovah’s Witness patients and 152 Jehovah’s Witness patients were analyzed. Univariate analysis suggested that non-Jehovah’s Witness patients and Jehovah’s Witness patients had similar preoperative and postoperative hgb, hgb shift, and hematocrit. Only 1 (0.8%) Jehovah’s Witness patient reached an hgb < 8.0 mg/dL postoperatively. Multivariate logistic regression suggested that Jehovah’s Witness patients did not have increased odds of reaching an hgb < 8.0 mg/dL (odds ratio = 0.99 [0.96, 1.02]; P = 0.42). Multivariate linear regression suggested that intraoperative TXA was positively correlated with hgb shift and thus a smaller decrease in hgb from pre-TKA to post-TKA (β = 0.38 [0.06, 0.69]; P = 0.02). Additionally, Jehovah’s Witness patients had excellent revision-free (95% [91, 99]) and infection-free (98% [95, 100]) survival at 8 years. ConclusionsStandard perioperative TKA protocols are safe for Jehovah’s Witness patients who do not have the need for transfusion, especially with appropriate preoperative hgb levels and the use of intraoperative TXA. Furthermore, these patients have excellent survivorship at 5 and 8 years of follow-up. Level of EvidenceLevel III.

The Cost-effectiveness of Valganciclovir Prophylaxis Versus Preemptive Therapy in CMV R+ Kidney Transplant Recipients Over the First Year Posttransplantation.

In kidney transplant recipients with positive serology (R+) for the cytomegalovirus (CMV), 2 strategies are used to prevent infection, whose respective advantages over the other are still debated. This study aimed to evaluate the cost-effectiveness and cost utility of antiviral prophylaxis against CMV versus preemptive therapy, considering CMV infection-free survival over the first year posttransplantation as the main clinical outcome. Clinical, laboratory, and economic data were collected from 186 kidney transplant patients CMV (R+) included in the cohort study (85 patients who benefited from CMV prophylaxis and 101 from preemptive therapy). Costs were calculated from the hospital perspective and quality-adjusted life years (QALYs) using the EQ5D form. Using nonparametric bootstrapping, the incremental cost-effectiveness ratio (ICER) and cost utility were estimated (euros) for each case of infection avoided and each QALY gained for 1 y, respectively. Prophylaxis significantly decreased the risk of CMV infection over the first year posttransplantation (hazard ratio 0.22, 95% confidence interval = 0.12-0.37, P < 0.01). Compared with preemptive therapy, prophylaxis saved financial resources (€1155 per patient) and was more effective (0.42 infection avoided per patient), resulting in an ICER = €2769 per infection avoided. Prophylaxis resulted in a net gain of 0.046 in QALYs per patient and dominated over preemptive therapy with €1422 cost-saving for 1 QALY gained. This study shows that CMV prophylaxis, although considered as a more expensive strategy, is more cost-effective than preemptive therapy for the prevention of CMV infections in renal transplant patients. Prophylaxis had a positive effect on quality of life at reasonable costs and resulted in net savings for the hospital.

Can Periprosthetic Joint Infection of Tumor Prostheses Be Controlled With Debridement, Antibiotics, and Implant Retention?

Two-stage revision for periprosthetic joint infection (PJI) in patients who have undergone segmental replacement of the distal femur or proximal tibia after tumor resection can be associated with considerable morbidity, pain, and risk of complications because the procedure often results in removal of long, well-fixed stems from the diaphysis. A less-aggressive surgical approach, such as debridement, antibiotics, and implant retention (DAIR), may be attractive to patients and surgeons because of less morbidity, but the likelihood of eradicating infection in comparison to the traditional two-stage revision is not well established for oncology patients. Furthermore, the relative risk of subsequent amputation for DAIR versus two-stage revision has not been defined for this population. (1) How does DAIR compare with two-stage revision in terms of infection control for patients with distal femoral or proximal tibial segmental modular endoprostheses? (2) Is DAIR as an initial procedure associated with an increased risk of amputation compared with two-stage revision for infection? From the longitudinally maintained orthopaedic oncology surgical database at our institution, we identified 69 patients who had been treated for a clinical diagnosis of PJI at the knee between 1993 and 2015. We excluded 32% (22) of patients who did not meet at least one of the major criteria of the Musculoskeletal Infection Society (MSIS) for PJI, 3% (2) of patients who underwent immediate amputation, 3% (2) of patients who had a follow-up time of < 24 months, and 7% (5) of patients who did not have a primary tumor of the distal femur or proximal tibia. The study consisted of 38 patients, of whom eight underwent two-stage revision, 26 underwent DAIR, and four underwent extended DAIR (removal of all segmental components but with retention of stems and components fixed in bone) for their initial surgical procedure. To be considered free of infection, patients had to meet MSIS standards, including no positive cultures, drainage, or surgical debridement for a minimum of 2 years from the last operation. Factors associated with time-dependent risk of infection relapse, clearance, amputation, and patient survival were analyzed using Kaplan-Meier survivorship curves and the log-rank test to compare factors. Association of demographic and treatment factors was assessed using chi-square and Fisher exact tests. Continuous infection-free survival at 5 years was 16% (95% CI 2% to 29%) for patients undergoing DAIR compared with 75% (95% CI 45% to 100%) for patients undergoing two-stage revision (p = 0.006). The median (range) number of total surgical procedures was 3 per patient (1 to 10) for DAIR and 2 (2 to 5) for two-stage revision. Twenty-nine percent (11 of 38) of patients eventually underwent amputation. Survival without amputation was 69% (95% CI 51% to 86%) for DAIR compared with 88% (95% CI 65% to 100%) for two-stage revision at 5 years (p = 0.34). The cumulative proportion of patients achieving infection-free status (> 2 years continuously after last treatment) and limb preservation was 58% (95% CI 36% to 80%) for patients initially treated with DAIR versus 87% (95% CI 65% to 100%) for patients first treated with two-stage revision (p = 0.001). Infection control was better with two-stage revision than DAIR. The chance of eventual clearance of infection with limb preservation was better when two-stage revision was chosen as the initial treatment. However, the loss to follow-up in the two-stage revision group would likely make the true proportion of infection control lower than our estimate. Our experience would suggest that the process of infection eradication is a complex and difficult one. Most patients undergo multiple operations. Nearly one-third of patients eventually underwent amputation, and this was a serious risk for both groups. While we cannot strongly recommend one approach over the other based on our data, we would still consider the use of DAIR in patients who present with acute short duration of symptoms (< 3 weeks), no radiographic signs of erosion around fixed implants, and organisms other than Staphylococcus aureus. We would advocate the extended DAIR procedure with removal of all segmental or modular components, and we would caution patients that there is a high likelihood of needing further surgery. A prospective trial with strict adherence to indications may be needed to evaluate the relative merits of an extended DAIR procedure versus a two-stage revision. Level III, therapeutic study.

Above-knee amputation shows higher complication and mortality rates in line with lower functional outcome compared to knee arthrodesis in severe periprosthetic joint infection

AimsIn cases of severe periprosthetic joint infection (PJI) of the knee, salvage procedures such as knee arthrodesis (KA) or above-knee amputation (AKA) must be considered. As both treatments result in limitations in quality of life (QoL), we aimed to compare outcomes and factors influencing complication rates, mortality, and mobility.MethodsPatients with PJI of the knee and subsequent KA or AKA between June 2011 and May 2021 were included. Demographic data, comorbidities, and patient history were analyzed. Functional outcomes and QoL were prospectively assessed in both groups with additional treatment-specific scores after AKA. Outcomes, complications, and mortality were evaluated.ResultsA total of 98 patients were included, 52 treated with arthrodesis and 47 with AKA. The mean number of revision surgeries between primary arthroplasty and arthrodesis or AKA was 7.85 (SD 5.39). Mean follow-up was 77.7 months (SD 30.9), with a minimum follow-up of two years. Complications requiring further revision surgery occurred in 11.5% of patients after arthrodesis and in 37.0% of AKA patients. Positive intraoperative tissue cultures obtained during AKA was significantly associated with the risk of further surgical revision. Two-year mortality rate of arthrodesis was significantly lower compared to AKA (3.8% vs 28.3%), with age as an independent risk factor in the AKA group. Functional outcomes and QoL were better after arthrodesis compared to AKA. Neuropathic pain was reported by 19 patients after AKA, and only 45.7% of patients were fitted or were intended to be fitted with a prosthesis. One-year infection-free survival after arthrodesis was 88.5%, compared to 78.5% after AKA.ConclusionAbove-knee amputation in PJI results in high complication and mortality rates and poorer functional outcome compared to arthrodesis. Mortality rates after AKA depend on patient age and mobility, with most patients not able to be fitted with a prosthesis. Therefore, arthrodesis should be preferred whenever possible if salvage procedures are indicated.Cite this article: Bone Joint J 2024;106-B(7):669–679.

Unsuspected Positive Intraoperative Cultures in Aseptic Revision Knee Arthroplasty: Prevalence, Management, and Infection-Free Survivorship

BackgroundThe purpose of this study was to evaluate the management and outcomes of aseptic revision total knee arthroplasty (arTKA) with unsuspected positive cultures (UPCs) compared to those with sterile cultures. MethodsThe institutional database at a single tertiary center was retrospectively reviewed for arTKA from January 2013 to October 2023. Patients who met Musculoskeletal Infection Society criteria for periprosthetic joint infection (PJI) based on available preoperative infectious workup, received antibiotic spacers, or did not have at least 1 year of follow-up were excluded. Patients were stratified based on intraoperative cultures into 4 cohorts: sterile cultures, 1 UPC, ≥ 2 UPCs with different organisms, and ≥ 2 UPCs with the same organism. Univariable analyses were used to compare these groups. Kaplan-Meier survivorship analysis assessed infection-free survival at 5 years, and Cox proportional hazards regressions were used to evaluate factors that influence infection-free survival. A total of 691 arTKAs at a mean follow-up of 4.2 years were included in the study. Of these, 49 (7.1%) had 1 UPC with a new organism, 10 (1.4%) had ≥2 UPCs of the same organism, and 2 (0.2%) had ≥2 UPCs with different organisms. ResultsPostoperative antibiotics were prescribed to 114 (16.5%) patients—13 (26.5%) with 1 UPC, 6 (60.0%) with ≥2 UPCs of the same organism, and 0 (0.0%) of patients who had ≥2 UPCs of different organisms. There were no differences in infection-free survival at 5 years between patients who had sterile cultures and 1 UPC (96 versus 89%; P = .39) nor between sterile cultures and ≥2 UPCs of different organisms (96 versus 100%; P < .72). However, patients who had ≥2 UPCs of the same organism had significantly worse infection-free survival at 5 years compared to patients who had sterile cultures (58 versus 96%; P < .001). Cox proportional hazards regression suggested that when adjusting for covariates, an American Society of Anesthesiologists classification of ≥3 (hazard ratio [HR] = 3.1; P = .007), ≥2 UPCs of the same organism (HR = 11.0; P < .001), 1 UPC (HR = 4.2; P = .018), and arTKA with hinge constructs (HR = 4.1; P = .008) were associated with increased risk of rerevision for PJI. ConclusionsPatients who had 1 UPC or ≥2 UPCs with different organisms had similar infection-free survival at 5 years as patients who had sterile cultures. However, patients who had ≥2 UPCs of the same organism had significantly worse infection-free survival at 5 years. Overall, 1 UPC or ≥2 UPCs of the same organism at the time of arTKA may suggest the patient is at higher risk of rerevision for PJI. More studies are needed to determine what interventions can be implemented to mitigate this risk.

#1739 Combination rituximab &amp; low-dose IV cyclophosphamide induction therapy for severe multi-system eosinophilic granulomatosis with polyangiitis

Abstract Background and Aims Current guidelines advise rituximab (RTX) or cyclophosphamide treatment for organ-threatening disease in eosinophilic granulomatosis with polyangiitis (EGPA). However, conventional treatment is often limited by partial efficacy, toxicity, high relapse rate and steroid dependency. We investigate the use of a combined RTX, low-dose cyclophosphamide, and steroid regimen for treatment of severe EGPA. Method Single-centre retrospective cohort study of patients treated with a combination induction regimen for severe EGPA (with kidney, cardiac or neurological involvement) between 2012-23. Data reported as median (±IQR) Results Eighteen patients (10 male; age 56 years [52-62]) are included. At treatment, BVAS was 16.3 [14-20], peak eosinophil count 9.3 × 109/L [5-13], C-reactive protein (CRP) 122 mg/L [80-193]. Eleven cases were ANCA positive (10 MPO-, 1 PR3-ANCA.) The proportions of patients affected by active/new respiratory, ENT, neurological, and gastrointestinal disease were 18/18 (100%), 14/18 (78%), 11/18 (61%), and 1/18 (6%), respectively. 11/18 (61%) had cardiac involvement (troponin 10345 ng/L [1240-7621]) and 6/18 (33%) had necrotising glomerulonephritis confirmed by renal biopsy (creatinine 123 µmol/L [83-167]). Cumulative cyclophosphamide dose was 3.5g [3.0-3.5] and total RTX dose was 2g. Initial prednisolone dose was 0.5-1.0 mg/kg/day, and this was rapidly weaned to 5 mg daily at a median time of 6.1 months [3.9-7.2], and 9/18 (50%) had steroids withdrawn completely by 11.7 months [4.6-20.6]. First-line maintenance treatment was azathioprine or MMF. By 6 months, all achieved disease remission as assessed by BVAS (all 0) and improved laboratory parameters: CRP 1 mg/L, eosinophil count 0.1 × 109/L, and ANCA testing negative. In those with renal disease, kidney function improved or stabilised in all (creatinine 95 µmol/L). In those with cardiac disease (11/18), magnetic resonance imaging was performed at baseline and at follow up (median time of 3.7 months) in all patients. Of these, 9/11 (82%) had oedema on initial scan and this improved in all cases; 10/11 (91%) had late gadolinium enhancement at baseline, which persisted in every case, though with significantly lower burden. The median follow-up period was 38 months [14-55]. At 1, 3 and 5 years, 100%, 92% and 76% of patients were in sustained remission (Fig. 1A). Three patients experienced relapse; one patient had major relapse with skin involvement requiring reinduction treatment; two patients had minor ENT relapse requiring retreatment with glucocorticoids. Infection-free survival at 1, 3 and 5 years was 94%, 78%, 62%, respectively (Fig. 1B). There were no deaths. Conclusion This regimen provided rapid disease control in patients with severe multi-system EGPA, including those with life-threatening cardiac manifestations, and enabled rapid glucocorticoid tapering and withdrawal. Disease-free remission was sustained during long-term follow up. Combination induction regimens may have a role in the treatment of organ-threatening disease in EGPA.

#2744 Analysis of bacteremia and mortality in patients with tunneled catheter for hemodialysis: a 14-years observational study

Abstract Background and Aims Infections are a leading cause of morbidity and mortality in hemodialysis patients. Tunneled catheters (TC) have been associated with increased risk of infection and death, but mortality rates are not widely reported. Our study aimed to analyse catheter infection-free survival and mortality of patients with this vascular access. Method This is a retrospective study of all TC inserted during the period of 1 January 2005 to 31 December 2019. The TC were inserted by nephrologists, following a preimplantation protocol agreed with the Infectious Diseases Service. Patients were followed up from the tunneled catheter insertion until the study end date (December 31, 2020), TC related bacteremia or died. Results In the 14-year period under study, 406 TC were implanted in 325 patients. A total of 85 tunneled catheter related bacteremia were diagnosed, resulting in an incidence of 0.40 per 1000 catheter days (81.1% after 6 months of implantation). The predominant microorganisms isolated were Gram-positive organisms: Staphylococcus epidermidis (48.4%); Staphylococcus aureus (28.0%). During the study, a total of 145 patients had the TC removed or exchanged due different causes. The main reasons for catheter removal were the adequate development and use of the arteriovenous fistula (48, 33.1%) and discharge from hemodialysis due to recovery of renal function, transfer to peritoneal dialysis or renal transplantation (47, 32.4%). Only in 26 (17.9%) patients, the TC was removed due to bacteremia at a median of 4.8 (1.0-8.0) days from the bacteremia. The median time to catheter removal for non-infection-related reasons was 448 (185-910) days, without significant differences with the TC related bacteremia group [430 (116-695)] (p=0.83). The 30-day mortality rate from the first TC related bacteremia was 8.7%. During the study period, a total of 168 (51.7%) patients died for different causes. Conclusion The incidence of bacteremia in our study was low and did not seem to have a relevant impact on catheter survival. The global mortality rate was similar to that reported in European registries for patients on renal replacement therapy. An implantation and management protocol, strict in prophylactic measures, could reduce the incidence of bacteremia and reduce its morbidity and mortality.

Characteristics and Outcome of Vascular Graft Infections: A Risk Factor and Survival Analysis.

Vascular graft infection (VGI) is a serious complication after implantation of arterial vascular grafts. Optimal surgical and pathogen-specific antimicrobial treatment regimens for VGI are largely unknown. We evaluated patients with arterial VGI according to onset, location, microbiological and imaging characteristics, and surgical and antimicrobial treatment and performed an outcome evaluation. Consecutive patients with VGI treated in 2 hospitals from 2010 through 2020 were retrospectively analyzed. Uniform definition criteria and standardized outcome evaluation were applied. Logistic regression was used for multiple analysis; survival analysis was performed with Kaplan-Meier analysis and a log-rank test. Seventy-eight patients with VGI were included: 30 early-onset cases (<8 weeks after graft implantation) and 48 late-onset cases, involving 49 aortic and 29 peripheral grafts. The median time from initial implantation to diagnosis of VGI was significantly longer in aortic than peripheral VGIs (363 vs 56 days, P = .018). Late-onset VGI (odds ratio [OR], 7.3; P = .005) and the presence of surgical site infection/complication (OR, 8.21; P = .006) were independent risk factors for treatment failure. Surgical site infection/complication was associated with a higher risk for early-onset VGI (OR, 3.13; P = .040). Longer infection-free survival was observed in cases where the infected graft was surgically removed (P = .037). This study underlines the importance of timely diagnosis of VGI and preventing surgical site infections/complications at graft implantation. It highlights the complexity of infection eradication, especially for late-onset infections, and the importance of adequate antimicrobial and surgical treatment.

Multisite Study of the Management of Musculoskeletal Infection after Trauma – The MMUSKIT Study

Abstract Background The optimal duration and choice of antibiotic for fracture-related infection (FRI) is not well-defined. This study aimed to determine whether antibiotic duration (≤6 weeks versus &amp;gt;6 weeks) is associated with infection-free and surgery-free survival. The secondary aim was to ascertain risk factors associated with surgery- and infection-free survival. Methods We performed a multicenter, retrospective study of patients diagnosed with FRI between 2013 and 2022. The association between antibiotic duration and surgery-free and infection-free survival was assessed using Cox proportional hazard models. Models were weighted by the inverse of the propensity score, calculated using a priori variables of hardware removal; infection due to; Staphylococcus aureus, Staphylococcus lugdunensis, Pseudomonas or Candida species; and flap coverage. Multivariable Cox proportional hazard models were run with additional covariates including initial pathogen, need for flap, and hardware removal. Results Of 96 patients, 54 (56.3%) received ≤6 weeks and 42 (43.7%) received &amp;gt;6 weeks of antibiotics. There was no association between longer antibiotic duration and surgery-free survival (HR: 0.95; 95% CI: 0.65-1.38; p = 0.78) or infection-free survival (HR: 0.77; 95% CI: 0.30-1.96; p = 0.58). Negative culture was associated with increased hazard of reoperation or death (HR: 3.52; 95% CI: 1.99-6.20; p &amp;lt; 0.001) and reinfection or death (HR: 3.71; 95% CI: 1.24-11.09; p &amp;lt; 0.001). Need for flap coverage had an increased hazard of reoperation or death (HR: 3.24; 95% CI: 1.61-6.54; p = 0.001). Conclusions The ideal duration of antibiotics to treat FRI is unclear. In this multicenter study there was no association between antibiotic treatment duration and surgery-free or infection-free survival.

Outcomes of rotating versus pure hinge knee arthroplasty in the setting of one-stage exchange for periprosthetic joint infection.

Rotating or pure hinge knee prostheses are often used in case of periprosthetic joint infection (PJI). Five-year survival data of rotating hinge implants ranging from 52 to 90%, whereas pure hinge data are sparse. This study describes the results of both hinge knee prostheses after one-stage septic exchange. One hundred sixty-seven one-stage septic exchanges of a primary unconstrained total knee arthroplasty (TKA) to a cemented hinge prosthesis (117 rotating and 50 pure hinge TKAs) performed between 2008 and 2017 were retrospectively reviewed. Exclusion criteria were stem extensions or augments used in primary TKA, history of extensor mechanism reconstruction, and a follow-up less than twoyears after surgery. Rates of reinfection, mechanical failures, and all-cause revision-free survival data were documented. At fiveyears, the all-cause revision-free survival was 77% (95% CI 69 to 82). Thirty-one patients (19%) had further revision for aseptic reasons. In the rotating hinge group, the mechanical failure rate was more than twice as high as in the pure hinge group (13% vs 6%), significantly influenced by higher body weight. At a mean follow-up of 6.7years, 21 (13%) patients had a reinfection and underwent a further surgery. Reinfection rates did not differ between the two groups. The use of hinge TKA in the revision of PJI shows favourable fiveyear infection-free and all-cause revision-free survival rates of 91% and 77%, respectively. Our study showed poorer results of the rotating hinge design. These results may help surgeons to choose proper implants in case of septic knee revision.

Symptoms and Severity of COVID-19 in Patients with Immune-Mediated Inflammatory Diseases: Experience of a University Medical Center.

The pandemic situation of the novel coronavirus (severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) and its associated disease (coronavirus disease 2019 (COVID-19)) represents a challenging condition with a plethora of aspects. The course of COVID-19 in patients with immune-mediated inflammatory diseases (IMID) such as inflammatory bowel disease (IBD) and rheumatic diseases (RD) is not well known. Our study is one step toward closing this gap by collecting data on vaccination rates, infection-free survival, and individual symptom severity. We conducted a prospective questionnaire-based study between April 2022 and October 2022 at our university hospital. Outward patients over the age of 18 years were screened for participation and reported about their infection/infection-free survival since the start of the pandemic. Finally, 156 patients were included in the study, 117 (75.0%) of which had inflammatory bowel disease and 39 (25.0%) patients with rheumatic disease. Altogether, 143 (91.7%) persons had received at least one vaccination against SARS-CoV-2. A total of 153 patients provided information regarding their COVID-19 history: 81 patients (52.0%) self-reported about their SARS-CoV-2 infection. In general, courses of infection were mild: only two patients (2.5% of patients with reported COVID-19) were hospitalized due to COVID-19 with one (1.2%) of the two needing intensive care. Asymptomatic COVID-19 had been described by 7 persons (8.6% of patients with reported COVID-19). Acute COVID-19 was accompanied by fatigue/tiredness in 58 persons (71.6% of patients with history of COVID-19) as the most frequent symptom. Other complaints were common cold (55 patients = 67.9%), cough (51 patients = 63.0%), headache (44 patients = 54.3%), and fever (35 patients = 43.2%). Stratified by vaccination status (unvaccinated vs. at least once vaccinated), the time to infection differed significantly (logrank test: p = 0.04, Chi2 4.1). At least once vaccinated people had a median COVID-19-free survival of 28.5 months (confidence interval (CI): 23.6 months-not reached). Without any vaccination, the estimated time to infection was 25.1 months (CI: 23.6 months-not reached). Our IMID patients have a high rate of vaccination against SARS-CoV-2. Data show a significantly longer infection-free survival in vaccinated IMID patients as compared to unvaccinated patients. Discrimination between symptoms of COVID-19 and a concomitant inflammatory disease is difficult as complaints might be overlapping. This trial is registered with DRKS00028880.

Using serological diagnostics to characterize remaining high-incidence pockets of malaria in forest-fringe Cambodia

BackgroundOver the last decades, the number of malaria cases has drastically reduced in Cambodia. As the overall prevalence of malaria in Cambodia declines, residual malaria transmission becomes increasingly fragmented over smaller remote regions. The aim of this study was to get an insight into the burden and epidemiological parameters of Plasmodium infections on the forest-fringe of Cambodia.Methods950 participants were recruited in the province of Mondulkiri in Cambodia and followed up from 2018 to 2020. Whole-blood samples were processed for Plasmodium spp. identification by PCR as well as for a serological immunoassay. A risk factor analysis was conducted for Plasmodium vivax PCR-detected infections throughout the study, and for P. vivax seropositivity at baseline. To evaluate the predictive effect of seropositivity at baseline on subsequent PCR-positivity, an analysis of P. vivax infection-free survival time stratified by serological status at baseline was performed.ResultsLiving inside the forest significantly increased the odds of P. vivax PCR-positivity by a factor of 18.3 (95% C.I. 7.7–43.5). Being a male adult was also a significant predictor of PCR-positivity. Similar risk profiles were identified for P. vivax seropositivity. The survival analysis showed that serological status at baseline significantly correlated with subsequent infection. Serology is most informative outside of the forest, where 94.0% (95% C.I. 90.7–97.4%) of seronegative individuals survived infection-free, compared to 32.4% (95% C.I.: 22.6–46.6%) of seropositive individuals.ConclusionThis study justifies the need for serological diagnostic assays to target interventions in this region, particularly in demographic groups where a lot of risk heterogeneity persists, such as outside of the forest.

Pre-transplant crossmatch-negative donor-specific anti-HLA antibody predicts acute antibody-mediated rejection but not long-term outcomes in kidney transplantation: an analysis of the Korean Organ Transplantation Registry.

Pre-transplant donor-specific anti-human leukocyte antigen antibody (HLA-DSA) is a recognized risk factor for acute antibody-mediated rejection (ABMR) and allograft failure. However, the clinical relevance of pre-transplant crossmatch (XM)-negative HLA-DSA remains unclear. We investigated the effect of XM-negative HLA-DSA on post-transplant clinical outcomes using data from the Korean Organ Transplantation Registry (KOTRY). This study included 2019 living donor kidney transplant recipients from 40 transplant centers in South Korea: 237 with HLA-DSA and 1782 without HLA-DSA. ABMR developed more frequently in patients with HLA-DSA than in those without (5.5% vs. 1.5%, p<0.0001). Multivariable analysis identified HLA-DSA as a significant risk factor for ABMR (odds ratio = 3.912, 95% confidence interval = 1.831-8.360; p<0.0001). Furthermore, the presence of multiple HLA-DSAs, carrying both class I and II HLA-DSAs, or having strong HLA-DSA were associated with an increased incidence of ABMR. However, HLA-DSA did not affect long-term clinical outcomes, such as allograft function and allograft survival, patient survival, and infection-free survival. Pre-transplant XM-negative HLA-DSA increased the risk of ABMR but did not affect long-term allograft outcomes. HLA-incompatible kidney transplantation in the context of XM-negative HLA-DSA appears to be feasible with careful monitoring and ensuring appropriate management of any occurrence of ABMR. Furthermore, considering the characteristics of pre-transplant XM-negative HLA-DSA, the development of a more detailed and standardized desensitization protocol is warranted.

Risk factors for hypogammaglobulinemia and association with relapse and severe infections in ANCA-associated vasculitis: A cohort study.

B-cell depletion induced by rituximab (RTX) in ANCA-associated vasculitis (AAV) is a risk factor for hypogammaglobulinemia. Aggregating data on gammaglobulin levels kinetics during RTX and its association with the risk of relapse and severe infection is of interest. Gammaglobulin levels were collected before induction therapy and during RTX maintenance therapy. We used different definitions of gammaglobulin decline: 1/gammaglobulin levels <6g/L after induction; 2/>25% decline in gammaglobulin levels between induction and maintenance, and 3/both. Our primary objective was the impact of gammaglobulin decline on the risk of relapse and severe infections. We included 98 patients. Patients with gammaglobulin level <6g/L after induction and gammaglobulin decline >25% were older (OR 3.9; 95%CI 1.1-16.1), had more frequently baseline gammaglobulin levels <10g/L (OR 6.0; 95%CI 1.7-25.8) and received more frequent pulses of methylprednisolone at induction (OR 4.6; 95%CI 1.3-18.5). Severe infection-free survival was significantly poorer in patients with both gammaglobulin <6g/L and gammaglobulin decline >25% (adjusted HR 2.3; 95%CI 1.0-5.1) and in those who received pulses of methylprednisolone (HR 5.6; 95%CI 2.3-13.4). Gammaglobulin decline was in contrast not associated with the risk of relapse. Older age, low gammaglobulin levels and pulses of methylprednisolone at induction increase the likelihood of gammaglobulin decline after induction therapy. Such decline was associated with an increased risk of severe infections but not lower risk of vasculitis relapse. Pulses of methylprednisolone at induction had an independent negative impact on gammaglobulin levels and the risk of severe infections.

Optimal dose ofintravenous cyclophosphamide during remission induction therapy inANCA-associated vasculitis: A retrospective cohort study ofJ-CANVAS.

To identify the optimal dose of intravenous cyclophosphamide (IVCY) for induction therapy for anti-neutrophil cytoplasmic antibody-associated vasculitis. We retrospectively assessed patients with antibody-associated vasculitis who received IVCY every 2-3 weeks during the remission induction phase. The associations of the IVCY dose with infection-free survival and relapse-free survival were analysed using a Cox regression model. We compared patients in three categories: very low-dose (VLD), low-dose (LD), and conventional dose (CD) (<7.5 mg/kg, 7.5-12.5 mg/kg, and >12.5 mg/kg, respectively). The non-linear association between IVCY dose and the outcomes was also evaluated. Of the 80 patients (median age 72 years), 12, 42, and 26 underwent the VLD, LD, and CD regimens, respectively, of whom 4, 3, and 7 developed infection or died. The adjusted hazard ratios for infection or death were 4.3 (95% confidence interval (CI) 0.94-19.8) for VLD and 5.1 (95% CI 1.21-21.3) for CD, compared with LD. We found the hazard ratio for infection or death increased when the initial IVCY dose exceeded 9 mg/kg. Relapse-free survival did not differ clearly. Low-dose IVCY (7.5-12.5 mg/kg) may result in fewer infections and similar relapse rates compared with the conventional regimen (>12.5 mg/kg).