Early Versus Late Periprosthetic Joint Infection After Total Knee Arthroplasty: Do Patient Differences Exist?

BACKGROUND: Periprosthetic joint infection (PJI) is a devastating complication following total knee arthroplasty (TKA). Little evidence exists comparing those with early versus late PJI. The purpose of the study was to determine comorbidity profile differences between patients developing early and late PJI. METHODS: There were 72,659 patients undergoing primary TKA from 2009 to 2021, who were identified from a commercial claims and encounters database. Subjects diagnosed with PJI were categorized as either 'early' (within 90 days of index procedure) or 'late' (> 2 years after index arthroplasty). Non-infected patients within these periods served as control groups following 4:1 propensity score matching on other extraneous variables. Logistic regression analyses were performed comparing comorbidities between groups. RESULTS: Patients were significantly younger in the late compared to the early infection group (58.1 versus 62.4 years, P < .001). When compared to those with early PJI, patients who had chronic kidney disease (13.3 versus 4.1%; OR [odds ratio] 5.17, P = .002), malignancy (20.4 versus 10.5%; OR 2.53, P = .009), uncomplicated diabetes (40.8 versus 30.6%; OR 2.00, P = .01), rheumatoid arthritis (9.2 versus 3.3%; OR 2.66, P = .046), and hypertension (88.8 versus 81.6%; OR 2.17, P = .04), were all significant predictors of developing a late PJI. CONCLUSIONS: When compared to patients diagnosed with early PJI following primary TKA, the presence of chronic kidney disease, malignancy, uncomplicated diabetes, rheumatoid arthritis, and hypertension, were independent risk factors for the development of late PJI. Younger patients who have these comorbidities may be targets for preoperative optimization interventions that minimize the risk of PJI.

Preoperative Risk Factor Analysis and Dynamic Online Nomogram Development for Early Infections Following Primary Hip Arthroplasty in Geriatric Patients with Hip Fracture.

Background: Hip arthroplasty is in increasing demand with the aging of the world population, and early infections, such as pneumonia, surgical site infection (SSI), and urinary tract infection (UTI), are uncommon but fatal complications following hip arthroplasty. This study aimed to identify preoperative risk factors independently associated with early infections following primary arthroplasty in geriatric hip fracture patients, and to develop a prediction nomogram. Methods: Univariate and multivariate logistical analyses were performed to identify the independent risk factors for early infections, which were combined and transformed into a nomogram model. The prediction model was evaluated by using the area under the receiver operating characteristic curve (AUC), Hosmer-Lemeshow test, concordance index (C-index), 1000 bootstrap replications, decision curve analysis (DCA), and calibration curve. Results: One thousand eighty-four eligible patients got included and 7 preoperative variables were identified to be independently associated with early infections, including heart disease (odds ratio (OR): 2.17; P: 0.026), cerebrovascular disease (OR: 2.25; P: 0.019), liver disease (OR: 8.99; P: <0.001), time to surgery (OR: 1.10; P: 0.012), hematocrit (44.52; OR: 2.73; P: 0.047), and high-sensitivity C-reactive protein (HCRP; >78.64mg/L; OR: 3.71; P: <0.001). For the nomogram model, AUC was 0.807 (95% confidence interval (CI): 0.742-0.873), the Hosmer-Lemeshow test demonstrated no overfitting (P = 0.522), and C-index was 0.807 (95% CI: 0.742-0.872) with corrected value of 0.784 after 1000 bootstrapping validations. Moreover, the calibration curve and DCA exhibited the tools' good prediction consistency and clinical practicability. Conclusion: Heart disease, cerebrovascular disease, liver disease, time to surgery, hematocrit, PMR, and HCRP were significant preoperative predictors for early infections following primary arthroplasty in elderly hip fracture patients, and the converted nomogram model had strong discriminatory ability and translatability to clinical application.

Effect of Carbapenem-Resistant Klebsiella pneumoniae Infection on the Clinical Outcomes of Kidney Transplant Recipients.

Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) infection has proven to be difficult to control and typically presents with devastating effects. Methods: This retrospective study was conducted on the renal recipients at our institution between January 2021 to January 2022. Clinical data was collected to identify factors associated with CRKP infection and clinical outcomes. Results: There were 104 cases out of 186 total renal recipients who presented with at least one infection within 3 months after KT, and 14 cases developed unfavorable clinical outcomes. We identified 16 confirmed CRKP infected cases with the incidence of 8.60%. Possible donor derived infection (DDI) (OR = 6.743; 95% CI: 1.477-30.786; P = 0.014) were independent risk factors for the occurrence of CRKP infection of renal recipients in our analysis, CRKP infection (OR = 20.723; 95% CI: 3.448-124.547; P = 0.001) and pneumonia (OR = 28.458; 95% CI: 1.956-413.984 P = 0.014) were independent risk factors for the occurrence of unfavorable clinical outcomes following KT, and the occurrence of unfavorable clinical outcomes following KT were significantly associated with CRKP infection (r = 0.535; P < 0.001) and antibiotic regimen containing ceftazidime/avibactam (CZA) (r = -0.655; P = 0.006). The use of CZA was significantly different in the comparison of antibiotic regimens between the CRKP infected renal recipients with unfavorable outcomes and CRKP infected patients with favorable outcomes. Conclusion: It is possible that DDI can lead to CRKP infection, and CRKP infection and pneumonia were closely correlated with poor prognosis. The use of CZA may play a role in avoiding the unfavorable outcomes of CRKP infected recipients.

Infections in the first year of life and development of beta cell autoimmunity and clinical type 1 diabetes in high-risk individuals: the TRIGR cohort.

AIMS/HYPOTHESIS: Accumulated data suggest that infections in early life contribute to the development of type 1 diabetes. Using data from the Trial to Reduce IDDM in the Genetically at Risk (TRIGR), we set out to assess whether children who later developed diabetes-related autoantibodies and/or clinical type 1 diabetes had different exposure to infections early in life compared with those who did not. METHODS: A cohort of 2159 children with an affected first-degree relative and HLA-conferred susceptibility to type 1 diabetes were recruited between 2002 and 2007 and followed until 2017. Infections were registered prospectively. The relationship between infections in the first year of life and the development of autoantibodies or clinical type 1 diabetes was analysed using univariable and multivariable Cox regression models. As this study was exploratory, no adjustment was made for multiple comparisons. RESULTS: Adjusting for HLA, sex, breastfeeding duration and birth order, those who had seven or more infections during their first year of life were more likely to develop at least one positive type 1 diabetes-related autoantibody (p=0.028, HR 9.166 [95% CI 1.277, 65.81]) compared with those who had no infections. Those who had their first viral infection aged between 6 and 12 months were less likely to develop at least one positive type 1 diabetes-related antibody (p=0.043, HR 0.828 [95% CI 0.690, 0.994]) or multiple antibodies (p=0.0351, HR 0.664 [95% CI 0.453, 0.972]). Those who had ever had an unspecified bacterial infection were more likely to develop at least one positive type 1 diabetes-related autoantibody (p=0.013, HR 1.412 [95% CI 1.075, 1.854]), to develop multiple antibodies (p=0.037, HR 1.652 [95% CI 1.030, 2.649]) and to develop clinical type 1 diabetes (p=0.011, HR 2.066 [95% CI 1.182, 3.613]). CONCLUSIONS/INTERPRETATION: We found weak support for the assumption that viral infections early in life may initiate the autoimmune process or later development of type 1 diabetes. In contrast, certain bacterial infections appeared to increase the risk of both multiple autoantibodies and clinical type 1 diabetes.

Analysis of Risk Factors for Carbapenem-Resistant Klebsiella pneumoniae Infection and Its Effect on the Outcome of Early Infection After Kidney Transplantation.

Background: Infections remain a major cause of morbidity and mortality in kidney transplant (KT) recipients. This study was performed to identify the overall prevalence of early infections, prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKP) infection after KT, one-year postoperative mortality in patients with early infections and risk factors for CRKP infections. Methods: We conducted a retrospective study of all patients who received KT in our hospital between January 2017 and December 2019. We evaluated the demographic, clinical, infection characteristics and the one-year postoperative outcomes. Results: Among the 419 patients who received KT between January 2017 and December 2019, 150 patients had at least one infection within 90 days after KT. The total prevalence of early infections was 36.1% (150/415), the prevalence of early CRKP infections was 10.4% (43/415), and the one-year postoperative mortality was 15.3% (23/150) in patients with early infections. The risk factors independently related to one-year postoperative mortality were mechanical ventilation (MV) > 48 h (Odds ratio (OR)= 13.879, 95%Confidence interval (CI): 2.265~85.035; P=0.004) and CRKP infection (OR=6.751, 95% CI: 1.051~43.369; P =0.044). MV> 48 h was independently related to CRKP infection (OR=3.719, 95% CI: 1.024~13.504; P=0.046). Kaplan-Meier survival curves showed that the one-year survival rate of patients infected with CRKP in the early postoperative stage was significantly lower than that of uninfected patients. Conclusions: In general, the prevalence of early infections after KT is high, and CRKP infection is closely correlated with poor prognosis. The effective prevention and treatment of CRKP infection is an important way to improve the one-year survival rate after KT.

Subtype-specific differences in transmission cluster dynamics of HIV-1 B and CRF01_AE in New South Wales, Australia.

INTRODUCTION: The human immunodeficiency virus 1 (HIV-1) pandemic is characterized by numerous distinct sub-epidemics (clusters) that continually fuel local transmission. The aims of this study were to identify active growing clusters, to understand which factors most influence the transmission dynamics, how these vary between different subtypes and how this information might contribute to effective public health responses. METHODS: We used HIV-1 genomic sequence data linked to demographic factors that accounted for approximately 70% of all new HIV-1 notifications in New South Wales (NSW). We assessed differences in transmission cluster dynamics between subtype B and circulating recombinant form 01_AE (CRF01_AE). Separate phylogenetic trees were estimated using 2919 subtype B and 473 CRF01_AE sequences sampled between 2004 and 2018 in combination with global sequence data and NSW-specific clades were classified as clusters, pairs or singletons. Significant differences in demographics between subtypes were assessed with Chi-Square statistics. RESULTS: We identified 104 subtype B and 11 CRF01_AE growing clusters containing a maximum of 29 and 11 sequences for subtype B and CRF01_AE respectively. We observed a > 2-fold increase in the number of NSW-specific CRF01_AE clades over time. Subtype B clusters were associated with individuals reporting men who have sex with men (MSM) as their transmission risk factor, being born in Australia, and being diagnosed during the early stage of infection (p < 0.01). CRF01_AE infections clusters were associated with infections among individuals diagnosed during the early stage of infection (p < 0.05) and CRF01_AE singletons were more likely to be from infections among individuals reporting heterosexual transmission (p < 0.05). We found six subtype B clusters with an above-average growth rate (>1.5 sequences / 6-months) and which consisted of a majority of infections among MSM. We also found four active growing CRF01_AE clusters containing only infections among MSM. Finally, we found 47 subtype B and seven CRF01_AE clusters that contained a large gap in time (>1 year) between infections and may be indicative of intermediate transmissions via undiagnosed individuals. CONCLUSIONS: The large number of active and growing clusters among MSM are the driving force of the ongoing epidemic in NSW for subtype B and CRF01_AE.

HIV-1 subtype C predicted co-receptor tropism in Africa: an individual sequence level meta-analysis.

BACKGROUND: Entry inhibitors, such as Maraviroc, hold promise as components of HIV treatment and/or pre-exposure prophylaxis in Africa. Maraviroc inhibits the interaction between HIV Envelope gp120 V3-loop and CCR5 coreceptor. HIV-1 subtype C (HIV-1-C) is predominant in Southern Africa and preferably uses CCR5 co-receptor. Therefore, a significant proportion of HIV-1-C CXCR4 utilizing viruses (X4) may compromise the effectiveness of Maraviroc. This analysis examined coreceptor preferences in early and chronic HIV-1-C infections across Africa. METHODS: African HIV-1-C Envelope gp120 V3-loop sequences sampled from 1988 to 2014 were retrieved from Los Alamos HIV Sequence Database. Sequences from early infections (< 186 days post infection) and chronic infections (> 186 days post infection) were analysed for predicted co-receptor preferences using Geno2Pheno [Coreceptor] 10% FPR, Phenoseq-C, and PSSMsinsi web tools. V3-loop diversity was determined, and viral subtype was confirmed by phylogenetic analysis. National treatment guidelines across Africa were reviewed for Maraviroc recommendation. RESULTS: Sequences from early (n = 6316) and chronic (n = 7338) HIV-1-C infected individuals from 10 and 15 African countries respectively were available for analyses. Overall, 518/6316 (8.2%; 95% CI 0.7-9.3) of early sequences were X4, with Ethiopia and Malawi having more than 10% each. For chronic infections, 8.3% (95% CI 2.4-16.2) sequences were X4 viruses, with Ethiopia, Tanzania, and Zimbabwe having more than 10% each. For sequences from early chronic infections (< 1 year post infection), the prevalence of X4 viruses was 8.5% (95% CI 2.6-11.2). In late chronic infections (≥ 5 years post infection), X4 viruses were observed in 36% (95% CI - 16.3 to 49.9), with two countries having relatively high X4 viruses: South Africa (43%) and Malawi (24%). The V3-loop amino acid sequence were more variable in X4 viruses in chronic infections compared to acute infections, with South Africa, Ethiopia and Zimbabwe showing the highest levels of V3-loop diversity. All sequences were phylogenetically confirmed as HIV-1-C and clustered according to their co-receptor tropism. In Africa, Maraviroc is registered only in South Africa and Uganda. CONCLUSIONS: Our analyses illustrate that X4 viruses are present in significantly similar proportions in early and early chronic HIV-1 subtype C infected individuals across Africa. In contrast, in late chronic infections, X4 viruses increase 3-5 folds. We can draw two inferences from our observations: (1) to enhance the utility of Maraviroc in chronic HIV subtype C infections in Africa, prior virus co-receptor determination is needed; (2) on the flip side, research on the efficacy of CXCR4 antagonists for HIV-1-C infections is encouraged. Currently, the use of Maraviroc is very limited in Africa.

The role of the early social environment on Epstein Barr virus infection: a prospective observational design using the Millennium Cohort Study.

Epstein-Barr virus (EBV) is a highly prevalent herpesvirus linked to infectious mononucleosis and several malignancies. This paper aims to study the association between children's early life social environment at 9 months and EBV infection at 3 years of age. METHODS: We used data on children included in the UK Millennium Cohort Study. We described the social environment using area-level and material factors as well as socioeconomic position (SEP) at 9 months. EBV was measured at 3 years of age (n = 12 457). RESULTS: Lower rates of EBV infection were observed in children living in towns and rural areas compared with those living in cities. Lower SEP and overcrowding in the household increased the odds of being infected. Children whose parents were social tenants were more likely to be infected than homeowners. In the overall model, the strength of the association between material factors and EBV infection weakened. CONCLUSIONS: We showed that early life material deprivation was associated with a higher risk of EBV infection among 3-year-olds. Children living in more deprived social conditions may be more likely to become EBV carriers at an earlier age.

Carbapenem-Resistant Klebsiella pneumoniae influences the outcome of early infections in liver transplant recipients.

BACKGROUND: Infections remain a leading cause of morbidity and mortality among liver transplant (LT) recipients. The aim of our study was to define the factors associated with outcome of early bacterial and fungal infections in a cohort of patients who underwent LT at the University Hospital of Ancona over a nine year period. METHODS: All consecutive patients who underwent LT in our center were considered. An early infection was defined as occurring in the first month post-transplantation. RESULTS: Among 330 patients who underwent LT from August 2005 to October 2014, 88 (27 %) had at least one infection documented within 30 days after transplantation. In 54 cases only one site was involved, in 34 cases ≥2 sites. There were 43 (30 %) pneumonia, 40 (27 %) surgical site infections, 31 (22 %) blood stream infections, and 30 (21 %) urinary tract infections. Gram-negative bacteria accounted for 64 % of the culture-positive cases, followed by Gram-positive bacteria (30 %) and fungi (6 %). A high proportion of drug-resistant strains was found within either Gram-negative (79 %) or Gram-positive (81 %) bacteria. There were 27 out 88 patients (31 %) who died within 180 days from the transplant. Factors independently associated with a higher risk of mortality were: renal replacement therapy (HR 11.797 [CI95 % 3.082-45.152], p < 0.0001), multisite infections (HR 4.865 [CI95 % 1.417-16.700], p = 0.012) and being infected with carbapenem-resistant Klebsiella pneumoniae (CRKP; HR 5.562 [CI95 % 1.186-26.088], p = 0.030). CONCLUSIONS: Overall, these data indicate that early infections in LT patients are characterized by significant mortality. In particular, an early infection caused by CRKP has an adverse impact on survival in these patients suggesting an urgent need for adopting preventive measures to avoiding this complication.

Exploring the risk factors for differences in the cumulative incidence of coeliac disease in two neighboring countries: the prospective DIABIMMUNE study.

BACKGROUND: During the last several decades the prevalence of coeliac disease (CD) has increased worldwide. AIM: To compare the cumulative incidence of CD between Estonian and Finnish children and to identify the risk factors. MATERIALS AND METHODS: Children were recruited as part of the DIABIMMUNE Study. In the birth cohort (BC) 258 children from Estonia and 305 from Finland, and in the young children's cohort (YCC) 1363 and 1384 children were followed up, respectively. The diagnosis of CD was made in accordance with the ESPGHAN guidelines-the presence of IgA-tTG antibodies and small bowel villous atrophy. RESULTS: During the study period 29 children developed CD. The cumulative incidence of CD was significantly higher in Finland (0.77% vs 0.27%; P=0.01). No difference was seen between the children with CD and the controls in the duration of breastfeeding or the age at cereal introduction. The BC children with CD had had significantly more episodes of infections with fever by the age of 12 months compared to the controls (3.4 vs 1.4; P=0.04). CONCLUSION: The 5-year cumulative incidence of childhood CD is significantly higher in Finland than in Estonia. Sequential infections early in life may increase the risk for developing CD.