Cefazolin Prophylaxis for Total Joint Arthroplasty: Obese Patients Are Frequently Underdosed and at Increased Risk of Periprosthetic Joint Infection

Background One of the most effective prophylactic strategies against periprosthetic joint infection (PJI) is administration of perioperative antibiotics. Many orthopedic surgeons are unaware of the weight-based dosing protocol for cefazolin. This study aimed at elucidating what proportion of patients receiving cefazolin prophylaxis are underdosed and whether this increases the risk of PJI. Methods A retrospective study of 17,393 primary total joint arthroplasties receiving cefazolin as perioperative prophylaxis from 2005 to 2017 was performed. Patients were stratified into 2 groups (underdosed and adequately dosed) based on patient weight and antibiotic dosage. Patients who developed PJI within 1 year following index procedure were identified. A bivariate and multiple logistic regression analyses were performed to control for potential confounders and identify risk factors for PJI. Results The majority of patients weighing greater than 120 kg (95.9%, 944/984) were underdosed. Underdosed patients had a higher rate of PJI at 1 year compared with adequately dosed patients (1.51% vs 0.86%, P = .002). Patients weighing greater than 120 kg had higher 1-year PJI rate than patients weighing less than 120 kg (3.25% vs 0.83%, P < .001). Patients who were underdosed (odds ratio, 1.665; P = .006) with greater comorbidities (odds ratio, 1.259; P < .001) were more likely to develop PJI at 1 year. Conclusion Cefazolin underdosing is common, especially for patients weighing more than 120 kg. Our study reports that underdosed patients were more likely to develop PJI. Orthopedic surgeons should pay attention to the weight-based dosing of antibiotics in the perioperative period to avoid increasing risk of PJI

Mining and Analyzing the Italian Parliament: Party Structure and Evolution

The roll calls of the Italian Parliament in the XVI legislature are studied by employing multidimensional scaling, hierarchical clustering, and network analysis. In order to detect changes in voting behavior, the roll calls have been divided in seven periods of six months each. All the methods employed pointed out an increasing fragmentation of the political parties endorsing the previous government that culminated in its downfall. By using the concept of modularity at different resolution levels, we identify the community structure of Parliament and its evolution in each of the considered time periods. The analysis performed revealed as a valuable tool in detecting trends and drifts of Parliamentarians. It showed its effectiveness at identifying political parties and at providing insights on the temporal evolution of groups and their cohesiveness, without having at disposal any knowledge about political membership of Representatives.Comment: 27 pages, 14 figure

Surgical Treatment of Chronic Periprosthetic Joint Infection: Fate of Spacer Exchanges

Introduction Patients with periprosthetic joint infection (PJI) undergoing two-stage exchange arthroplasty may undergo an interim spacer exchange for a variety of reasons including mechanical failure of spacer or persistence of infection. The objective of this study was to understand the risk factors and outcomes of patients that undergo spacer exchange during the course of a planned two-stage exchange arthroplasty. Methods Our institutional database was used to identify 533 patients who underwent a two-stage exchange arthroplasty for PJI, including 90 patients with a spacer exchange, from 2000-2017. A retrospective review was performed to extract relevant clinical information. Treatment outcomes included 1) progression to reimplantation and 2) treatment success as defined by a Delphi-based criterion. Both univariate and multivariate COX regression models were performed to investigate whether spacer exchange was associated with failure. Additionally, a propensity score analysis was performed based on a 1:2 match. Results A spacer exchange was required in 16.9%. Patients who underwent spacer exchanges had a higher body mass index (BMI) (p<0.001), rheumatoid arthritis (p=0.018), and were more likely to have PJI caused by resistant (0.048) and polymicrobial organisms (p=0.007). Patients undergoing a spacer exchange demonstrated lower survivorship and an increased risk of failure in the multivariate and propensity score matched analysis compared to patients who did not require a spacer exchange. Discussion Despite an additional load of local antibiotics and repeat debridement, patients who underwent a spacer exchange demonstrated poor outcomes, including failure to undergo reimplantation and twice the failure rate. The findings of this study may need to be borne in mind when managing patients who require spacer exchange

A gut-to-brain signal of fluid osmolarity controls thirst satiation.

Satiation is the process by which eating and drinking reduce appetite. For thirst, oropharyngeal cues have a critical role in driving satiation by reporting to the brain the volume of fluid that has been ingested1-12. By contrast, the mechanisms that relay the osmolarity of ingested fluids remain poorly understood. Here we show that the water and salt content of the gastrointestinal tract are precisely measured and then rapidly communicated to the brain to control drinking behaviour in mice. We demonstrate that this osmosensory signal is necessary and sufficient for satiation during normal drinking, involves the vagus nerve and is transmitted to key forebrain neurons that control thirst and vasopressin secretion. Using microendoscopic imaging, we show that individual neurons compute homeostatic need by integrating this gastrointestinal osmosensory information with oropharyngeal and blood-borne signals. These findings reveal how the fluid homeostasis system monitors the osmolarity of ingested fluids to dynamically control drinking behaviour

SnTox3 Acts in Effector Triggered Susceptibility to Induce Disease on Wheat Carrying the Snn3 Gene

The necrotrophic fungus Stagonospora nodorum produces multiple proteinaceous host-selective toxins (HSTs) which act in effector triggered susceptibility. Here, we report the molecular cloning and functional characterization of the SnTox3-encoding gene, designated SnTox3, as well as the initial characterization of the SnTox3 protein. SnTox3 is a 693 bp intron-free gene with little obvious homology to other known genes. The predicted immature SnTox3 protein is 25.8 kDa in size. A 20 amino acid signal sequence as well as a possible pro sequence are predicted. Six cysteine residues are predicted to form disulfide bonds and are shown to be important for SnTox3 activity. Using heterologous expression in Pichia pastoris and transformation into an avirulent S. nodorum isolate, we show that SnTox3 encodes the SnTox3 protein and that SnTox3 interacts with the wheat susceptibility gene Snn3. In addition, the avirulent S. nodorum isolate transformed with SnTox3 was virulent on host lines expressing the Snn3 gene. SnTox3-disrupted mutants were deficient in the production of SnTox3 and avirulent on the Snn3 differential wheat line BG220. An analysis of genetic diversity revealed that SnTox3 is present in 60.1% of a worldwide collection of 923 isolates and occurs as eleven nucleotide haplotypes resulting in four amino acid haplotypes. The cloning of SnTox3 provides a fundamental tool for the investigation of the S. nodorum-wheat interaction, as well as vital information for the general characterization of necrotroph-plant interactions.This work was supported by USDA-ARS CRIS projects 5442-22000-043-00D and 5442-22000-030-00D

H2AX Deficiency is Associated with Erythroid Dysplasia and Compromised Haematopoietic Stem Cell Function

Myelodysplastic syndromes (MDS) are clonal disorders of haematopoiesis characterised by dysplastic changes of major myeloid cell lines. However, the mechanisms underlying these dysplastic changes are poorly understood. Here, we used a genetically modified mouse model and human patient data to examine the physiological roles of H2AX in haematopoiesis and how the loss of H2AX contributes to dyserythropoiesis in MDS. H2AX knockout mice showed cell-autonomous anaemia and erythroid dysplasia, mimicking dyserythropoiesis in MDS. Also, dyserythropoiesis was increased in MDS patients with the deletion of chromosome 11q23, where H2AX is located. Although loss of H2AX did not affect the early stage of terminal erythropoiesis, enucleation was decreased. H2AX deficiency also led to the loss of quiescence of hematopoietic stem and progenitor cells, which dramatically compromised their bone marrow engraftment. These results reveal important roles of H2AX in late-stage terminal erythropoiesis and hematopoietic stem cell function

Association of Laminar Airflow During Primary Total Joint Arthroplasty With Periprosthetic Joint Infection.

Importance: Whether laminar airflow (LAF) in the operating room is effective for decreasing periprosthetic joint infection (PJI) after total joint arthroplasty remains a clinically important yet controversial issue. Objective: To investigate the association between operating room LAF ventilation systems and the risk of PJI in patients undergoing total joint arthroplasty. Design, Setting, and Participants: A retrospective cohort study was conducted of 6972 consecutive patients undergoing primary total knee arthroplasty or total hip arthroplasty at 2 surgical facilities within a single institution from January 1, 2013, to September 15, 2017, with a minimum of 1 year of follow-up. All procedures were performed by 5 board-certified arthroplasty surgeons. Statistical analysis was performed from January 1, 2014, to September 15, 2018. Exposure: Patients underwent total joint arthroplasty in operating rooms equipped with either LAF or turbulent airflow. Main Outcomes and Measures: Patient characteristics were extracted from clinical records. Periprosthetic joint infection was defined according to Musculoskeletal Infection Society criteria within 1 year of the index arthroplasty. A multivariable logistic regression model was performed to explore the potential association between LAF and risk of PJI at 1 year, and then a sensitivity analysis using propensity score matching was performed to further validate the findings. Results: A total of 6972 patients (2797 who underwent total knee arthroplasty and 4175 who underwent total hip arthroplasty; 3690 women [52.9%]; mean [SD] age, 63.9 [10.7] years) were included. The incidence of PJI within 1 year for patients from the facility without LAF was similar to that of patients from the facility with LAF (0.4% [12 of 3027] vs 0.5% [21 of 3945]). In the multivariable logistic regression analysis, after all confounding factors were taken into account, the use of LAF was not associated with a reduction of the risk of PJI (adjusted odds ratio, 0.94; 95% CI, 0.40-2.19; P = .89). After propensity score matching, there was no significant difference in the incidence of PJI within 1 year for patients who underwent total joint arthroplasty at these 2 sites. Conclusions and Relevance: This study suggests that the use of LAF in the operating room was not associated with a reduced incidence of PJI after primary total joint arthroplasty. With an appropriate perioperative protocol for infection prevention, LAF does not seem to play a protective role in PJI prevention

mRNA processing in mutant zebrafish lines generated by chemical and CRISPR-mediated mutagenesis produces unexpected transcripts that escape nonsense-mediated decay.

As model organism-based research shifts from forward to reverse genetics approaches, largely due to the ease of genome editing technology, a low frequency of abnormal phenotypes is being observed in lines with mutations predicted to lead to deleterious effects on the encoded protein. In zebrafish, this low frequency is in part explained by compensation by genes of redundant or similar function, often resulting from the additional round of teleost-specific whole genome duplication within vertebrates. Here we offer additional explanations for the low frequency of mutant phenotypes. We analyzed mRNA processing in seven zebrafish lines with mutations expected to disrupt gene function, generated by CRISPR/Cas9 or ENU mutagenesis methods. Five of the seven lines showed evidence of altered mRNA processing: one through a skipped exon that did not lead to a frame shift, one through nonsense-associated splicing that did not lead to a frame shift, and three through the use of cryptic splice sites. These results highlight the need for a methodical analysis of the mRNA produced in mutant lines before making conclusions or embarking on studies that assume loss of function as a result of a given genomic change. Furthermore, recognition of the types of adaptations that can occur may inform the strategies of mutant generation

The Fate of Periprosthetic Joint Infection Following Megaprosthesis Reconstruction

Background: A megaprosthesis may be used for reconstruction in patients with massive bone loss or a periprosthetic fracture. Periprosthetic joint infection (PJI) may occur after a megaprosthesis reconstruction and may pose a major challenge. The outcomes of managing PJI in patients with a megaprosthesis is relatively unclear. The aim of this study was to investigate the clinical course and outcomes of PJI in patients with a megaprosthesis in place. Methods: From a total of 219 patients who underwent megaprosthesis replacement for non-oncologic conditions, 38 (17.4%) developed subsequent PJI. A retrospective review of the medical record was performed to ascertain the course of the PJI and treatment outcomes. Kaplan-Meier analysis was performed to evaluate the survival function, and the log-rank test was used to assess differences in outcome measures. Results: The surgical management of 33 patients with PJI included debridement, antibiotics, and implant retention (DAIR) (82%), consisting of DAIR with modular component exchange (19 patients) and DAIR without component exchange (8 patients); 2-stage exchange arthroplasty (9%); resection arthroplasty (6%); and a single-stage revision arthroplasty (3%). The Kaplan-Meier survivorship analysis demonstrated that the overall survival rate was 65.1% at 2 years. The mortality rate was 15%, with many patients undergoing salvage procedures including amputation (18%), arthrodesis (6%), and resection arthroplasty (6%). Conclusions: The rate of PJI after megaprosthesis reconstruction, 17% in this study, appears to be very high. The management of PJI in these patients is challenging, with 1 of 3 patients undergoing failed treatment. Despite the limited options available, DAIR seems to be an appropriate treatment strategy for some of these patients. Further data on a larger cohort are needed to assess the success of various surgical procedures and predictors of failure in this challenging patient population. Level of evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence

Isolation Precautions for Visitors

Transmission of organisms within the hospital setting has become a topic of major concern not only for patients and healthcare facilities but also for government agencies and the general public. This increased awareness has occurred in part due to the spread of organisms that have limited treatment options, such as carbapenem-resistant Enterobacteriaceae (CRE), as well as the heightened recognition that many hospital-associated infections (HAIs) are preventable. A large body of literature shows that horizontal transmission of multidrug-resistant organisms involves the hands, and potentially the attire, of healthcare workers (HCWs). This evidence provides the rationale for the use of standard and contact isolation precautions among HCWs. However, the health risks to visitors and the role of visitors in the horizontal transmission of pathogens within acute care hospitals is not as clearly defined. Consequently, uncertainty remains regarding which precautions visitors should take when interacting with patients placed on isolation precautions. Frequent arguments against the use of isolation precautions among visitors include lack of visitor movement between patient rooms, the difficulty of educating visitors, and the difficulty of enforcing compliance with isolation practices