Periprosthetic Joint Infection: What's New?

Total joint arthroplasty (TJA) ranks among the most commonly performed orthopedic surgeries, with its annual incidence on the rise globally. Periprosthetic joint infection (PJI) remains a leading cause of arthroplasty failure. This review aims to summarize recent literature updates on the epidemiology, diagnosis, and management of PJI.

Adverse Events in Osimertinib Treatment for EGFR-Mutated Non-Small-Cell Lung Cancer: Unveiling Rare Life-Threatening Myelosuppression.

Recent advancements in targeted therapies for non-small-cell lung cancer (NSCLC), specifically focusing on epidermal growth factor receptor (EGFR) mutations, have revolutionized treatment strategies. Osimertinib, an approved therapy for metastatic NSCLC with EGFR mutations, highlights remarkable efficacy but also harbors the potential for severe adverse events, whose rarity or lack of precedence may mask their criticality. This article delves into the exploration of adverse events linked to osimertinib, shedding light on a rare yet life-threatening occurrence: severe myelosuppression. A case study detailing a patient with EGFR-mutated NSCLC exhibiting a robust treatment response but experiencing severe myelosuppression following osimertinib initiation is presented. Immediate discontinuation of osimertinib alongside concurrent blood transfusions facilitated toxicity recovery, prompting a successful reduction in myelosuppression severity upon re-administration at a lowered dosage.

The Efficacy of Cannabis in Oncology Patient Care and Its Anti-Tumor Effects.

As the legalization of medical cannabis expands across several countries, interest in its potential advantages among cancer patients and caregivers is burgeoning. However, patients seeking to integrate cannabis into their treatment often encounter frustration when their oncologists lack adequate information to offer guidance. This knowledge gap is exacerbated by the scarcity of published literature on the benefits of medical cannabis, leaving oncologists reliant on evidence-based data disheartened. This comprehensive narrative article, tailored for both clinicians and patients, endeavors to bridge these informational voids. It synthesizes cannabis history, pharmacology, and physiology and focuses on addressing various symptoms prevalent in cancer care, including insomnia, nausea and vomiting, appetite issues, pain management, and potential anti-cancer effects. Furthermore, by delving into the potential mechanisms of action and exploring their relevance in cancer treatment, this article aims to shed light on the potential benefits and effects of cannabis in oncology.

Multimodal Imaging in Mycobacterium Chimaera Cardiovascular Infections: The Mayo Clinic Experience.

Objective: To review the salient features of multimodality cardiovascular imaging in patients with disseminated Mycobacterium chimaera (MC) infections after exposure to contaminated heater-cooler units during cardiopulmonary bypass. Patients and Methods: Twelve patients with confirmed MC infection were retrospectively identified after a review from January 1, 2010, to April 30, 2021. The electronic medical records were examined with a focus on transthoracic echocardiography, transesophageal echocardiography, cardiac computed tomography (CT), cardiac magnetic resonance imaging, and positron emission tomography-CT. Results: Three (27.3%) patients had diagnostic findings of endocarditis on transthoracic echocardiography, with most patients having nonspecific abnormalities including elevated prosthetic valve gradients or prosthetic leaflet thickening. Transesophageal echocardiography identified 4 (36.7%) patients with vegetations and 3 (27.3%) with aortic root abscess or pseudoaneurysm, with more common findings such as mild aortic root or prosthetic leaflet thickening. Six (50%) patients underwent cardiac CT imaging, which found aortic root pseudoaneurysms or abscesses, prosthetic ring dehiscence, and leaflet thickening. Three (25%) patients underwent cardiac magnetic resonance imaging demonstrating prosthetic valve vegetations, leaflet thickening, and abnormal myocardial delayed enhancement in a noncoronary distribution, suggesting myocarditis. Ten (83%) patients underwent positron emission tomography-CT, 4 (40%) had an abnormal fluorodeoxyglucose uptake around the cardiac prosthetic material, and 7 (70%) had a fluorodeoxyglucose uptake in other organs, suggesting concomitant multiorgan involvement. Conclusion: Multimodality cardiovascular imaging is central to the management of patients with disseminated MC and can help establish a preliminary diagnosis while awaiting confirmatory microbiological data, potentially reducing the time to diagnosis. Imaging findings are subtle and atypical, not always meeting classically modified Duke's criteria for infectious endocarditis. Clinicians should have a high index of suspicion for the disease and a low threshold for repeat imaging when initial testing is equivocal.

Effect of Antibiotic Therapy Before Arthrocentesis on Synovial Fluid Cell Count and Differential for Diagnosis of Native Joint Septic Arthritis.

We examined the effect of preoperative antibiotic exposure and duration on synovial fluid samples from patients with native joint septic arthritis of the hip/knee. While exposure before diagnostic arthrocentesis did not affect fluid parameters, increased duration was associated with a decreased total nucleated cell count, underscoring the complex antibiotic effects on synovial fluid parameters.

Graft versus histoplasma disease: A case of vascular graft infection.

Histoplasma vascular graft infection (VGI) is rarely reported, with only a handful of instances documented in the existing literature. Reporting Histoplasma VGI cases is important as they demonstrate previous treatment strategies and their outcomes. In this paper, we report a case of disseminated histoplasmosis with ascending aortic graft infection. Conservative therapy was attempted initially but failed, and our patient eventually required surgical graft explantation. Our case demonstrates the challenges in diagnosing and managing VGI caused by Histoplasma capsulatum.

Advanced and Metastatic Non-Melanoma Skin Cancer: Epidemiology, Risk Factors, Clinical Features, and Treatment Options.

Non-melanoma skin cancers (NMSC) form the majority of skin cancers, with basal cell carcinoma (BCC) being the most common and cutaneous squamous cell carcinoma (cSCC) being second. Prolonged ultraviolet (UV) exposure, aging, male gender, and immunosuppression represent most of the causes of this category of diseases. BCCs and cSCCs both include different types of skin cancers, such as nodular or morpheaform BCC or flat cSCC. Locally advanced and metastatic NMSCs cannot be treated surgically; thus, systemic therapy (TKI and Immunotherapy) is needed. Interestingly, NMSCs are frequently linked to abnormal Hedgehog (HH) signaling which most systemic immunotherapies for these cancers are based upon. Of note, the first line therapies of BCC, sonidegib and vismodegib, are HH inhibitors. Programmed death receptor 1 antibody (PD-1) inhibitors such as cemiplimab, pembrolizumab, and nivolumab have been approved for the treatment of cSCC. Thus, this paper reviews the epidemiology, risk factors, clinical features, and treatment options for both BCC and cSCC.

Use of the DMAIC Lean Six Sigma quality improvement framework to improve beta-lactam antibiotic adequacy in the critically ill.

Beta-lactam antibiotics are widely used in the intensive care unit due to their favorable effectiveness and safety profiles. Beta-lactams given to patients with sepsis must be delivered as soon as possible after infection recognition (early), treat the suspected organism (appropriate), and be administered at a dose that eradicates the infection (adequate). Early and appropriate antibiotic delivery occurs in >90% of patients, but less than half of patients with sepsis achieve adequate antibiotic exposure. This project aimed to address this quality gap and improve beta-lactam adequacy using the Define, Measure, Analyze, Improve, and Control Lean Six Sigma quality improvement framework. A multidisciplinary steering committee was formed, which completed a stakeholder analysis to define the gap in practice. An Ishikawa cause and effect (Fishbone) diagram was used to identify the root causes and an impact/effort grid facilitated prioritization of interventions. An intervention that included bundled education with the use of therapeutic drug monitoring (TDM; i.e. drug-level testing) was projected to have the highest impact relative to the amount of effort and selected to address beta-lactam inadequacy in the critically ill. The education and TDM intervention were deployed through a Plan, Do, Study, Act cycle. In the 3 months after "go-live," 54 episodes of beta-lactam TDM occurred in 41 unique intensive care unit patients. The primary quality metric of beta-lactam adequacy was achieved in 94% of individuals after the intervention. Ninety-four percent of clinicians gauged the education provided as sufficient. The primary counterbalance of antimicrobial days of therapy, a core antimicrobial stewardship metric, was unchanged over time (favorable result; P = .73). Application of the Define, Measure, Analyze, Improve, and Control Lean Six Sigma quality improvement framework effectively improved beta-lactam adequacy in critically ill patients. The approach taken in this quality improvement project is widely generalizable to other drugs, drug classes, or settings to increase the adequacy of drug exposure.

Plasma Microbial Cell-free DNA Next-generation Sequencing Can Be a Useful Diagnostic Tool in Patients With Osteoarticular Infections.

Background: Recent advances in shotgun metagenomic sequencing (sMGS) for detecting microbial cell-free DNA (mcfDNA) in peripheral blood have shown promise across various patient populations. This study evaluates the application of sMGS for diagnosing osteoarticular infections (OAIs), a condition with significant diagnostic challenges. Methods: We conducted a retrospective analysis on 73 patients suspected of OAIs at the Mayo Clinic from 2019 to 2023, incorporating mcfDNA sMGS (Karius test [KT]) into their diagnostic evaluation. We categorized the clinical impact of KT on OAI diagnoses and management into 4 distinct outcomes. (1) KT was able to confirm an established diagnosis, (2) KT supported noninfectious diseases diagnosis, (3) KT established an unsuspected diagnosis, (4) KT did not add relevant information. Results: In our cohort, KT was performed in 73 patients. Among the infected individuals, KT yielded positive results in 22 of 43 (51.2%) cases. Of these 22 cases, 11 (50%) showed agreement with conventional diagnostic workup, whereas in 5 (22.7%) cases, the KT established an unsuspected diagnosis. Native vertebral osteomyelitis diagnosis (P < .001) or OAIs with concomitant presence of endocarditis or endovascular infection (P = .005) were statistically associated with a definite, probable, or possible diagnostic certainty of KT result. Conclusions: In complex OAIs, KT enhanced diagnostic accuracy by 11.6%, proving especially beneficial in diagnosing native vertebral osteomyelitis and infections with concurrent endocarditis or endovascular complications. Our findings underscore the utility of KT in the diagnostic workflow for challenging OAI cases, potentially altering clinical management for a significant subset of patients.

Melanoma Management: Exploring Staging, Prognosis, and Treatment Innovations.

Melanoma, a malignant neoplasm originating from melanocytes, stands as one of the most prevalent cancers globally, ranking fifth in terms of estimated new cases in recent years. Its aggressive nature and propensity for metastasis pose significant challenges in oncology. Recent advancements have led to a notable shift towards targeted therapies, driven by a deeper understanding of cutaneous tumor pathogenesis. Immunotherapy and tyrosine kinase inhibitors have emerged as promising strategies, demonstrating the potential to improve clinical outcomes across all disease stages, including neoadjuvant, adjuvant, and metastatic settings. Notably, there has been a groundbreaking development in the treatment of brain metastasis, historically associated with poor prognosis in oncology but showcasing impressive results in melanoma patients. This review article provides a comprehensive synthesis of the most recent knowledge on staging and prognostic factors while highlighting emerging therapeutic modalities, with a particular focus on neoadjuvant and adjuvant strategies, notably immunotherapy and targeted therapies, including the ongoing trials.

Nucleation dynamics of a model biomolecular liquid.

Liquid-liquid phase separation in biology has recently been shown to play a major role in the spatial control of biomolecular components within the cell. However, as they are phase transitions, these processes also display nontrivial dynamics. A model phase-separating system of DNA nanostars provides unique access to nucleation physics in a biomolecular context, as phase separation is driven near room temperature by highly thermo-responsive DNA hybridization and at modest DNA concentrations. By measuring the delay time for phase-separated droplets to appear, we demonstrate that the dynamics of DNA nanostar phase separation reflect that of a metastable binary mixture of patchy particles. For sufficiently deep temperature quenches, droplets undergo spinodal decomposition and grow spontaneously, driven by Brownian motion and coalescence of phase-separated droplets, as confirmed by comparing experimental measurements to particle-based simulations. Near the coexistence boundary, droplet growth slows substantially, indicative of a nucleation process. The temperature dependence of droplet appearance times can be predicted by a classical nucleation picture with mean field exponents and demonstrates that a theory previously used to predict equilibrium phase diagrams can also distinguish spinodal and nucleation dynamical regimes. These dynamical principles are relevant to behaviors associated with liquid-liquid phase separating systems, such as their spatial patterning, reaction coupling, and biological function.

Acute Coxiella burnetii Infection: A 10-Year Clinical Experience at a Tertiary Care Center in the United States.

Background: Identifying and treating patients with acute Q fever who are at an increased risk of progressing to persistent disease is crucial for preventing future complications. In this study, we share our decade-long clinical experience with acute Q fever, highlighting the challenges that clinicians encounter from making an initial diagnosis and performing risk stratification to determining the appropriate prophylaxis regimen and duration. Methods: We retrieved records of adult Mayo Clinic patients (≥18 years) with positive Coxiella burnetii serology results between 1 January 2012 and 31 March 2022. Patients with Q fever anti-phase II immunoglobulin G ≥1:256 by indirect immunofluorescence were further analyzed. Results: Thirty-one patients were included. Their median age was 58 years (IQR, 50-64), and the majority were men (84%). Acute hepatitis (29%), flu-like illness (25.8%), and pneumonia (16%) were the most common presentations. Thirteen patients (42%) received antibiotic prophylaxis to prevent disease progression, with significant variation in the indications and duration across physicians. The combination of doxycycline and hydroxychloroquine was the preferred regimen. Prophylaxis was administered for a median 333 days (IQR, 168-414). Four patients (13%) progressed to Q fever native valve infective endocarditis, with elevated anticardiolipin immunoglobulin G levels being the sole risk factor in 2 cases. The small sample size precluded drawing conclusions on the impact of prophylaxis in preventing disease progression. Conclusions: Management of acute Q fever is complicated by the lack of comprehensive clinical guidelines leading to varied clinical practices. There is a critical need for randomized trials to establish robust evidence-based protocols for management.

Nucleic acid liquids.

The confluence of recent discoveries of the roles of biomolecular liquids in living systems and modern abilities to precisely synthesize and modify nucleic acids (NAs) has led to a surge of interest in liquid phases of NAs. These phases can be formed primarily from NAs, as driven by base-pairing interactions, or from the electrostatic combination (coacervation) of negatively charged NAs and positively charged molecules. Generally, the use of sequence-engineered NAs provides the means to tune microsopic particle properties, and thus imbue specific, customizable behaviors into the resulting liquids. In this way, researchers have used NA liquids to tackle fundamental problems in the physics of finite valence soft materials, and to create liquids with novel structured and/or multi-functional properties. Here, we review this growing field, discussing the theoretical background of NA liquid phase separation, quantitative understanding of liquid material properties, and the broad and growing array of functional demonstrations in these materials. We close with a few comments discussing remaining open questions and challenges in the field.

Sequential Time to Positivity as a Prognostic Indicator in Staphylococcus aureus Bacteremia.

Background: We aimed to determine the factors associated with sequential blood culture time to positivity (STTP) and validate the previously defined time to positivity (TTP) ratio threshold of 1.5 in predicting adverse disease outcomes and mortality of Staphylococcus aureus bacteremia (SAB). Methods: We conducted an observational study of adult patients with SAB. The TTP ratio was calculated by dividing the TTP of the second blood culture by that of the first. Results: Of 186 patients, 69 (37%) were female, with a mean age of 63.6 years. Median TTP was 12 hours (interquartile range [IQR], 10-15 hours) from the initial and 21 hours (17-29) from sequential blood cultures. Methicillin-resistant S aureus (MRSA)-infected patients had significantly shorter STTPs (P < .001) and lower TTP ratios (P < .001) compared to patients with methicillin-susceptible S aureus (MSSA). A significant correlation between initial and STTP was observed in patients with MRSA (r = 0.42, P = .002) but not in those with MSSA. A higher rate of native valve endocarditis (NVE) significantly correlated with a TTP ratio of ≤1.5 (odds ratio, 2.65 [95% confidence interval, 1.3-5.6]; P = .01). The subgroup having an initial TTP <12 hours combined with a TTP ratio ≤1.5 showed the highest prevalence of NVE. Conclusions: The STTP varies based on methicillin susceptibility of S aureus isolate. This study suggests a potential clinical utility of the STTP to identify patients at a higher risk of NVE. However, prospective studies are required to validate these findings.

Characteristics and management of periprosthetic joint infections caused by rapidly growing mycobacteria: a retrospective study and a review of the literature.

Background: Periprosthetic joint infection (PJI) following total joint arthroplasty is a serious complication associated with significant morbidity. While Gram-positive cocci are the predominant causative organisms, PJIs caused by rapidly growing mycobacteria (RGM) have been reported, albeit at a lower frequency. This study aimed to investigate the characteristics and management of PJI caused by RGM. Methods: A retrospective review was conducted using an institutional PJI database to identify patients diagnosed with PJI due to RGM from January 2010 to December 2021. Clinical data, including demographics, symptoms, comorbidity information, laboratory parameters, surgical procedures, medical treatment and outcomes, were collected and analyzed. Results: A total of eight patients were identified with PJI caused by RGM during the study period. The median age was 66 years old, and most cases occurred in patients with total knee arthroplasty (n=6). The isolated RGM species included Mycobacterium abscessus (three cases), M. fortuitum (three cases), and one case each of M. immunogenum and M. mageritense. Surgical debridement was performed in all cases, with six patients undergoing two-stage revision and two patients requiring amputation. Combination antimicrobial therapy was administered based on antimicrobial susceptibility testing, and the median duration of treatment was 7.5 months. Adverse events related to therapy occurred in 75 % of cases. No relapses were observed during the median follow-up period of 39.6 months. Conclusions: PJI caused by RGM is a rare complication of total joint arthroplasty. Surgical debridement and combination antimicrobial therapy are the mainstays of treatment. Although clinical cure rates are high, amputation may be required in severe cases.

Magnetic tweezers characterization of the entropic elasticity of intrinsically disordered proteins and peptoids.

Understanding the conformational behavior of biopolymers is essential to unlocking knowledge of their biophysical mechanisms and functional roles. Single-molecule force spectroscopy can provide a unique perspective on this by exploiting entropic elasticity to uncover key biopolymer structural parameters. A particularly powerful approach involves the use of magnetic tweezers, which can easily generate lower stretching forces (0.1-20 pN). For forces at the low end of this range, the elastic response of biopolymers is sensitive to excluded volume effects, and they can be described by Pincus blob elasticity model that allow robust extraction of the Flory polymer scaling exponent. Here, we detail protocols for the use of magnetic tweezers for force-extension measurements of intrinsically disordered proteins and peptoids. We also discuss procedures for fitting low-force elastic curves to the predictions of polymer physics models to extract key conformational parameters.

Effect of Preoperative Antibiotic Therapy on Operative Culture Yield for Diagnosis of Native Joint Septic Arthritis.

BACKGROUND: Native joint septic arthritis (NJSA) is definitively diagnosed by a positive Gram stain or culture, along with supportive clinical findings. Preoperative antibiotics are known to alter synovial fluid cell count, Gram stain and culture results and are typically postponed until after arthrocentesis to optimize diagnostic accuracy. However, data on the impact of preoperative antibiotics on operative culture yield for NJSA diagnosis are limited. METHODS: We retrospectively reviewed adult cases of NJSA who underwent surgery at Mayo Clinic facilities from 2012-2021 to analyze the effect of preoperative antibiotics on operative culture yield through a paired analysis of preoperative culture (POC) and operative culture (OC) results using logistic regression and generalized estimating equations. RESULTS: Two hundred ninety-nine patients with NJSA affecting 321 joints were included. Among those receiving preoperative antibiotics, yield significantly decreased from 68.0% at POC to 57.1% at OC (p < .001). In contrast, for patients without preoperative antibiotics there was a non-significant increase in yield from 60.9% at POC to 67.4% at OC (p = 0.244). In a logistic regression model for paired data, preoperative antibiotic exposure was more likely to decrease OC yield compared to non-exposure (OR = 2.12; 95% CI = 1.24-3.64; p = .006). Within the preoperative antibiotic group, additional antibiotic doses and earlier antibiotic initiation were associated with lower OC yield. CONCLUSION: In patients with NJSA, preoperative antibiotic exposure resulted in a significant decrease in microbiologic yield of operative cultures as compared to patients in whom antibiotic therapy was held prior to obtaining operative cultures.