Dalbavancin as an alternative to traditional outpatient parenteral antimicrobial therapy for deep gram-positive infections - an observational, retrospective review.

Background: Treatment of invasive gram-positive infections in complex patient populations is challenging. Dalbavancin, approved for skin and soft tissue infections, offers advantages in this setting due to its long half-life and infrequent dosing. However, less is known about the outcomes of off-label dalbavancin for deeper infections. Objectives: The objective of this study is to examine the feasibility and outcomes of patients with complex gram-positive infections treated with dalbavancin as an alternative to standard outpatient parenteral antimicrobial therapy (OPAT). Methods: We conducted a multicenter, retrospective review of adult patients managed within an OPAT program with intravenous dalbavancin for off-label indications. Adult patients were included if they had treatment details and follow-up documented between January 2020 and June 2023. Details of dalbavancin use including indications for prescription were captured. Outcomes of interest included 90-day infection recurrence, prosthesis retention rates, 90-day mortality, and adverse medication events. Results: In all, 61 patients received dalbavancin, mostly as sequential therapy. Twenty-three percent received dalbavancin strictly in the outpatient setting. Dalbavancin was used primarily for hardware (fracture, spine, or joint), native bone or joint, and complicated soft tissue infections. The predominant pathogen was Staphylococcus aureus (61%). Dalbavancin was frequently prescribed as a two-dose 1500 mg regimen (49%) due to persistent infection (23%), difficult line access (30%), difficulty achieving therapeutic vancomycin levels (18%), or substance abuse history (18%). Overall, six patients (10%) had infection recurrence and no patients died during the follow-up period. Three of eight patients with hardware retention had infection recurrence. Adverse effects were minimal and mostly self-limiting. Conclusion: Dalbavancin is an efficacious and safe alternative to standard OPAT, especially in those with barriers to traditional long-term intravenous antibiotics. Improved outcomes may be achieved with hardware removal. Dalbavancin may facilitate early discharge or prevent hospitalizations. Comparative studies of standard OPAT regimens versus dalbavancin are needed.

Injuries Common to the Brazilian Jiu-Jitsu Practitioner.

BACKGROUND: Brazilian jiu-jitsu (BJJ) is a martial art that focuses on ground combat, emphasizing skill over strength and submission over striking. The purpose of this study is to evaluate the nature of injuries affecting practitioners of BJJ in the settings of competition, training, and conditioning. METHODS: An online survey was created to collect demographic and injury-specific information. This survey was distributed to the 234 schools in the United States registered with the International Brazilian Jiu-Jitsu Federation (IBJJF). The survey was also distributed to local BJJ schools and at local tournaments in the Greater New York City area. Data from a total of N=56 participants were recorded for this survey. RESULTS: The majority of participants were male (n=44, 78.6%) and amateur competitors (n=29, 51.8%) with an average duration of BJJ training of 6.9 ± 5.9 years. The majority of participants (82.1%) train at least six hours per week and compete in an average of 4.6 ± 2.5 competitions per year. The most common injuries were to the finger/hand (78.6%) and knee (61.5%). The most commonly reported fracture was of the hand/fingers (n=6). Of the 156 total injuries reported, 133 (85.3%) occurred during practice or training rather than in competition and 76 (48.7%) required medical attention. Few injuries required surgical intervention. CONCLUSIONS: This study provides novel information regarding injury characteristics of BJJ practitioners with respect to the level of training and use of protective equipment that can guide expectations and management for this unique group of athletes. Amateur BJJ practitioners are the most commonly injured, and largely experience injuries of the upper extremities during training or conditioning rather than during competition.

Treatment of an Infected Tibial Shaft Non-Union Using a Novel 3D-Printed Titanium Mesh Cage: A Case Report.

Treating large bone defects resulting from trauma, tumors, or infection can be challenging, as current methods such as external fixation with bone transport, bone grafting, or amputation often come with high costs, high failure rates, high requirements for follow-up, and potential complications. In this case report, we present the successful treatment of a complicated, infected tibial shaft non-union by using a personalized three-dimensional (3D)-printed titanium mesh cage. This case adds to the existing body of literature by demonstrating successful integration of bone into a titanium implant and a demonstration of immediate postoperative weight bearing in the setting of suboptimal operative and psychosocial conditions. Futhermore, this report highlights the flexibility of 3D-printing technology and its ability to allow for continued limb salvage, even after a planned bone transport procedure has been interrupted. The use of 3D-printed implants customized to the patient's specific needs offers a promising new avenue for treating complex tibial pathologies, and the technology's versatility and ability to be tailored to individual patients makes it a promising tool for addressing a wide range of bone defects.

Increased morbidity and mortality in elderly patients with lower extremity trauma and associated injuries: A review of 420,066 patients from the national trauma database.

INTRODUCTION: There is a paucity of research addressing the morbidity and mortality associated with polytrauma in elderly patients. This study aimed to compare the outcomes of elderly trauma patients with an isolated lower extremity fracture, to patients lower extremity fractures and associated musculoskeletal injuries. METHODS: This study is a retrospective review from the National Trauma Database (NTDB) between 2008 and 2014. ICD 9 codes were used to identify patients 65 years and older with lower extremity fractures. Patients were categorize patients into three sub groups: patients with isolated lower extremity fractures (ILE), patients with two or more (multiple) lower extremity fractures (MLE) and, patients with at least one upper and at least one lower extremity fracture (ULE). Groups were stratified into patients age 65-80 and patients >80 years of age. RESULTS: A total 420,066 patients were included in analysis with 356,120 ILE fracture patients, 27,958 MLE fracture patients, and 35,988 ULE fracture patients. The MLE group reported the highest dispatch to ACS level 1 trauma centers at 31.8% followed by the ULE group at 28.5% and the ILE group at 24.7% of patients (p<0.001). The overall rate of complications was highest in the MLE group followed by the ULE and then the ILE group (41.4%, 40.3%, 36.1%, respectively p<0.001). Motility rates in patients >80 years old in the MLE group and ULE group were similar (1.483 vs 1.4432). However, in the 65-80 year group the odds of mortality was 1.260 in the MLE group and 1.450 in the ULE group (p<0.001), such that the odds of mortality after sustaining a MLE fracture increases with age, whereas this effect was not seen in the ULE group. CONCLUSION: Patients who sustained MLE and ULE fractures, had increased mortality, complications and in hospital care requirements as compared to patients with isolated lower extremity injuries. These outcomes are comparable between ULE and MLE fracture patients over the age of 80 however patients 65-80 with ULE fractures had increased mortality as compared patients 65-80 with MLE fractures. Understanding the unique considerations and requirements of elderly trauma patients is vital to providing successful outcomes.

Beta-hemolytic group a streptococcal orthopaedic infections: Our institutional experience and review of the literature.

Group A streptococcal (GAS) infections have high morbidity and mortality due to toxin production and tissue invasion. We reviewed all orthopaedic GAS infections at our medical centre between January 2017 and April 2019. Median age was 56 years. At least 60% had a body mass index (BMI) of ≥30 kg/m2. Median Charlson comorbidity score was 3 (range 0-7). Clinical cure at 90 days was achieved in only 62%. All 4 patients with underlying orthopaedic hardware were cured. Toxin-neutralizing antibiotics and intravenous immunoglobulin were underutilized. Our review confirms poor outcomes from GAS orthopaedic infections without optimal management.

A Comprehensive Review of Analgesia and Pain Modalities in Hip Fracture Pathogenesis.

PURPOSE OF REVIEW: Hip fracture is common in the elderly population, painful and costly. The present investigation was undertaken to review epidemiology, socio-economic and medical implications, relevant anatomy, and anesthetic and pain modalities of hip fracture. RECENT FINDINGS: A literature search of PubMed, Ovid Medline, and Cochrane databases was conducted in December 2018 to identify relevant published clinical trials, review articles, and meta-analyses studies related to anesthetic and pain modalities of hip fracture. The acute pain management in these situations is often challenging. Common issues associated with morbidity and mortality include patients' physiological decrease in function, medical comorbidities, and cognitive impairment, which all can confound and complicate pain assessment and treatment. Perioperative multidisciplinary and multimodal approaches require medical, surgical, and anesthesiology teams employing adequate preoperative optimization. Reduction in pain and disability utilizing opioid and non-opioid therapies, regional anesthesia, patient-tailored anesthetic approach, and delirium prevention strategies seems to ensure best outcomes.

Treatment of a complex orthopaedic infection due to extensively drug-resistant Pseudomonas aeruginosa.

According to the Centers for Disease Control and Prevention (CDC), approximately 51 000 healthcare-associated infections caused by Pseudomonas aeruginosa occur annually in the USA, more than 6000 of which (13%) are caused by multidrug resistant (MDR) strains. Ceftolozane/tazobactam (TOL/TAZ) (Zerbaxa) was approved by the US Food and Drug Administration (FDA) in December 2014 for the treatment of complicated intra-abdominal and urinary tract infections. At this time, clinical data on the role of TOL/TAZ treatment outside of FDA-approved indications is limited. Herein, we present a case of extensively drug-resistant (XDR) P. aeruginosa osteomyelitis of the upper extremity, which was successfully treated with TOL/TAZ for 8 weeks with optimal clinical and laboratory responses. Monotherapy with TOL/TAZ appears effective for treatment of complicated bone and joint infections with XDR P. aeruginosa in combination with comprehensive surgical management, particularly when few antibiotic options exist.

Targeted therapy of osteosarcoma with radiolabeled monoclonal antibody to an insulin-like growth factor-2 receptor (IGF2R).

INTRODUCTION: Osteosarcoma overall survival has plateaued around 70%, without meaningful improvements in over 30years. Outcomes for patients with overt metastatic disease at presentation or who relapse are dismal. In this study we investigated a novel osteosarcoma therapy utilizing radioimmunotherapy (RIT) targeted to IGF2R, which is widely expressed in OS. METHODS: Binding efficiency of the Rhenium-188(188Re)-labeled IGF2R-specific monoclonal antibody (mAb) to IGF2R on OS17 OS cells was assessed with Scatchard plot analysis. Biodistribution studies were performed in heterotopic murine osteosarcoma xenografts. Tumor growth was compared over a 24-day period post-treatment between mice randomized to receive 188Re-labeled IGF2R-specific murine mAb MEM-238 (188Re-MEM-238) or one of three controls: 188Re-labeled isotype control mAb, unlabeled MEM-238, or no treatment. RESULTS: Results demonstrate that the radioimmunoconjugate had a high binding constant to IGF2R. Both 188Re-MEM-238 and the isotype control had similar initial distribution in normal tissue. After 48h 188Re-MEM-238 exhibited a 1.8 fold selective uptake within tumor compared to the isotype control (p=0.057). Over 24days, the tumor growth ratio was suppressed in animals treated with RIT compared to unlabeled and untreated controls (p=0.005) as demonstrated by a 38% reduction of IGF2R expressing osteosarcoma cells in the RIT group (p=0.002). CONCLUSIONS: In conclusion, given the lack of new effective therapies in osteosarcoma, additional investigation into this target is warranted. ADVANCES IN KNOWLEDGE: High expression of IGF2R on osteosarcoma tumors, paired with the specificity and in vivo anti-cancer activity of 188Re-labeled IGF2R-specific mAb suggests that IGF2R may represent a novel therapeutic target in the treatment of osteosarcoma. IMPLICATIONS FOR PATIENT CARE: This targeted approach offers the benefits of being independent of a specific pathway, a resistance mechanism, and/or an inherent biologic tumor trait and therefore is relevant to all OS tumors that express IGF2R.

Reducing Postoperative Fracture Displacement After Locked Plating of Proximal Humerus Fractures: Current Concepts.

The incidence of proximal humerus fractures in the elderly has been rising. Concomitantly, operative fixation with use of locking plates has been increasing. Postoperative complications of locking plate fixation, particularly in the setting of osteoporotic bone, include screw penetration of the articular surface, progressive fracture displacement, and avascular necrosis. Intraoperative techniques to enhance the fixation construct and reduce complications include use of rotator cuff sutures, bone void fillers (fibular strut allograft, cancellous allograft, autograft, bone cement), appropriate placement of divergent and shorter locking screws, and medial calcar reduction and support. More recent clinical and biomechanical studies suggest that use of these strategies may reduce complications after locked plating of osteoporotic proximal humerus fractures. Furthermore, a multidisciplinary approach to the evaluation and treatment of osteoporosis may be beneficial in these patients.

Molybdenum scavenging by iron monosulfide.

Molybdenum profiles in dated sediment cores provide useful historical information about anoxia in anthropogenically impacted natural waters but would be of greater service if Mo fixation mechanisms were better understood. Here, we explore Mo scavenging by precipitated FeS in a model system consisting of an FeIII-bearing kaolinite (KGa-1B) dispersed in NaHS solutions. Test solutions contain 18 microM thiomolybdates (mainly MoOS3(2-)). Optically measuring dissolved polysulfides monitors the rate of FeS production from FeIII minerals. Even though the exposed clay surface area is large (450 m2/L), the clay itself sorbs little Mo at pH 8.6. As FeS forms, Mo is taken up in initial Mo/Fe mole ratios of 0.04-0.06, irrespective of HS- concentration (4-40 mM range). After about a day, Mo expulsion from the solids begins, accompanied by net polysulfide consumption. These changes reflect recrystallization of amorphous FeS to more ordered products such as greigite. FeS captures some MoO4(2-) but captures thiomolybdates more effectively. Kaolinite accelerates conversion of MoOS3(2-) to MoS4(2-), as predicted previously, and thiomolybdates facilitate reduction of FeIII minerals in the clay compared to Mo-free solutions. FeS is a potentially effective, transient scavenging agent for Mo in sulfidic environments, although FeS2 and organic matter appear to be the ultimate sedimentary hosts.