Citations

If the septal component of a nasal injury is adequately managed, usually the entire nasal injury will be well managed. Major or minor nasal trauma can cause cartilage fracture, deviation, dislocation, hematoma, or abscess formation, and the various associated sequelae, some of them life-threatening. A negative x-ray report should never be used as a substitute for a complete intranasal examination in any child with nasal trauma. Any nasal abnormality should be referred for immediate evaluation and treatment.

Approximately 80% of pancreatic cancer patients suffer from cachexia, and one-third die due to cachexia-related complications such as respiratory failure and cardiac arrest. Although there has been considerable research into cachexia mechanisms and interventions, there are, to date, no FDA-approved therapies. A major contributing factor for the lack of therapy options could be the failure of animal models to accurately recapitulate the human condition. In this study, we generated an aged model of pancreatic cancer cachexia to compare cachexia progression in young versus aged tumor-bearing mice. Comparative skeletal muscle transcriptome analyses identified 3-methyladenine (3-MA) as a candidate antiwasting compound. In vitro analyses confirmed antiwasting capacity, while in vivo analysis revealed potent antitumor effects. Transcriptome analyses of 3-MA–treated tumor cells implicated Perp as a 3-MA target gene. We subsequently (a) observed significantly higher expression of Perp in cancer cell lines compared with control cells, (b) noted a survival disadvantage associated with elevated Perp , and (c) found that 3-MA–associated Perp reduction inhibited tumor cell growth. Finally, we have provided in vivo evidence that survival benefits conferred by 3-MA administration are independent of its effect on tumor progression. Taken together, we report a mechanism linking 3-MA to Perp inhibition, and we further implicate Perp as a tumor-promoting factor in pancreatic cancer.

Abstract Background Nontuberculous mycobacteria (NTM) are resistant to numerous antibiotics and lead to significant morbidity and mortality. Omadacycline (OMC) is an aminomethylcycline antibiotic that is Food and Drug Administration-approved for acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia. Furthermore, OMC has shown in vitro activity against NTM. Given that real-world evidence is lacking, our primary objective was to evaluate the clinical success and tolerability of OMC when used for a variety of NTM infections. Methods This was a multicenter, retrospective, observational study conducted from January 2020 to June 2021. We included all patients ≥ 18 years of age that received OMC of any indication for Mycobacterium spp. The primary outcome was clinical success, defined as a lack of all-cause mortality, lack of persistence or re-emergence of infection during or after therapy, and lack of alteration of OMC. Incidence of adverse effects potentially attributable to OMC and reasons for OMC utilization were also analyzed. Results A total of 31 patients were included from 12 geographically distinct academic health systems (median age: 57 (IQR, 45-63) years; 45% male; 81% Caucasian). The majority of isolated pathogens were Mycobacterium abscessus complex (84%) and of those with subspeciation performed (54%), the majority (86%) were subsp. abscessus. The primary infections were of pulmonary origin (67%) and the median (IQR) duration of OMC therapy was 5.3 (3.2-9.4) months. Most isolates did not have OMC susceptibility conducted (87%), while the majority did for tigecycline (90%). Clinical success was reported in 81% of the population. Most patients were on combination antimicrobial therapy, and 39% of patients reported an adverse effect while on OMC (58% gastrointestinal distress). The majority of patients were prescribed OMC due to ease of administration (61%) and antimicrobial resistance to previous antibiotics (42%). Conclusion OMC may be a potential option for the therapy of NTM infections. Prospective, randomized clinical trials are needed to confirm our preliminary findings. Disclosures Julie V. Philley, MD, Paratek Pharmaceuticals (Advisor or Review Panel member)Paratek Pharmaceuticals, Inc. (Consultant) Michael P. Veve, Pharm.D., Cumberland (Grant/Research Support)Paratek Pharmaceuticals (Research Grant or Support) Michael J. Rybak, PharmD, MPH, PhD, Paratek Pharmaceuticals (Research Grant or Support)

Introduction: A common risk factor of chronic, nontraumatic subdural hematoma (SDH) is anticoagulation therapy. Anticoagulation is generally held in patients who develop SDH, but this can lead to thromboembolic events. While prior studies have reported the clinical outcomes of patients with anticoagulation-related SDH, there remains little evidence regarding ongoing anticoagulation treatment. Case Report: We report the management of 2 patients who developed anticoagulation-related SDH and underwent middle meningeal artery (MMA) embolization and successful reinitiation of anticoagulation therapy. In both patients, we conservatively managed anticoagulation with heparin and/or enoxaparin as a bridge to warfarin after MMA embolization. Follow-up computed tomography head revealed interval decrease of SDH and stable neurological status. Conclusions: These cases provide anecdotal evidence of a challenging clinical scenario where there is a necessary indication for therapeutic anticoagulation (ie, venous sinus thrombosis or atrial appendage thrombus) and comorbid SDH. Endovascular MMA embolization may be an effective adjunct therapy for clinical scenarios in patients with SDH and an urgent indication for anticoagulation. Longer follow-up, prospective series, and future randomized clinical trials are needed to objectively assess outcomes in this clinically challenging patient population.

Abstract The management of chronic lymphocytic leukemia (CLL) has undergone unprecedented changes over the last decade. Modern targeted therapies are incorporated into clinical practice. Unfortunately, patients have begun to develop resistance or intolerance to multiple classes. Symptomatic patients previously treated with a BTK inhibitor (BTKi) and venetoclax represent a new and rapidly growing unmet need in CLL. Here, we define unmet needs in a modern treatment context. We also critically review the literature for PI3K inhibitors and chemoimmunotherapy and lack of data to support their utility following BTKis and venetoclax. Finally, we suggest opportunities to ensure the continued innovation for patients with CLL.

Summary: Surgical disease is now among the most common, preventable, and growing contributors to the global burden of disease. The attitudes of trainees toward global surgery and the viability of a global surgery as an academic track have blossomed. More optimized experiences within residency education are necessary, however, to prepare the next generation of global surgeons. The field of plastic surgery is thus at an important crossroads in the effort to incorporate global surgery into training programs in a uniform fashion across the country. The recent American Council of Academic Plastic Surgeons meeting in February 2020 was dedicated to identifying strategies that will enhance the adoption of global surgery practices within plastic surgery. In this article, we discuss the principles, themes, and ideas that emerged from this session, and further develop concrete initiatives believed to be potentially fruitful. Some have been discussed in other surgical disciplines or presented in isolation to the plastic surgery community, but never as a cohesive set of recommendations that take into account the background and shortfalls of the current model for global health education in the 21st century. We then introduce five recommendations to optimize learner education: (1) clarification of learner expectations and roles; (2) domestic teaching for optimization of field experiences; (3) expansion of longitudinal, formal rotations; (4) strengthening of the role of research; and (5) integration of program financing.