Nanoparticle targeting of neutrophil glycolysis prevents lung ischemia-reperfusion injury.

Neutrophils exacerbate pulmonary ischemia-reperfusion injury (IRI) resulting in poor short and long-term outcomes for lung transplant recipients. Glycolysis powers neutrophil activation, but it remains unclear if neutrophil-specific targeting of this pathway will inhibit IRI. Lipid nanoparticles containing the glycolysis flux inhibitor 2-deoxyglucose (2-DG) were conjugated to neutrophil-specific Ly6G antibodies (NP-Ly6G[2-DG]).

Defects in vein valve PROX1/FOXC2 antithrombotic pathway in endothelial cells drive the hypercoagulable state induced by trauma and critical illness.

Objectives: Deep venous thrombosis (DVT) causes significant morbidity and mortality after trauma. Recently, we have shown that blood flow patterns at vein valves induce oscillatory stress genes, which maintain an anticoagulant endothelial phenotype that inhibits spontaneous clotting at vein valves and sinuses, is lost in the presence of DVT in human pathological samples, and is dependent on expression of the transcription factor FOXC2. We describe an assay, modifying our mouse multiple injury system, which shows evidence of clinically relevant microthrombosis and hypercoagulability applicable to the study of spontaneous DVT in trauma without requiring direct vascular injury or ligation.

Defining the Microbiome Components (Bacteria, Viruses, Fungi) and Microbiome Geodiversity.

The recognition that a resident community of microbes contributes substantially to human health and disease is one of the emerging great discoveries in modern medicine. This collection of bacteria, archaea, fungi, viruses, and eukaryotes are referred to as microbiota, which together with the individual tissues they inhabit is defined as our individual microbiome. Recent advances in modern DNA sequencing technologies permit the identification, description, and characterization of these microbial communities as well as their variations within and between individuals and groups.

Dysbiome and Its Role in Surgically Relevant Medical Disease.

Several surgically relevant conditions are directly or indirectly influenced by the human microbiome. Different microbiomes may be found within, or along, specific organs and intra-organ variation is common. Such variations include those found along the course of the gastrointestinal tract as well as those on different regions of the skin.

Dysregulation of the leukocyte signaling landscape during acute COVID-19.

The global COVID-19 pandemic has claimed the lives of more than 750,000 US citizens. Dysregulation of the immune system underlies the pathogenesis of COVID-19, with inflammation mediated tissue injury to the lung in the setting of suppressed systemic immune function. To define the molecular mechanisms of immune dysfunction in COVID-19 we utilized a systems immunology approach centered on the circulating leukocyte phosphoproteome measured by mass cytometry.

IL-7 Immunotherapy in a Nonimmunocompromised Patient With Intractable Fungal Wound Sepsis.

A nonimmunocompromised patient developed life-threatening soft tissue infection with , , and that progressed despite maximum antifungal therapies and aggressive debridement. Interleukin-7 immunotherapy resulted in clinical improvement, fungal clearance, reversal of lymphopenia, and improved T-cell function. Immunoadjuvant therapies to boost host immunity may be efficacious in life-threatening fungal infections.

Extrathoracic multiple trauma dysregulates neutrophil function and exacerbates pneumonia-induced lung injury.

Background: Forty percent of critically ill trauma patients will develop an infectious complication. Pneumonia is the most common cause of death of trauma patients surviving their initial insult. We previously demonstrated that polytrauma (PT), defined as two or more severe injuries in at least two areas of the body, induces emergency hematopoiesis characterized by accelerated myelopoiesis in the bone marrow and increased myeloid cell frequency in the peripheral tissues.

Fatal COVID-19 infection in a patient with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: A case report.

Long-chain fatty-acyl CoA dehydrogenase deficiency (LCHADD) is an inborn error of long chain fatty acid oxidation with various features including hypoketotic hypoglycemia, recurrent rhabdomyolysis, pigmentary retinopathy, peripheral neuropathy, cardiomyopathy, and arrhythmias. Various stresses trigger metabolic decompensation. Coronavirus disease 2019 (COVID-19) is a pandemic caused by the RNA virus SARS-CoV-2 with diverse presentations ranging from respiratory symptoms to myocarditis.

Multi-Disciplinary Trauma Evaluation and Management Simulation (MD-TEAMS) training for emergency medicine and general surgery residents.

Background: Successful trauma resuscitation relies on multi-disciplinary collaboration. In most academic programs, general surgery (GS) and emergency medicine (EM) residents rarely train together before functioning as a team.

Methods: In our Multi-Disciplinary Trauma Evaluation and Management Simulation (MD-TEAMS), EM and GS residents completed manikin-based trauma scenarios and were evaluated on resuscitation and communication skills.

Temporary Abdominal Closure Is Associated with Increased Risk for Fungal Intra-Abdominal Infections in Trauma Patients.

Fungal infections are associated with increased morbidity and death. Few studies have examined risk factors associated with post-operative fungal intra-abdominal infections (FIAIs) in trauma patients after exploratory laparotomy. In this study, we evaluated potential risk factors for acquiring post-operative FIAIs and their impact on clinical outcomes.

Comfort care in trauma patients without severe head injury: In-hospital complications as a trigger for goals of care discussions.

Introduction: Many injured patients or their families make the difficult decision to withdraw life-sustaining therapies (WLST) following severe injury. While this population has been studied in the setting of severe traumatic brain injury (TBI), little is known about patients who undergo WLST without TBI. We sought to describe patients who may benefit from early involvement of end-of-life resources.

Undertriage after severe injury among United States trauma centers and the impact on mortality.

Introduction: Severely injured patients should receive definitive care at high acuity trauma centers. The purposes of this study were to determine the undertriage (UT) rate within a national sample of trauma centers and to identify characteristics of UT patients.

Methods: Severely injured adults ≥16 years were identified from the 2010-2012 NTDB.

Pseudohypoaldosteronism presenting with thrombocytosis and bilateral pneumothoraces in an infant.

Pseudohypoaldosteronism type 1 (PHA-1) is a rare salt-wasting syndrome caused by a peripheral resistance to aldosterone. Here, we describe an unusual presentation of the autosomal dominant PHA-1 featuring bilateral pneumothoraces at birth, thrombocytosis in infancy, and hypercalcemia in addition to the well-described findings of hyponatremia, hyperkalemia, and failure to thrive. These findings contribute to the limited case descriptions of PHA-1 and may suggest additional diagnostic considerations in a neonate presenting with hyperkalemia, hyponatremia, and failure to thrive.

Sonic Hedgehog signaling impairs ionizing radiation-induced checkpoint activation and induces genomic instability.

The Sonic Hedgehog (Shh) pathway plays important roles in embryogenesis, stem cell maintenance, tissue repair, and tumorigenesis. Haploinsufficiency of Patched-1, a gene that encodes a repressor of the Shh pathway, dysregulates the Shh pathway and increases genomic instability and the development of spontaneous and ionizing radiation (IR)-induced tumors by an unknown mechanism. Here we show that Ptc1(+/-) mice have a defect in the IR-induced activation of the ATR-Chk1 checkpoint signaling pathway.

Sirolimus for angiomyolipoma in tuberous sclerosis complex or lymphangioleiomyomatosis.

Background: Angiomyolipomas in patients with the tuberous sclerosis complex or sporadic lymphangioleiomyomatosis are associated with mutations in tuberous sclerosis genes resulting in constitutive activation of the mammalian target of rapamycin (mTOR). The drug sirolimus suppresses mTOR signaling.

Methods: We conducted a 24-month, nonrandomized, open-label trial to determine whether sirolimus reduces the angiomyolipoma volume in patients with the tuberous sclerosis complex or sporadic lymphangioleiomyomatosis.

Levetiracetam as adjunctive antiepileptic therapy for patients with tuberous sclerosis complex: a retrospective open-label trial.

Seizures are a common neurologic symptom of tuberous sclerosis complex. The use of levetiracetam as adjunctive antiepileptic therapy was assessed in 20 patients with tuberous sclerosis complex aged 2 to 19 years. In this retrospective evaluation, 40% of patients treated with levetiracetam achieved a seizure reduction of more than 50%.