Isolated spontaneous dissection of the superior mesenteric artery (SMA) and celiac artery (CA) remains a rare condition; however, it has been increasingly noted incidentally on diagnostic imaging. ...The purpose of this study was to examine the natural history and outcomes of patients presenting with isolated spontaneous mesenteric artery dissection (SMAD). We hypothesized that most SMADs can be treated nonoperatively.
This was a single-center retrospective review of patients presenting with the diagnosis of SMAD between 2006 and 2016. Data analysis included demographics, clinical data, radiologic review, treatment, and outcomes.
A total of 77 patients were found to have CA dissection, SMA dissection, or both in the absence of aortic dissection diagnosed on computed tomography or magnetic resonance imaging. The average age was 56 years (range, 26-86 years), 80% were male, and 10 patients (13%) had underlying connective tissue disorders. The majority, 64%, presented with symptoms including abdominal pain, back pain, and chest pain; the remaining 36% were asymptomatic. Combined SMA and CA dissection was found in 14 (18%) patients; 33 (43%) presented with isolated CA dissection, and 30 (39%) presented with isolated SMA dissection. Only four patients required intervention. Mesenteric bypass was performed in two patients, and SMA endarterectomy with patch angioplasty was performed in one patient for signs of bowel ischemia. No patient required bowel resection. The two bypasses were anastomosed to a branch of the SMA, and complete lumen restoration was seen on long-term imaging follow-up. One patient underwent stent grafting of the CA and hepatic artery for aneurysmal degeneration 1 month after diagnosis. The remaining 73 patients were managed nonoperatively; 40 (52%) were treated with a short course of anticoagulation, 23 (30%) were treated with antiplatelet therapy, and 10 (13%) were treated with observation alone. No other late interventions or recurrences were noted during a mean follow-up of 21 months.
Whereas isolated SMAD poses a risk of visceral ischemia, most patients presenting with this diagnosis can be treated nonoperatively with a short course of antiplatelet or anticoagulant therapy. Only a small number of patients require surgical revascularization for bowel ischemia.
Noncompressible torso hemorrhage is a leading cause of mortality in civilian and battlefield trauma. We sought to develop an i.v.-injectable, tissue factor (TF)-targeted nanotherapy to stop ...hemorrhage. Tissue factor was chosen as a target because it is only exposed to the intravascular space upon vessel disruption. Peptide amphiphile (PA) monomers that self-assemble into nanofibers were chosen as the delivery vehicle. Three TF-binding sequences were identified (EGR, RLM, and RTL), covalently incorporated into the PA backbone, and shown to self-assemble into nanofibers by cryo-transmission electron microscopy. Both the RLM and RTL peptides bound recombinant TF in vitro. All three TF-targeted nanofibers bound to the site of punch biopsy-induced liver hemorrhage in vivo, but only RTL nanofibers reduced blood loss versus sham (53% reduction, p < 0.05). Increasing the targeting ligand density of RTL nanofibers yielded qualitatively better binding to the site of injury and greater reductions in blood loss in vivo (p < 0.05). In fact, 100% RTL nanofiber reduced overall blood loss by 60% versus sham (p < 0.05). Evaluation of the biocompatibility of the RTL nanofiber revealed that it did not induce RBC hemolysis, did not induce neutrophil or macrophage inflammation at the site of liver injury, and 70% remained intact in plasma after 30 min. In summary, these studies demonstrate successful binding of peptides to TF in vitro and successful homing of a TF-targeted PA nanofiber to the site of hemorrhage with an associated decrease in blood loss in vivo. Thus, this therapeutic may potentially treat noncompressible hemorrhage.
Targeting of vascular intervention by systemically delivered supramolecular nanofibers after balloon angioplasty is described. Tracking of self‐assembling peptide amphiphiles using fluorescence shows ...selective binding to the site of vascular intervention. Cylindrical nanostructures are observed to target the site of arterial injury, while spherical nanostructures with an equivalent diameter display no binding.
Cardiovascular interventions continue to fail as a result of arterial restenosis secondary to neointimal hyperplasia. We sought to develop and evaluate a systemically delivered nanostructure targeted ...to the site of arterial injury to prevent neointimal hyperplasia. Nanostructures were based on self-assembling biodegradable molecules known as peptide amphiphiles. The targeting motif was a collagen-binding peptide, and the therapeutic moiety was added by S-nitrosylation of cysteine residues.
Structure of the nanofibers was characterized by transmission electron microscopy and small-angle X-ray scattering. S-nitrosylation was confirmed by mass spectrometry, and nitric oxide (NO) release was assessed electrochemically and by chemiluminescent detection. The balloon carotid artery injury model was performed on 10-week-old male Sprague-Dawley rats. Immediately after injury, nanofibers were administered systemically via tail vein injection. S-nitrosylated (S-nitrosyl SNO)-targeted nanofibers significantly reduced neointimal hyperplasia 2 weeks and 7 months following balloon angioplasty, with no change in inflammation.
This is the first time that an S-nitrosothiol (RSNO)-based therapeutic was shown to have targeted local effects after systemic administration. This approach, combining supramolecular nanostructures with a therapeutic NO-based payload and a targeting moiety, overcomes the limitations of delivering NO to a site of interest, avoiding undesirable systemic side effects.
We successfully synthesized and characterized an RSNO-based therapy that when administered systemically, targets directly to the site of vascular injury. By integrating therapeutic and targeting chemistries, these targeted SNO nanofibers provided durable inhibition of neointimal hyperplasia in vivo and show great potential as a platform to treat cardiovascular diseases.
To describe the components of targeted nanotherapeutics and to review their applications in the treatment of surgical diseases.
Targeted nanotherapeutic is a novel strategy for treating a variety of ...diseases and is an emerging technology that offers advantages over current treatment strategies. The nanoscale size, combined with the ability to surface functionalize the delivery vehicle to enable targeting and incorporate a therapeutic payload, provides a new and innovative therapeutic platform to treat surgical diseases that has yet to be fully realized in the surgical arena.
A comprehensive literature review of nanotherapeutics, targeting strategies, and their utility in treating surgical diseases is performed.
Targeted nanotherapeutics have demonstrated safety and biocompatibility in treating surgical diseases. The ability to surface functionalize the nanoparticles affords a unique tailorability that enables targeting specificity and therapeutic payload delivery to treat a variety of surgical diseases. Moreover, the small size and targeting capabilities allow access to biological compartments, such as the blood-brain barrier, that have previously been difficult to treat.
Targeted nanotherapeutics represent a novel therapeutic platform and have great potential to impact the treatment of surgical diseases.
Hemorrhage is the leading cause of death in military trauma and second leading cause of death in civilian trauma. Although many well-established animal models of hemorrhage exist in the trauma and ...anticoagulant literature, few focus on directly quantitating blood loss.
To establish and validate a reproducible rodent model of uncontrolled hemorrhage to serve as the foundation for developing therapies for noncompressible torso trauma.
We developed and evaluated 4 different hemorrhage models using male Sprague-Dawley rats (6 rats/model), aged 10 to 14 weeks and weighing 330 to 460 g, at the Department of Surgery, Northwestern University.
We used tail-cut (4 cm), liver punch biopsy (12 mm), liver laceration (3.0 × 1.5 cm), and spleen transection models. All animals underwent invasive hemodynamic monitoring.
Blood loss, expressed as a percentage of total blood volume (TBV), mean arterial pressure, and heart rate, which were recorded at 2- to 5-minute intervals.
The tail-cut model resulted in a mean (SD) TBV loss of 15.4% (6.0%) with hemodynamics consistent with class I hemorrhagic shock. The liver punch biopsy model resulted in a mean (SD) TBV loss of 16.7% (3.3%) with hemodynamics consistent with class I hemorrhagic shock. The liver laceration model resulted in a mean (SD) TBV loss of 19.8% (3.0%) with hemodynamics consistent with class II hemorrhagic shock. The spleen transection model resulted in the greatest blood loss (P < .01), with a mean (SD) TBV loss of 27.9% (3.4%) and hemodynamics consistent with class II hemorrhagic shock. The liver laceration and punch biopsy models resulted in most of the blood loss within the first 2 minutes, whereas the spleen transection and tail-cut models resulted in a steady loss during 10 minutes. The liver laceration and spleen transection models resulted in the greatest degree of hemodynamic instability (mean SD arterial pressure decreases of 25 1 and 41 11 mm Hg, respectively). One-hour survival was 100% in all 4 models.
We established and validated the reproducibility of 4 different rat models of uncontrolled hemorrhage. These models provide a foundation to design novel nonsurgical therapies to control hemorrhage, and the different degrees of hemorrhagic shock produced from these models allow for flexibility in experimental design.
The nineteen stories in The Seven Autopsies of Nora Hanneman track the splintered trajectory of the title character, tracing a chicken-scratch line of psychosexual development from childhood to old ...age.?
In unfamiliar and sometimes bizarre narrative turns, the stories in Courtney E. Morgan’s The Seven Autopsies of Nora Hanneman traverse the gamut of female/human experience, both grounded in reality and in the irreal. Two schoolgirls culminate their sexual exploration in a surreal act of cannibalism. A sister molds her dead brother’s body into a bird. A woman gives birth to balls of twine and fur (among other things). A sex worker engages a version of herself in a brothel of prostituted body parts.
Morgan tears apart a host of archetypes and tropes of femininity—dismembering them, skinning them, and then draping them one by one over her characters like fur coats—revealing them as ill-fitting, sometimes comedic, sometimes monstrous, and always insufficient, masks. Along with these skins of the cultural “feminine,” the collection tries on an array of genres—dissecting, mutating, and breeding them together—from fairy tale to horror, surrealism to confessional (non)fiction, and erotica to (un)creation myth.
The book weaves around questions of sexuality, identity, and subjectivity. Mutability, instability, and liminality are foregrounded, both in content and form, character and language—blurring the lines between birth and death, death and sex, tugging at the transitional spaces of adolescence and gestation. Even as its treatment is essentialized, gender is muddied and obscured. Morgan shows off her linguistic range in this collection, from sharp-as-nails prose to lyrical moments of poetic reach—probing the extremes of the human condition through both narrative line and language itself.
Meniscus allograft transplantation (MAT) has been shown to be a feasible surgical option for younger patients, below 50 years of age who have meniscal insufficiency and have failed conservative ...treatment measures. In this technical note, we describe a procedure of harvesting and injecting bone marrow aspirate concentrate in a meniscus allograft during a MAT procedure, which may allow for longer lasting transplants and improve patient outcomes. In this technical note, bone marrow aspirate concentrate is harvested arthroscopically from the intercondylar notch at the surgical site, which prevents additional donor site morbidity, as seen with harvesting from other locations, such as the iliac crest. This also reduces operating time, since harvesting from the iliac crest requires different patient positioning and usually additional anesthesia. The authors of this surgical technique believe that biological augmentation during MATs will assist surgeons in maximizing graft survivorship and, ultimately, lead to better patient outcomes.
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Background:
Lower extremity amputations from diabetic foot ulcers (DFUs) are rebounding, and new biomarkers that predict wound healing are urgently needed. Anaerobic bacteria have been associated ...with persistent ulcers and may be a promising biomarker beyond currently recommended vascular assessments. It is unknown whether anaerobic markers are simply a downstream outcome of peripheral arterial disease (PAD) and ischemia, however. Here, we evaluate associations between two measures of anaerobic bacteria—abundance and metabolic activity—and PAD.
Methods:
We built a prospective cohort of 37 patients with baseline ankle brachial index (ABI) results. Anaerobic bacteria were measured in two ways: DNA-based total anaerobic abundance using 16S rRNA gene amplicon sequencing and resulting summed relative abundance, and RNA-based metabolic activity based on bacterial read annotation of metatranscriptomic sequencing. PAD was defined three ways: PAD diagnosis, ABI results, and a dichotomous definition of mild ischemia (versus normal) based on ABI values. Statistical associations between anaerobes and PAD were evaluated using univariate odds ratios (ORs) or Spearman’s correlations.
Results:
Total anaerobe abundance was not significantly associated with PAD diagnosis, ABI results, or mild ischemia (ORPAD = 0.47, 95% CI = 0.023–7.23, p = 0.60; Spearman’s correlation coefficientABI = 0.24, p = 0.17; ORmild ischemia = 0.25, 95% CI = 0.005–5.86, p = 0.42). Anaerobic metabolic activity was not significantly associated with PAD diagnosis, ABI results, or mild ischemia (ORPAD = 1.99, 95% CI = 0.17–21.44, p = 0.57; Spearman’s correlation coefficientABI = 0.12, p = 0.52; ORmild ischemia = 0.90, 95% CI = 0.03–15.16, p = 0.94).
Conclusion:
Neither anaerobic abundance nor metabolic activity was strongly associated with our three definitions of PAD. Therefore, anaerobic bacteria may offer additional prognostic value when assessing wound healing potential and should be investigated as potential molecular biomarkers for DFU outcomes.
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