High-resolution phenotyping of early acute rejection reveals a conserved alloimmune signature.

Alloimmune responses in acute rejection are complex, involving multiple interacting cell types and pathways. Deep profiling of these cell types has been limited by technology that lacks the capacity to resolve this high dimensionality. Single-cell mass cytometry is used to characterize the alloimmune response in early acute rejection, measuring 37 parameters simultaneously, across multiple time points in two models: a murine cardiac and vascularized composite allotransplant (VCA). Semi-supervised hierarchical clustering is used to group related cell types defined by combinatorial expression of surface and intracellular proteins, along with markers of effector function and activation. This expression profile is mapped to visualize changes in antigen composition across cell types, revealing phenotypic signatures in alloimmune T cells, natural killer (NK) cells, and myeloid subsets that are conserved and that firmly distinguish rejecting from non-rejecting grafts. These data provide a comprehensive, high-dimensional profile of cellular rejection after allograft transplantation.

Establishment of Heterotopic Hind Limb Transplantation Model in the Mouse.

BACKGROUND: The mouse is the most widely used animal for establishing in vivo models in transplant research. However, because of the advanced microsurgical skills required for these operations, the vascularized composite transplantation model in mouse has proven to be technically challenging. The purpose of this report is to describe novel modifications in surgical techniques to establish a consistent and reliable mouse model of hind limb transplantation. METHODS: Forty C57BL/6 male mice, half as donors and half as recipients, were used in this study. The donor hind limb was harvested and transplanted into the recipient's ipsilateral cervical region by anastomosing the donor femoral artery to the recipient common carotid artery with a modified sleeve technique. The donor femoral vein was mounted with a modified cuff and inserted into the recipient external jugular vein. The graft was evaluated at 2 weeks postoperatively. RESULTS: The modified cuff and modified sleeve technique facilitated anastomoses. The time spent on either of the donor operation and recipient operation was about 45 minutes. The graft survival rate was 80% (16 of 20) at 2 weeks after transplant. There was minimal blood loss and no infections were noted. CONCLUSIONS: Revised surgical techniques using a modified cuff proved to be a safe, reliable, and reproducible strategy in establishing a mouse model of hind limb heterotopic transplantation. The consistent graft survival in this syngeneic study demonstrates that this model can serve as a useful tool for further studies in vascularized composite transplantation.

Modifying Crohn's Colitis Recurrence Through Surgery? The Jury Is Still Out.

ABSTRACT: Data suggesting that the mesentery plays an important pathophysiologic role in Crohn's disease and recurrence make the mesentery an attractive therapeutic target during surgical management of Crohn's disease. A new study by Zhu et al. demonstrates that patients with Crohn's colitis who undergo a more extensive mesenteric resection may have a lower rate of needing subsequent operations. We discuss some of the reasons why these data, although much needed by the inflammatory bowel disease community, do not yet sway standard surgical practice for Crohn's colitis.

Fluoroscopic-assisted laparoscopic retrieval of retained glucose sensor wire from the omentum.

We describe a case in which retained wires from a continuous glucose monitor were removed from the abdominal wall and peritoneum of a 6-year-old boy. We highlight a concern for continuous glucose monitor use in children and discuss surgical techniques used to retrieve tiny, mobile objects from complex body cavities.

How Much Time are Physicians and Nurses Spending Together at the Patient Bedside?

BACKGROUND: Bedside rounding involving both nurses and physicians has numerous benefits for patients and staff. However, precise quantitative data on the current extent of physician-nurse (MD-RN) overlap at the patient bedside are lacking. OBJECTIVE: This study aimed to examine the frequency of nurse and physician overlap at the patient beside and what factors affect this frequency. DESIGN: This is a prospective, observational study of time-motion data generated from wearable radio frequency identification (RFID)-based locator technology. SETTING: Single-institution academic hospital. MEASUREMENTS: The length of physician rounds, frequency of rounds that include nurses simultaneously at the bedside, and length of MD-RN overlap were measured and analyzed by ward, day of week, and distance between patient room and nursing station. RESULTS: A total of 739 MD rounding events were captured over 90 consecutive days. Of these events, 267 took place in single-bed patient rooms. The frequency of MD-RN overlap was 30.0%, and there was no statistical difference between the three wards studied. Overall, the average length of all MD rounds was 7.31 ± 0.58 minutes, but rounding involving a bedside nurse lasted longer than rounds with MDs alone (9.56 vs 5.68 minutes, P < .05). There was no difference in either the length of rounds or the frequency of MD-RN overlap between weekdays and weekends. Finally, patient rooms located farther away from the nursing station had a lower likelihood of MD-RN overlap (Pearson's r = -0.67, P < .05). CONCLUSION: RFID-based technology provides precise, automated, and high-throughput time-motion data to capture nurse and physician activity. At our institution, 30.0% of rounds involve a bedside nurse, highlighting a potential barrier to bedside interdisciplinary rounding.

Dual blockade of the PI3K/Akt/mTOR pathway inhibits posttransplant Epstein-Barr virus B cell lymphomas and promotes allograft survival.

Posttransplant lymphoproliferative disorder (PTLD) is a serious complication of organ transplantation that often manifests as Epstein-Barr virus (EBV)-associated B cell lymphomas. Current treatments for PTLD have limited efficacy and can be associated with graft rejection or systemic toxicities. The mTOR inhibitor, rapamycin, suppresses tumor growth of EBV+ B cell lymphoma cells in vitro and in vivo; however, the efficacy is limited and clinical benefits of mTOR inhibitors for PTLD are variable. Here, we show constitutive activation of multiple nodes within the PI3K/Akt/mTOR pathway in EBV+ PTLD-derived cell lines. Inhibition of either PI3K or Akt, with specific inhibitors CAL-101 and MK-2206, respectively, diminished growth of EBV+ B cell lines from PTLD patients in a dose-dependent manner. Importantly, rapamycin combined with CAL-101 or MK-2206 had a synergistic effect in suppressing cell growth as determined by IC50 isobolographic analysis and Loewe indices. Moreover, these combinations were significantly more effective than rapamycin alone in inhibiting tumor xenograft growth in NOD-SCID mice. Finally, both CAL-101 and MK-2206 also prolonged survival of heterotopic cardiac allografts in C57BL/6 mice. Thus, combination therapy with rapamycin and a PI3K inhibitor, or an Akt inhibitor, can be an efficacious treatment for EBV-associated PTLD, while simultaneously promoting allograft survival.

Implementing a Standardized Nurse-driven Rounding Protocol in a Trauma-surgical Intensive Care Unit: A Single Institution Experience.

Introduction Patient care in the trauma-surgical intensive care unit (SICU) requires trust and effective communication between nurses and physicians. Our SICU suffered from poor communication and trust between nurses and physicians, negatively impacting the working environment and, potentially, patient care. Methods A SICU Task Force studied communication practices and identified areas for improvement, leading to several interventions. The daily physician rounding was altered to improve communication and to enhance the role of the registered nurses (RN) in rounds. Additionally, a formal night resident rounding time was implemented. Results A post-intervention survey focusing on cooperation, teamwork, and appreciation between nurses and physicians revealed improvement in these domains. Informal feedback from nurses and physicians indicated improved working relationships and satisfaction with the SICU environment. However, results of a national survey performed after the intervention did not show the same level of improvement. Conclusions A Task Force consisting of SICU nurses and physicians can effectively study a widespread communication issue and implement targeted interventions. While informal feedback may indicate improvement, it can be difficult to demonstrate improvement using formal surveys.

Guilt by association: paradigm for detecting a silent killer (thoracic aortic aneurysm).

Recent studies have confirmed a close association between various medical conditions (intracranial aneurysm, abdominal aortic aneurysm, temporal arteritis, autoimmune disorder, renal cysts), certain aortic anatomic variants (bovine aortic arch, direct origin of left vertebral artery from aortic arch, bicuspid aortic valve), and family history of aneurysm disease with thoracic aortic aneurysm and dissection. This paper reviews these associations. We propose to capitalise on these associations as powerful and expanding opportunities to diagnose the virulent but silent disease of thoracic aortic aneurysm. This can be accomplished by recognition of this 'guilt by association' with the other conditions. Thus, patients with associated diseases and anatomic variants should be investigated for silent aortic aneurysms. Such a paradigm holds substantial potential for reducing death from the silent killer represented by thoracic aortic aneurysm disease.

Natural history of thoracic aortic aneurysms.

Understanding the natural history of thoracic aortic aneurysms (TAAs) is essential to patient care and surgical decision making. In this evidence summary we discuss some of the most clinically relevant features of the disease. The true incidence of TAAs is likely to be higher than currently reported because of the inherently silent nature of TAAs. However, TAAs can become rapidly lethal once dissection or rupture occurs, highlighting the need for more robust screening. The impressive discovery of familial patterns and novel genetic loci for TAAs challenges the idea that most TAAs are simply sporadic. Although the aorta grows in an indolent manner, its rate of growth and its current diameter both have important clinical implications. Biomechanical studies have supported clinical findings of 6.0 cm as a dangerous threshold. Surgical extirpation of TAAs is currently the mainstay of effective treatment. Although endovascular TAA repair is becoming increasingly common, long-term safety remains unproven. We still need more data to support the concept that any medical therapy is effective.

Respecting symptoms in thoracic aortic aneurysm management: a case of symptomatic necrotizing granulomatous aortitis.

A 41-year-old woman presented with chest pain of unclear etiology in the setting of a mildly dilated ascending aorta. Computed tomography angiography showed an aorta with an irregular contour and an aneurysm of 4.5 cm. There was no radiographic evidence of rupture or dissection. The patient was taken to the operating room and was found to have severe aortitis with marked localized wall thinning at imminent risk of aortic rupture. Aortic pathology demonstrated necrotizing granulomas of noninfectious etiology. This case illustrates the importance of respecting symptoms in surgical decision making for thoracic aortic aneurysms that may not meet standard interventional criteria.