Application and outcomes of extracorporeal life support in emergency general surgery and trauma.

BACKGROUND: We analyzed the use of Extracorporeal Membranous Oxygenation (ECMO) in acute care surgery patients at our Level-1 trauma center. We hypothesized that this patient population has improved ECMO outcomes. METHODS: This was a retrospective analysis of emergency general surgery and trauma patients placed on ECMO between the periods of October 2013 and February 2020. There were 10 surgical and 12 trauma patients studied, who eventually required ECMO support. ECMO support and ECMO type/modality were analyzed with injury and survival prognostic scores examined. MAIN RESULTS: Overall, 16 of the 22 patients survived to hospital discharge, for a survival rate of 73%. Mean age was 34.18 years. Mean hospital length of stay was 23.4 days with mean days on ECMO equal to 7.5. The net negative fluid balance was 5.36 L. CONCLUSIONS: The survival of our ECMO cohort is notably higher than previously cited studies. Our group demonstrated decreased length of time on ECMO, decreased length of stay in the hospital, and similar rates of complications compared to prior reports. ECMO is a useful modality in acute care surgical patients and should be considered in these patient populations. Our focus on net negative fluid balance for ECMO patients demonstrates improved survival. ECMO should be considered early in surgical patients and early in advanced trauma life support.

ECMO after cardiac surgery: a single center study on survival and optimizing outcomes.

BACKGROUND: The study purpose is to examine survival prognostic and extracorporeal membrane oxygenation (ECMO) application outcomes at our tertiary care center. METHODS: This is a retrospective analysis, January 2014 to September 2019. We analyzed 60 patients who underwent cardiac surgery and required peri-operative ECMO. All inpatients with demographic and intervention data was examined. 52 patients (86.6%) had refractory cardiogenic shock, 7 patients (11.6%) had pulmonary insufficiency, and 1 patient (1.6%) had hemorrhagic shock, all patients required either venous-arterial (VA) (n = 53, 88.3%), venous-venous (VV) (n = 5, 8.3%) or venous-arterial-venous (VAV) (n = 2, 3.3%) ECMO for hemodynamic support. ECMO parameters were analyzed and common postoperative complications were examined in the setting of survival with comorbidities. RESULTS: In-hospital mortality was 60.7% (n = 37). Patients who survived were younger (52 ± 3.3 vs 66 ± 1.5, p < 0.001) with longer hospital stays (35 ± 4.0 vs 20 ± 1.5, p < 0.03). Survivors required fewer blood products (13 ± 2.3 vs 25 ± 2.3, p = 0.02) with a net negative fluid balance (- 3.5 ± 1.6 vs 3.4 ± 1.6, p = 0.01). Cardiac re-operations worsened survival. CONCLUSION: ECMO is a viable rescue strategy for cardiac surgery patients with a 40% survival to discharge rate. Careful attention to volume management and blood transfusion are important markers for potential survival.

Acute Myeloid Leukemia Presenting Less Than 3 Weeks After Living Donor Kidney Transplant: A Case Report.

Acute myeloid leukemia (AML) is a rare malignancy with increased incidence in the kidney transplantation (KT) population for which immunosuppression has been implicated as a putative cause. The average time interval from KT to AML development is 5 years. We present the case of a 61-year-old man who was found to have peripheral blood blasts on a postoperative day 20 routine blood draw after an uneventful unrelated living donor kidney transplant. He subsequently had a bone marrow biopsy and next-generation sequencing (NGS)-based molecular testing, which demonstrated AML characterized by SMC1A and TET2 mutations. He received induction chemotherapy followed by hematopoietic cell transplantation (HCT) from the kidney donor, who happened to be matched at one haplotype. At 12 months after his HCT and 15 months after his KT, his AML remained in remission, normal renal function was preserved, no active graft-versus-host disease was present, and immunosuppression was tapering. With full donor-derived hematopoietic chimerism, we expect to be able to discontinue immunosuppression shortly, thereby achieving tolerance. The short time interval between KT and development of AML suggests the malignancy was likely present before KT. Modern NGS-based analysis offers a promising method of identifying transplant candidates with unexplained hematologic abnormalities on pre-KT testing who may benefit from formal hematologic evaluation.

Comparative sequence and structure analysis of eIF1A and eIF1AD.

BACKGROUND: Eukaryotic translation initiation factor 1A (eIF1A) is universally conserved in all organisms. It has multiple functions in translation initiation, including assembly of the ribosomal pre-initiation complexes, mRNA binding, scanning, and ribosomal subunit joining. eIF1A binds directly to the small ribosomal subunit, as well as to several other translation initiation factors. The structure of an eIF1A homolog, the eIF1A domain-containing protein (eIF1AD) was recently determined but its biological functions are unknown. Since eIF1AD has a known structure, as well as a homolog, whose structure and functions have been extensively studied, it is a very attractive target for sequence and structure analysis. RESULTS: Structure/sequence analysis of eIF1AD found significant conservation in the surfaces corresponding to the ribosome-binding surfaces of its paralog eIF1A, including a nearly invariant surface-exposed tryptophan residue, which plays an important role in the interaction of eIF1A with the ribosome. These results indicate that eIF1AD may bind to the ribosome, similar to its paralog eIF1A, and could have roles in ribosome biogenenesis or regulation of translation. We identified conserved surfaces and sequence motifs in the folded domain as well as the C-terminal tail of eIF1AD, which are likely protein-protein interaction sites. The roles of these regions for eIF1AD function remain to be determined. We have also identified a set of trypanosomatid-specific surface determinants in eIF1A that could be a promising target for development of treatments against these parasites. CONCLUSIONS: The results described here identify regions in eIF1A and eIF1AD that are likely to play major functional roles and are promising therapeutic targets. Our findings and hypotheses will promote new research and help elucidate the functions of eIF1AD.

Selective Nonoperative Management of Abdominal Gunshot Wounds from Heresy to Adoption: A Multicenter Study of the Research Consortium of New England Centers for Trauma (ReCoNECT).

BACKGROUND: Selective nonoperative management (SNOM) of abdominal gunshot wounds is being practiced in certain trauma centers, but its broader acceptance in the surgical community is unknown. We hypothesized that SNOM has been adopted in New England as an acceptable method of abdominal gunshot wound management. STUDY DESIGN: We reviewed the medical records of abdominal gunshot wound patients admitted from January 1996 to June 2015, in 10 New England Level I and II trauma centers. Outcomes included the incidence, success, and failure of SNOM, and morbidity and mortality related to SNOM. RESULTS: Of 922 patients, 707 (77%) received immediate laparotomy (IMMLAP) and 215 (23%) were managed by SNOM. Compared with IMMLAP patients, those with SNOM had a lower median Injury Severity Score (16 vs 8; p < 0.001), lower incidence of complications (34.7% vs 8.5%; p < 0.001) and mortality (5.2% vs 0.5%; p = 0.002), and shorter ICU and hospital stays (median days 1 of 8 vs 0 of 2, respectively; p < 0.001). One SNOM patient died after 3 days due to a gunshot wound to the head. The overall incidence of SNOM increased from 18% before 2010 to 27% in the following years (p = 0.001). Eighteen patients (8.4%) had unsuccessful SNOM and underwent delayed laparotomy at an average of 12.5 hours (range 141 minutes to 48 hours) after arrival. Nine of them (4.2%) experienced complications that were not directly related to the delayed laparotomy, and none died. The rate of nontherapeutic laparotomies was 14.7% among IMMLAP and 5.5% among delayed laparotomy patients (p = 0.49). CONCLUSIONS: Selective nonoperative management of abdominal gunshot wounds, despite being a heresy only a few years ago, has now been established as an acceptable method of management in Level I and II trauma centers in New England.

eIF1A/eIF5B interaction network and its functions in translation initiation complex assembly and remodeling.

Eukaryotic translation initiation is a highly regulated process involving multiple steps, from 43S pre-initiation complex (PIC) assembly, to ribosomal subunit joining. Subunit joining is controlled by the G-protein eukaryotic translation initiation factor 5B (eIF5B). Another protein, eIF1A, is involved in virtually all steps, including subunit joining. The intrinsically disordered eIF1A C-terminal tail (eIF1A-CTT) binds to eIF5B Domain-4 (eIF5B-D4). The ribosomal complex undergoes conformational rearrangements at every step of translation initiation; however, the underlying molecular mechanisms are poorly understood. Here we report three novel interactions involving eIF5B and eIF1A: (i) a second binding interface between eIF5B and eIF1A; (ii) a dynamic intramolecular interaction in eIF1A between the folded domain and eIF1A-CTT; and (iii) an intramolecular interaction between eIF5B-D3 and -D4. The intramolecular interactions within eIF1A and eIF5B interfere with one or both eIF5B/eIF1A contact interfaces, but are disrupted on the ribosome at different stages of translation initiation. Therefore, our results indicate that the interactions between eIF1A and eIF5B are being continuously rearranged during translation initiation. We present a model how the dynamic eIF1A/eIF5B interaction network can promote remodeling of the translation initiation complexes, and the roles in the process played by intrinsically disordered protein segments.

Head and neck squamous cell cancer (stages III and IV) induction chemotherapy assessment: value of FDG volumetric imaging parameters.

INTRODUCTION: To evaluate whether the change in the metabolic tumour volume (MTV) or total lesion glycolysis (TLG) of the primary tumour, before and after induction chemotherapy, predicts outcome for patients with advanced head and neck squamous cell cancer (SCC). METHODS: Twenty-eight patients with advanced (American Joint Committee on Cancer stage III and IV) head and neck SCC who underwent positron emission tomography (PET)/CT were included in this retrospective study. Primary tumour MTV and TLG were measured using gradient and fixed percentage threshold segmentations. Outcome endpoint was disease progression or mortality. Pearson correlation, Bland-Altman and receiver operator characteristic analysis were performed. RESULTS: The Pearson's correlation coefficients between percentage changes (pre- and post-induction chemotherapy) from gradient MTV (MTVG) and the 38% SUVmax threshold MTV (MTV38) was 0.96 and between MTVG and the 50% threshold MTV (MTV50) was 0.95 (P < 0.0001). The corresponding Pearson r between TLGG and TLG38 was 0.94 and between TLGG and TLG50 was 0.96 (P < 0.0001). The least bias was 1.89% (standard deviation = 25.30%) between the percentage changes of MTVG and MTV50. The areas under the curve for predicting progression or mortality were 0.76 (P = 0.03) for MTVG and 0.82 for TLGG (P = 0.009). Optimum cut points of a 42% reduction in MTVG and a 55% reduction in the TLGG predict event-free survival with a sensitivity of 62.5% and a specificity of 90% and a hazards ratio of 6.25. CONCLUSION: A reduction in primary tumour MTV of at least 42% or in TLG of at least 55% after induction chemotherapy may predict event-free survival in patients with advanced head and neck SCC.