Gabriel Brat

Use of National Burden to Define Operative Emergency General Surgery.

IMPORTANCE Emergency general surgery (EGS) represents 11% of surgical admissions and 50% of surgical mortality in the United States. However, there is currently no established definition of the EGS procedures. OBJECTIVE To define a set of procedures accounting for at least 80% of the national burden of operative EGS. DESIGN, SETTING, AND PARTICIPANTS A retrospective review was conducted using data from the 2008-2011 National Inpatient Sample. Adults (age, ≥18 years) with primary EGS diagnoses consistent with the American Association for the Surgery of Trauma definition, admitted urgently or emergently, who underwent an operative procedure within 2 days of admission were included in the analyses. Procedures were ranked to account for national mortality and complication burden. Among ranked procedures, contributions to total EGS frequency, mortality, and hospital costs were assessed. The data query and analysis were performed between November 15, 2015, and February 16, 2016. MAIN OUTCOMES AND MEASURES Overall procedure frequency, in-hospital mortality, major complications, and inpatient costs calculated per 3-digit International Classification of Diseases, Ninth Revision, Clinical Modification procedure codes. RESULTS The study identified 421 476 patient encounters associated with operative EGS, weighted to represent 2.1 million nationally over the 4-year study period. The overall mortality rate was 1.23% (95% CI, 1.18%-1.28%), the complication rate was 15.0% (95% CI, 14.6%-15.3%), and mean cost per admission was

A multiphase transitioning peptide hydrogel for suturing ultrasmall vessels

13 241 (95% CI,

Mesenchymal Stem Cells Enhance Nerve Regeneration in a Rat Sciatic Nerve Repair and Hindlimb Transplant Model

12 957-

The truth about trauma readmissions.

13 525). After ranking the 35 procedure groups by contribution to EGS mortality and morbidity burden, a final set of 7 operative EGS procedures were identified, which collectively accounted for 80.0% of procedures, 80.3% of deaths, 78.9% of complications, and 80.2% of inpatient costs nationwide. These 7 procedures included partial colectomy, small-bowel resection, cholecystectomy, operative management of peptic ulcer disease, lysis of peritoneal adhesions, appendectomy, and laparotomy. CONCLUSIONS AND RELEVANCE Only 7 procedures account for most admissions, deaths, complications, and inpatient costs attributable to the 512 079 EGS procedures performed in the United States each year. National quality benchmarks and cost reduction efforts should focus on these common, complicated, and costly EGS procedures.

Postsurgical prescriptions for opioid naive patients and association with overdose and misuse: retrospective cohort study

Many surgeries are complicated by the need to anastomose, or reconnect, micron-scale vessels. Although suturing remains the gold standard for anastomosing vessels, it is difficult to place sutures correctly through collapsed lumen, making the procedure prone to failure. Here, we report a multi-phase transitioning peptide hydrogel that can be injected into the lumen of vessels to facilitate suturing. The peptide, which contains a photocaged glutamic acid, forms a solid-like gel in a syringe and can be shear-thin delivered to the lumen of collapsed vessels (where it distends the vessel), and the space between two vessels (where it is used to approximate the vessel ends). Suturing is performed directly through the gel. Light is used to initiate the final gel-sol phase transition that disrupts the hydrogel network, allowing the gel to be removed and blood flow to resume. This gel adds a new tool to the armamentarium for micro- and supermicrosurgical procedures.

Near-infrared lymphography as a minimally invasive modality for imaging lymphatic reconstitution in a rat orthotopic hind limb transplantation model

This study investigates the efficacy of local and intravenous mesenchymal stem cell (MSC) administration to augment neuroregeneration in both a sciatic nerve cut-and-repair and rat hindlimb transplant model. Bone marrow-derived MSCs were harvested and purified from Brown-Norway (BN) rats. Sciatic nerve transections and repairs were performed in three groups of Lewis (LEW) rats: negative controls (n = 4), local MSCs (epineural) injection (n = 4), and systemic MSCs (intravenous) injection (n = 4). Syngeneic (LEW-LEW) (n = 4) and allogeneic (BN-LEW) (n = 4) hindlimb transplants were performed and assessed for neuroregeneration after local or systemic MSC treatment. Rats undergoing sciatic nerve cut-and-repair and treated with either local or systemic injection of MSCs had significant improvement in the speed of recovery of compound muscle action potential amplitudes and axon counts when compared with negative controls. Similarly, rats undergoing allogeneic hindlimb transplants treated with local injection of MSCs exhibited significantly increased axon counts. Similarly, systemic MSC treatment resulted in improved nerve regeneration following allogeneic hindlimb transplants. Systemic administration had a more pronounced effect on electromotor recovery while local injection was more effective at increasing fiber counts, suggesting different targets of action. Local and systemic MSC injections significantly improve the pace and degree of nerve regeneration after nerve injury and hindlimb transplantation.

Phenotyping the Immune Response to Trauma: A Multiparametric Systems Immunology Approach*

BACKGROUND There is a paucity of data on the causes and associated patient factors for unplanned readmissions among trauma patients. METHODS We examined patients admitted for traumatic injuries between 2007 and 2011 in the California State Inpatient Database. Using chi-square tests and multivariate logistic regression models, we determined rates, reasons, locations, and patient factors associated with 30-day readmissions. RESULTS Among 252,752 trauma discharges, the overall readmission rate was 7.56%, with 36% of readmissions occurring at a hospital different from the hospital of initial admission. Predictors of readmissions included being discharged against medical advice (odds ratio [OR]: 2.56 [2.35 to 2.76]); Charlson scores ≥2 (OR: 2.00 [1.91 to 2.10]); and age ≥45 years (OR: 1.29 [1.25 to 1.33]). Major reasons for readmissions were musculoskeletal complaints (22.29%), psychiatric conditions (9.40%), and surgical infections (6.69%). CONCLUSIONS Health and social vulnerabilities influence readmission among trauma patients, with many readmitted at other hospitals. Targeted interventions among high-risk patients may reduce readmissions after traumatic injuries.

Impact of Managed Care on Publicly Insured Children with Special Health Care Needs

Abstract Objective To quantify the effects of varying opioid prescribing patterns after surgery on dependence, overdose, or abuse in an opioid naive population. Design Retrospective cohort study. Setting Surgical claims from a linked medical and pharmacy administrative database of 37 651 619 commercially insured patients between 2008 and 2016. Participants 1 015 116 opioid naive patients undergoing surgery. Main outcome measures Use of oral opioids after discharge as defined by refills and total dosage and duration of use. The primary outcome was a composite of misuse identified by a diagnostic code for opioid dependence, abuse, or overdose. Results 568 612 (56.0%) patients received postoperative opioids, and a code for abuse was identified for 5906 patients (0.6%, 183 per 100 000 person years). Total duration of opioid use was the strongest predictor of misuse, with each refill and additional week of opioid use associated with an adjusted increase in the rate of misuse of 44.0% (95% confidence interval 40.8% to 47.2%, P<0.001), and 19.9% increase in hazard (18.5% to 21.4%, P<0.001), respectively. Conclusions Each refill and week of opioid prescription is associated with a large increase in opioid misuse among opioid naive patients. The data from this study suggest that duration of the prescription rather than dosage is more strongly associated with ultimate misuse in the early postsurgical period. The analysis quantifies the association of prescribing choices on opioid misuse and identifies levers for possible impact.

Whatever happens to trauma patients who leave against medical advice

Wider application of vascularized composite allotransplantation (VCA) is limited by the need for chronic immunosuppression. Recent data suggest that the lymphatic system plays an important role in mediating rejection. This study used near‐infrared (NIR) lymphography to describe lymphatic reconstitution in a rat VCA model. Syngeneic (Lewis–Lewis) and allogeneic (Brown Norway–Lewis) rat orthotopic hind limb transplants were performed without immunosuppression. Animals were imaged pre‐ and postoperatively using indocyanine green (ICG) lymphography. Images were collected using an NIR imaging system. Co‐localization was achieved through use of an acrylic paint/hydrogen peroxide mixture. In all transplants, ICG first crossed graft suture lines on postoperative day (POD) 5. Clinical signs of rejection also appeared on POD 5 in allogeneic transplants, with most exhibiting Grade 3 rejection by POD 6. Injection of an acrylic paint/hydrogen peroxide mixture on POD 5 confirmed the existence of continuous lymphatic vessels crossing the suture line and draining into the inguinal lymph node. NIR lymphography is a minimally invasive imaging modality that can be used to study lymphatic vessels in a rat VCA model. In allogeneic transplants, lymphatic reconstitution correlated with clinical rejection. Lymphatic reconstitution may represent an early target for immunomodulation.

Intraductal Papillary Mucinous Neoplasm of the Liver: GI Image

Objective: Trauma induces a complex immune response that requires a systems biology research approach. Here, we used a novel technology, mass cytometry by time-of-flight, to comprehensively characterize the multicellular response to trauma. Design: Peripheral blood mononuclear cells samples were stained with a 38-marker immunophenotyping cytometry by time-of-flight panel. Separately, matched peripheral blood mononuclear cells were stimulated in vitro with heat-killed Streptococcus pneumoniae or CD3/CD28 antibodies and stained with a 38-marker cytokine panel. Monocytes were studied for phagocytosis and oxidative burst. Setting: Single-institution level 1 trauma center. Patients or Subjects: Trauma patients with injury severity scores greater than 20 (n = 10) at days 1, 3, and 5 after injury, and age- and gender-matched controls. Interventions: None. Measurements and Main Results: Trauma-induced expansion of Th17-type CD4+ T cells was seen with increased expression of interleukin-17 and interleukin-22 by day 5 after injury. Natural killer cells showed reduced T-bet expression at day 1 with an associated decrease in tumor necrosis factor-&bgr;, interferon-&ggr;, and monocyte chemoattractant protein-1. Monocytes showed robust expansion following trauma but displayed decreased stimulated proinflammatory cytokine production and significantly reduced human leukocyte antigen - antigen D related expression. Further analysis of trauma-induced monocytes indicated that phagocytosis was no different from controls. However, monocyte oxidative burst after stimulation increased significantly after injury. Conclusions: Using cytometry by time-of-flight, we were able to identify several major time-dependent phenotypic changes in blood immune cell subsets that occur following trauma, including induction of Th17-type CD4+ T cells, reduced T-bet expression by natural killer cells, and expansion of blood monocytes with less proinflammatory cytokine response to bacterial stimulation and less human leukocyte antigen - antigen D related. We hypothesized that monocyte function might be suppressed after injury. However, monocyte phagocytosis was normal and oxidative burst was augmented, suggesting that their innate antimicrobial functions were preserved. Future studies will better characterize the cell subsets identified as being significantly altered by trauma using cytometry by time-of-flight, RNAseq technology, and functional studies.