General Surgery Resident Operative Experiences in Solid Organ Injury: An Examination of Case Logs.

BACKGROUND: Non-operative management (NOM) of traumatic solid organ injury (SOI) has become commonplace. This paradigm shift, along with reduced resident work hours, has significantly impacted surgical residents' operative trauma experiences. We examined ongoing changes in residents' operative SOI experience since duty hour restriction implementation, and assessed whether missed operative experiences were gained elsewhere in the resident experience. METHODS: We examined data from American College of Graduate Medical Education case log reports from 2003 to 2018. We collected mean case volumes in the categories of non-operative trauma, trauma laparotomy, and splenic, hepatic, and pancreatic trauma operations; case volumes for comparable non-traumatic solid organ operations were also collected. Solid organ injury operative volumes were compared against non-traumatic cases, and change over time was analyzed. RESULTS: Over the study period, both trauma laparotomies and non-operative traumas increased significantly (P < .001). In contrast, operative volumes for splenic, hepatic, and pancreatic trauma all significantly decreased (P < .001; P = .014; P < .001, respectively). Non-traumatic spleen cases also significantly decreased (P < .001), but liver cases and distal pancreatectomies increased (P < .001; P = .017). Pancreaticoduodenectomies increased, albeit not to a significant degree (P = .052). CONCLUSIONS: Continuing increases in NOM of SOI correlate with declining resident experience with operative solid organ trauma. These decreases can adversely affect residents' technical skills and decision-making, although trends in specific non-traumatic areas may help to mitigate such losses. Further work should determine the impact of these trends on resident competence and autonomy.

Is New York State good at managing hollow viscus injury?

BACKGROUND: There are an estimated 100,000 cases of abdominal injury (ABI) in the USA, annually resulting in over $12 billion in direct medical cost and $18 billion in lost productivity. This study assesses the timeliness, safety, and efficacy of the surgical management of abdominal injuries (ABIs), hollow viscus injuries (HVIs), and colonic injuries (CIs) for patients residing in New York State (NYS). METHODS: Using data from NYS's Statewide Planning and Research Cooperative System (SPARCS), we identified all trauma patients with ABI admitted between 2006 and 2015. We subdivided ABI into HVI and CI using diagnosis and procedure codes and examined processes of care and outcomes adjusting for patient characteristics, injury severity score, structural, and process indicators. RESULTS: We identified 31,043 hospitalized patients with ABI, 71% were incurred from blunt forces. Most patients with ABI (72%) were treated at a Level I/II trauma center (TC) and 7% patients were transferred to Level I/II TC. Failure to be treated at Level I/II TC was associated with 16% increased hazard of death. HVI was diagnosed in 23% of ABI patients (n = 7294); 18% experienced delayed hollow viscus repair (dHVR); dHVR was associated with a 76% increased hazard of death. CI was diagnosed in 9% of ABI patients (n = 2921) and 18% experienced dHVR. Seventy-five percent of CI were repaired primarily (n = 1354). Less than 37% of stomas were reversed by 4 years of index trauma. CONCLUSION: Most abdominal trauma in NYS was caused by motor vehicle accidents, falls, and assault. dHVR and not being treated at Level I/II TC were associated with worse outcomes. More research is needed to reduce under-triage and delays in the operative treatment of blunt abdominal trauma.

A seven-center examination of the relationship between monthly volume and mortality in trauma: a hypothesis-generating study.

INTRODUCTION: The relationship between trauma volumes and patient outcomes continues to be controversial, with limited data available regarding the effect of month-to-month trauma volume variability on clinical results. This study examines the relationship between monthly trauma volume variations and patient mortality at seven Level I Trauma Centers located in the Eastern United States. We hypothesized that higher monthly trauma volumes may be associated with lower corresponding mortality. METHODS: Monthly patient volume data were collected from seven Level I Trauma Centers. Additional information retrieved included monthly mortality, demographics, mean monthly injury severity (ISS), and trauma mechanism (blunt versus penetrating). Mortality was utilized as the primary study outcome. Statistical corrections for mean age, gender distribution, ISS, and mechanism of injury were made using analysis of co-variance (ANCOVA). Center-specific, annually-adjusted median monthly volumes (CSAA-MMV) were calculated to standardize patient volume differences across participating institutions. Statistical significance was set at α < 0.05. RESULTS: A total of 604 months of trauma admissions, encompassing 122,197 patients, were analyzed. Controlling for patient age, gender, ISS, and mechanism of injury, aggregate data suggested that monthly trauma volumes < 100 were associated with significantly greater mortality (3.9%) than months with volumes > 400 (mortality 2.9%, p < 0.01). To account for differences in monthly volumes between centers, as well as for temporal bias associated with potential differences over the entire study duration period, data were normalized using CSAA-MMV as a standardized reference point. Monthly volumes ≤ 33% of the CSAA-MMV were associated with adjusted mortality of 5.0% whereas monthly volumes ≥ 134% CSAA-MMV were associated with adjusted mortality of 2.7% (p < 0.01). CONCLUSIONS: This hypothesis-generating study suggests that greater monthly trauma volumes appear to be associated with lower mortality. In addition, our data also suggest that across all participating centers mortality may be a function of relative month-to-month volume variation. When normalized to institution-specific, annually-adjusted "median" monthly trauma contacts, we show that months with patient volumes ≤ 33% median may be associated with subtly but not negligibly (1.4-2.3%) higher mortality than months with patient volumes ≥ 134% median.

Rickettsiae stimulate dendritic cells through toll-like receptor 4, leading to enhanced NK cell activation in vivo.

Adoptive transfer of Toll-like receptor (TLR) 4-stimulated dendritic cells (DCs) induces protective immunity against an ordinarily lethal rickettsial challenge, but the mechanism underlying this protection remains elusive. Therefore, we sought to determine the importance of TLR4 in early immunity to rickettsiae in vivo, particularly that conferred by TLR4-stimulated DCs. Rickettsial growth proceeded logarithmically in mice lacking TLR4 function, whereas in TLR4-competent mice rickettsial growth manifested a lag phase early, suggesting that TLR4 may initiate innate rickettsial immunity. TLR4-competent mice produced significant amounts of interferon (IFN)-gamma on day 1 of Rickettsia conorii infection, which was associated with significant expansion of the population of activated NK cells. Moreover, NK cells from TLR4-competent mice produced significantly higher levels of IFN-gamma and had greater cytotoxic activity than did those from TLR4-deficient mice. Last, adoptive transfer of rickettsiae-exposed, TLR4-stimulated DCs activated NK cells in vivo. Together, these data reveal an important role for DCs in recognizing rickettsiae through TLR4 and inducing early antirickettsial immunity.

The absence of Toll-like receptor 4 signaling in C3H/HeJ mice predisposes them to overwhelming rickettsial infection and decreased protective Th1 responses.

The importance of toll-like receptor 4 (TLR4) in immunity to rickettsiae remains elusive. To investigate the role of TLR4 in protection against rickettsioses, we utilized C3H/HeJ mice, which are naturally defective in TLR4 signaling, and compared the responses of C3H/HeN and C3H/HeJ mice following intravenous inoculation with Rickettsia conorii. Mice genetically defective in TLR4 signaling developed overwhelming, fatal rickettsial infections when given an inoculum that was nonfatal for TLR4-competent mice. In addition, mice lacking the ability to signal through TLR4 had significantly greater rickettsial burdens in vivo. Moreover, we observed greater concentrations of the cytokines interleukin 6 (IL-6), tumor necrosis factor alpha, IL-12p40, IL-12p70, and IL-17 in the sera of mice with intact TLR4 function as well as significantly greater quantities of activated CD4(+) and CD8(+) T lymphocytes. Additionally, we also observed that Th17 cells were present only in TLR4-competent mice, suggesting an important role for TLR4 ligation in the activation of this subset. In agreement with these data, we also observed significantly greater percentages of immunosuppressive regulatory T cells in the spleen during infection in TLR4-defective mice. Together, these data demonstrate that, while rickettsiae do not contain endotoxic lipopolysaccharide, they nevertheless initiate TLR4-specific immune responses, and these responses are important in protection.

Prior exposure to uninfected mosquitoes enhances mortality in naturally-transmitted West Nile virus infection.

BACKGROUND: The global emergence of West Nile virus (WNV) has highlighted the importance of mosquito-borne viruses. These are inoculated in vector saliva into the vertebrate skin and circulatory system. Arthropod-borne (arbo)viruses such as WNV are transmitted to vertebrates as an infectious mosquito probes the skin for blood, depositing the virus and saliva into the skin and circulation. Growing evidence has demonstrated that arthropod, and recently mosquito, saliva can have a profound effect on pathogen transmission efficiency, pathogenesis, and disease course. A potentially important aspect of natural infections that has been ignored is that in nature vertebrates are typically exposed to the feeding of uninfected mosquitoes prior to the mosquito that transmits WNV. The possibility that pre-exposure to mosquito saliva might modulate WNV infection was explored. PRINCIPAL FINDINGS: Here we report that sensitization to mosquito saliva exacerbates viral infection. Prior exposure of mice to mosquito feeding resulted in increased mortality following WNV infection. This aggravated disease course was associated with enhanced early viral replication, increased interleukin-10 expression, and elevated influx of WNV-susceptible cell types to the inoculation site. This exacerbated disease course was mimicked by passive transfer of mosquito-sensitized serum. SIGNIFICANCE: This is the first report that sensitization to arthropod saliva can exacerbate arthropod-borne infection, contrary to previous studies with parasite and bacteria infections. This research suggests that in addition to the seroreactivity of the host to virus, it is important to take into account the immune response to vector feeding.

Rickettsiae-stimulated dendritic cells mediate protection against lethal rickettsial challenge in an animal model of spotted fever rickettsiosis.

The role played by dendritic cells (DCs), initiators and orchestrators of the immune response, remains unclear in rickettsial infections. To investigate their importance in rickettsioses, we analyzed the responses of murine bone marrow-derived DCs (BMDCs) after rickettsial stimulation in vitro and their protective role in vivo. Rickettsia conorii stimulation of BMDCs caused significant maturation and production of proinflammatory cytokines. Transfer of rickettsiae-stimulated DCs protected mice from lethal rickettsial challenge by limiting rickettsial proliferation in vivo, whereas partial protection was observed in mice receiving lipopolysaccharide (LPS)-stimulated DCs. Immunity to R. conorii after transfer of DCs was associated with up-regulation of CD40, CD80, CD86, and major histocompatibility complex class II; with production of IL-2, IL-12, and IL-23; and with production of antigen-specific interferon- gamma in T cells. Taken together, our data suggest that a vigorous proinflammatory response in DCs is associated with protective immunity to rickettsiae and that generation of antigen-specific immunity is crucial to complete protection.

An intradermal environment promotes a protective type-1 response against lethal systemic monocytotropic ehrlichial infection.

Immune responses against monocytotropic ehrlichiosis during infection with a strain of Ehrlichia from Ixodes ovatus (IOE) were evaluated using a model that closely reproduces the pathology and immunity associated with tick-transmitted human monocytotropic ehrlichiosis. C57BL/6 mice were inoculated intradermally or intraperitoneally with high-dose highly virulent IOE or intraperitoneally with mildly virulent Ehrlichia muris. Intradermal (i.d.) infection with IOE established mild, self-limited disease associated with minimal hepatic apoptosis, and all mice survived past 30 days. Intraperitoneal (i.p.) infection with IOE resulted in acute, severe toxic shock-like syndrome and severe multifocal hepatic apoptosis and necrosis, and all mice succumbed to disease. Compared to i.p. infection with IOE, intradermally infected mice had a 100- to 1,000-fold lower bacterial load in the spleen with limited dissemination. Compared to mice infected intraperitoneally with IOE, i.d. infection stimulated a stronger protective type-1 cell-mediated response on day 7 of infection, characterized by increased percentages of both CD4+ and CD8+ splenic T cells, generation of a greater number of IOE-specific, gamma interferon-producing CD4+ Th1 cells, and higher levels of tumor necrosis factor (TNF-alpha) in the spleen but lower concentrations of serum TNF-alpha and interleukin-10. These data suggest that under the conditions of natural route of challenge (i.e., i.d. inoculation), the immune response has the capacity to confer complete protection against monocytotropic ehrlichiosis, which is associated with a strong cell-mediated type-1 response and decreased systemic production of pro- and anti-inflammatory cytokines.

T cells mediate cross-protective immunity between spotted fever group rickettsiae and typhus group rickettsiae.

Rickettsioses are severe infections caused by obligately intracellular bacteria that preferentially infect the endothelium lining the vasculature. The causative agents, rickettsiae, have been divided according to biological, genetic, and antigenic parameters into 2 main groups: spotted fever and typhus. They have not been thought to stimulate cross-reactive protective immune responses; however, in this study, we show that, in relevant animal models that mimic human rickettsial infections, there is reciprocal immunological cross-protection between spotted fever group and typhus group rickettsiae. Furthermore, we present evidence that T cells are responsible for this cross-immunity and that cross-stimulation of T cells also occurs in humans.

Selective in vivo depletion of CD4(+) T lymphocytes with anti-CD4 monoclonal antibody during acute infection of calves with Anaplasma marginale.

To investigate the in vivo role of CD4(+) T lymphocytes during acute anaplasmosis, thymectomized calves were selectively depleted of CD4(+) T lymphocytes by treatment with anti-CD4 monoclonal antibody (MAb) and were then infected with the Florida strain of Anaplasma marginale in two sequential experiments (experiments 1 and 2). Treatment of thymectomized calves with a total of 5.0 mg of anti-CD4 MAb/kg of body weight during the 1st week followed by 0.3-mg/kg doses administered twice weekly for 7 weeks resulted in significant depletion of CD3(+) CD4(+) and CD4(+) CD45R(+) (naive) T lymphocytes from blood, spleen, and peripheral lymph nodes for the duration of the 8-week study, compared to the results for thymectomized control calves treated with a subclass-matched MAb. All calves became parasitemic and pyretic following experimental infection with A. marginale, and decreases in packed cell volume (PCV) coincided with peak parasitemia. No significant differences in PCV or parasitemia were observed between treatment groups. Thymectomized calves treated with anti-CD4 MAb were able to mount an anti-A. marginale antibody response, although in experiment 2, anti-CD4 MAb-treated calves had four- to sixfold lower immunoglobulin G1 (IgG1) and no detectable IgG2 anti-A. marginale major surface protein 2-specific antibody titers compared to thymectomized control calves treated with a subclass-matched MAb. At the level of CD4(+)-T-lymphocyte depletion achieved and experimental anaplasmosis induced, thymectomized anti-CD4 MAb-treated calves were able to control acute anaplasmosis. This was in contrast to the prediction that significant depletion of CD4(+) T lymphocytes would abrogate resistance to acute infection.