Unusual Presentation of a Granulocytic Sarcoma.

A granulocytic sarcoma is an unusual tumor outside of bone marrow. It is composed of immature cells of the granulocytic cell line. We present a rare case of a 76-year-old male with a history of myelodysplastic syndrome who presented with a large bowel obstruction secondary to lesions at the cecum and transverse colon. He underwent exploratory laparotomy with extended right hemicolectomy. A pathological examination confirmed a granulocytic sarcoma as the cause of the obstruction.

The Statewide Epidemiology of Mucormycosis Among Trauma Patients in Florida.

OBJECTIVES: Mucormycosis is a rare angioinvasive infection caused by filamentous fungi with a high lethality among the immunocompromised. In healthy people, the innate immune system is sufficient to prevent infection. The exception to this is deep tissue exposure seen during trauma. The purpose of this study is to evaluate the epidemiology of mucormycosis using a statewide population-based data set. METHODS: This is a retrospective cohort study of all hospital admissions for mucormycosis within the state of Florida from 1997 through the beginning of 2020. A distribution map was created to evaluate for geographic variation. Botanical growth zones, based on plant hardiness, used by state environmental agencies and landscapers were also used to detect possible patterns based on climate conditions throughout Florida. A multivariable regression analysis was performed to account for confounders and limit bias. RESULTS: A total of 1190 patients were identified for mucormycosis infection. Only 86 of these patients were admitted for trauma. Cutaneous infections were more prevalent among trauma patients while non-trauma patients had more pulmonary infections (P = .04). Trauma patients with infection tended to be younger and less likely to suffer from comorbidities such as immunosuppression (36% vs 46%, P = .07) and diabetes (22.1% vs 47.1%, P ≤ .0001) as compared to their non-trauma counterparts. Mortality was similar with 17.8% for non-trauma patients and 15.1% for traumatized patients (AOR .80 [.42, 1.52]). Length of stay was longer for trauma patients (37.3 vs 23.0, P < .0001). Infections were less prominent in plant hardiness Zone 9 and Zone 10 as compared to Zone 8 (AOR .71 [.61, .82]; AOR .54 [.46, .64], respectively). CONCLUSION: Trauma patients who develop infection from mucormycosis are at high risk of death despite being a younger and healthier population. Mucormycosis infections were primarily soft tissue based among trauma patients. These infections are more prevalent in colder regions within Florida.

Increased Mortality in Hip Fracture Patients With Aortic Stenosis and Pulmonary Hypertension Compared to Aortic Stenosis Alone.

INTRODUCTION: Hip fractures are one of the most common traumatic injuries in the United States, secondary to an aging population. Multiple comorbidities are found in patients who present to trauma centers (TCs) with isolated hip fractures (IHFs) including significant cardiac disease. Aortic stenosis (AS) among these patients has been recently shown to increase mortality. However, factors leading to death from AS are unknown. We hypothesize that pulmonary hypertension (PH) is a significant mechanism of death among IHF patients with AS. METHODS: This is a multicenter retrospective cohort study examining IHF patients treated at Level I and II TCs within a large hospital system from 2015 to 2019. Patients who had IHFs and AS were compared to those who had IHFs, AS, and PH. Multivariable logistic regression was used to risk adjust by age, race, insurance status, and comorbidities. The primary outcome was inpatient mortality. The secondary outcomes were hospital-acquired complications. RESULTS: A total of 1388 IHF patients with AS were included in the study. Eleven percent of these patients also had PH. The crude mortality rate was higher if IHF patients had both AS and PH compared to IHF with AS alone (9% vs 3.7%, P-value .003). After risk adjustment, a higher risk of mortality was still significant (aOR 2.56 [95% CI 1.28, 5.11]). In addition, IHF patients with both AS and PH had higher complication rates; the exposure group had higher percentage of pulmonary embolism (1.4% vs .2%, adjusted P-value .03), new-onset congestive heart failure (4.1% vs 1%, adjusted P-value .01), and sepsis/septicemia (3.5% vs 1.4%, adjusted P-value .05). CONCLUSION: In patients with IHFs, PH and AS increase the likelihood of inpatient mortality by 2.5 times compared to AS alone. Pulmonary hypertension among IHF patients with AS is an important risk factor to identify in the preoperative period. Early identification may lead to better perioperative management and counseling of patients at higher risk of complications.

Practice Patterns of Transesophageal Echocardiography Use Among Trauma Patients: A Multi-Institutional Retrospective Study.

Transesophageal echocardiography (TEE) can be utilized for hemodynamic monitoring and resuscitation. In order to study the pattern of TEE use in trauma patients, a multi-institutional retrospective cohort study was performed comparing adult trauma patients who underwent TEE or those who underwent traditional invasive hemodynamic monitoring (TIHM). TIHM was defined as the use of arterial line, central venous line, or pulmonary artery catheter without TEE. Mortality rates were obtained and multivariable logistic regression was used to risk adjust for age, gender, race, insurance status, Glasgow coma scale (GCS), ICD Injury severity score (ICISS). Compared to TIHM group, more patients in TEE group had a history of congestive heart failure (CHF) or chronic pulmonary disease (CPD). Mortality rate was lower in the TEE group 7 versus 23% (P-value < .0001). After adjusting for GCS and ICISS in multivariable analysis, inpatient mortality was significantly lower in the TEE cohort.

Frailty Score as a Predictor of Outcomes in Geriatric Patients with Isolated Hip Fractures.

BACKGROUND: Isolated hip fractures (IHFs) are a cause of morbidity and mortality in the geriatric population aged >65 years. Frailty has been identified as a determinant for patient outcomes in other surgical specialties. The purpose of this study is to determine if frailty severity is a predictor of outcomes in IHF in the geriatric population. METHODS: This is a retrospective study in a state and ACS Level 2 trauma center. Patients with IHF were reviewed between January 2018 and January 2020. Primary outcome was in-patient mortality. Secondary outcomes include perioperative outcome measures such as UTI, HCAP, DVT, readmission, length of stay, ICU length of stay, nutritional status, and discharge destination. Patients were stratified into mild (1-2), moderate (3-5), and severe (5-7) frailty using the Rockwood Frailty Score (RFS). Clinical characteristics and outcomes were analyzed. RESULTS: We identified 470 patients with IHF who were stratified by mild (N=316), moderate (N-123), and severe (N=31) frailty. Frailty worsened with increasing age (P < .0001). Those who were less frail were more likely discharged home (P < .04). Severely frail patients were more likely discharged to hospice (P < .01). Severely frail patients also were more likely to develop DVT (P < .04) and have poorer nutritional status (P < .02). There were no differences among groups for in-patient mortality. CONCLUSION: Severely frail patients are more likely to be malnourished at baseline and be discharged to hospice care. The RFS is a reliable objective tool to identify high-risk patients and guide goals of care discussion for operative intervention in isolated traumatic hip fractures.

An Early Case of Fat Embolism Syndrome Occurring Following Polytrauma.

Fat embolism syndrome (FES) is a clinical entity occurring due to the presence of fat particles in the microcirculation, typically manifesting 12-72 hours after long bone trauma with respiratory distress, altered mental status, and petechial rash. Our case is that of a 17-year-old girl who suffered multiple orthopedic injuries without intracranial trauma after being a pedestrian struck by a vehicle. Despite presenting with a normal Glasgow Coma Score (GCS), within 4 hours of presentation, she was noted to have an acute mental status change to a GCS 7 with a normal computed tomography brain. Magnetic resonance imaging of the brain was suggestive of FES which, in this patient, had a rapidly progressing course with the development of severe cerebral edema and intracranial hypertension refractory to maximal medical therapy. Our patient required bilateral craniectomies for intracranial decompression and progressed over a 2-month hospital course to have subsequent cranioplasty and functional neurologic improvement. FES requires a high index of clinical suspicion in the presence of long bone fracture with unexplained altered mental status. The clinical course can be rapidly progressing with the development of intracranial hypertension which may benefit from surgical decompression with optimistic prognosis.

Statewide Seasonal Variations of Infections Within the Intensive Care Unit Among the Trauma Population.

BACKGROUND: Infections within intensive care unit (ICU) are a persistent problem among the critically ill. Viral pneumonias have already been established as having a season variations. We attempt to evaluate the seasonal variations of pneumonia among the traumatically injured and the critically ill. MATERIALS AND METHODS: A retrospective cohort study among traumatized patients admitted from 1997 to 2017 to an ICU within the state of Florida was performed who were diagnosed with pneumonia. A multivariate regression analysis was performed to adjust for confounders. Time periods were divided into seasons: summer, winter, spring, and fall. A subset analysis of geriatric patients (>65 years) was also performed. RESULTS: A total of 869 553 patients were identified. The most common viral infection was influenza with adenovirus the least. The most common bacterial pneumonia was Staphylococcus aureus with Bordetella pertussis the least. Pneumonias had a seasonal variation. Compared to summer, winter had a higher likelihood of pneumonia overall (Adjusted Odds Ratio (AOR)1.13). This was seen in the spring (AOR 1.04) but not in fall (AOR 1.00). Viral infections were more pronounced (AOR 3.79) in all other seasons, while bacterial showed increased likelihood during winter (AOR 1.05). In geriatrics, pneumonia was again more likely in the winter (AOR 1.22) with both viral and bacterial infections being more pronounced during winter (AOR 4.79, AOR 1.09). DISCUSSION: Pneumonias are seen more frequently within the ICU during the winter for the traumatized patient. This held true with the critically ill geriatric population as well. This effect was observed in both viral and bacterial pneumonias.

Optimizing energy expenditure and oxygenation toward ventilator tolerance is associated with lower ventilator and intensive care unit days.

BACKGROUND: We hypothesize that if both energy expenditure and oxygenation are optimized (EEOO) toward ventilator tolerance, this would provide patients with the best condition to be liberated from the ventilator. We defined ventilator tolerance as having a respiratory quotient value between 0.7 and 1.0 while maintaining saturations above 98% with FIO2 70% or less and a normal respiratory rate without causing disturbances to the patient's pH. METHODS: This is a single-institution prospective cohort study of ventilator dependent patients within a closed trauma intensive care unit (ICU). The study period was over 52 months. A total of 1,090 patients were part of the primary analysis. The test group (EEOO) was compared to a historical cohort, comparing 26 months in each study group. The primary outcome of this study was number of ventilator days. Secondary outcomes included in-hospital mortality, ICU length of stay (LOS), overall hospital length of stay, tracheostomy rates, reintubation rates, and in-hospital complication rates, such as pneumonia and Acute Respiratory Distress Syndrome (ARDS) ARDS. Both descriptive and multivariable regression analyses were performed to compare the effects of the EEOO protocol with our standard protocols alone. RESULTS: The primary outcome of number of ventilator days was significantly shorter the EEOO cohort by nearly 3 days. This was significant even after adjustment for age, sex, race, comorbidities, nutrition type, and injury severity, (4.3 days vs. 7.2 days, p = 0.0001). The EEOO cohort also had significantly lower ICU days, hospital days, and overall complications rates. CONCLUSION: Optimizing the patient's nutritional regimen to ventilator tolerance and optimizing oxygenation by means of targeted pulmonary mechanics and inspired FIO2 may be associated with lower ventilator and ICU days, as well as overall complication rates. LEVEL OF EVIDENCE: Therapeutic, Level IV.

Impaired interleukin-2 synthesis and T cell proliferation following antibody-mediated CD3 and CD2 or CD28 cross-linking in trans: evidence that T cell activation requires the engagement of costimulatory molecules within the immunological synapse.

Although the T cell costimulatory molecules CD2 and CD28 are enriched within the immunological synapse (IS), it has been suggested that costimulatory molecules need not be localized to the contact site between a T cell and an antigen-presenting cell (APC) in order to costimulate T cell activation. To determine whether CD2 or CD28 engagement outside of the IS is sufficient to costimulate T cell activation, we compared mouse T cell responses to anti-CD3 and anti-CD2 monoclonal antibodies (mAbs) or anti-CD3 and anti-CD28 mAbs immobilized on the same, i.e., in cis, or on different, i.e., in trans, 10 micron polystyrene microspheres. In comparison to T cells that were stimulated with co-immobilized anti-CD3 and anti-CD2 or anti-CD28 mAbs, DNA synthesis, interleukin (IL)-2 production, and cellular proliferation were all severely impaired following T cell stimulation with anti-CD3 and anti-CD2 mAbs or anti-CD3 and anti-CD28 mAbs on different microspheres. Deficient cellular proliferation and IL-2 synthesis by T cells that experienced CD3 and CD2 or CD28 cross-linking in trans provides evidence that costimulatory molecules must function in the context of the IS for optimal T cell activation.

CD2-CD48 interactions promote interleukin-2 and interferon-gamma synthesis by stabilizing cytokine mRNA.

CD2-CD48 interactions enhance T cell receptor-driven mouse T lymphocyte activation. However, the mechanism is not well understood. Here we show that blockade of CD2-CD48 interactions with anti-CD48 monoclonal antibody (mAb) inhibited interleukin (IL)-2 and interferon (IFN)-gamma expression, as well as T cell proliferation in response to mitogenic anti-CD3 mAb, although more potent inhibition resulted from blocking CD28-CD80/CD86 interactions. Blockade of both CD2 and CD28 costimulation abrogated T cell proliferation and cytokine synthesis. Conversely, T cells stimulated with immobilized anti-CD3 and anti-CD2 mAb exhibited increased proliferation and IL-2 and IFN-gamma expression, although a stronger enhancing effect was obtained with immobilized anti-CD3 and anti-CD28 mAb. Concurrent CD2 and CD28 costimulation caused a further increase in proliferation and cytokine synthesis. Stimulation of purified T cells with microsphere-immobilized anti-CD3 and anti-CD2 mAb increased IL-2 and IFN-gamma mRNA stability. However, CD28 costimulation had a stronger enhancing effect on IL-2 and IFN-gamma mRNA stability that was not further increased by concomitant CD2 signaling. CD2, therefore, costimulates T cell activation by stabilizing cytokine mRNA transcripts, albeit with less efficiency than CD28.

Ryanodine receptor signaling is required for anti-CD3-induced T cell proliferation, interleukin-2 synthesis, and interleukin-2 receptor signaling.

Ryanodine receptors (RyR) are involved in regulating intracellular Ca(++) mobilization in T lymphocytes. However, the importance of RyR signaling during T cell activation has not yet been determined. In this study, we have used the RyR-selective antagonists, ruthenium red and dantrolene, to determine the effect of RyR blockade on T cell receptor-mediated activation events and cytokine-dependent T cell proliferation. Both ruthenium red and dantrolene inhibited DNA synthesis and cell division, as well as the synthesis of interleukin (IL)-2 by T lymphocytes responding to mitogenic anti-CD3 antibody. Blockade of RyR at initiation of culture or as late as 24 h after T cell receptor stimulation inhibited T cell proliferation, suggesting a requirement for sustained RyR signaling during cell cycle progression. Although flow cytometry revealed that RyR blockade had little effect on activation-induced expression of the alpha chain (CD25) of the high affinity IL-2 receptor, the inhibitory effect of RyR antagonists could not be reversed by the addition of exogenous IL-2 at initiation of culture. In addition, both ruthenium red and dantrolene had a strong inhibitory effect on IL-2-dependent proliferation of CTLL-2 T cells. These data indicate that RyR are involved in regulating IL-2 receptor signaling that drives T cell progression through the cell cycle. We conclude that RyR-associated Ca(++) signaling regulates T cell proliferation by promoting both IL-2 synthesis and IL-2-dependent cell cycle progression.

Adenosine inhibits activation-induced T cell expression of CD2 and CD28 co-stimulatory molecules: role of interleukin-2 and cyclic AMP signaling pathways.

Adenosine is an immunosuppressive molecule that is associated with the microenvironment of solid tumors. Mouse T cells activated with anti-CD3 antibody in the presence of adenosine with or without coformycin (to prevent adenosine breakdown by adenosine deaminase) exhibited decreased tyrosine phosphorylation of some intracellular proteins and were inhibited in their ability to proliferate and synthesize interleukin (IL)-2. In addition, adenosine interfered with activation-induced expression of the co-stimulatory molecules CD2 and CD28. Activation-induced CD2 and CD28 expression was also diminished when T cells were activated in the presence of anti-IL-2 and anti-CD25 antibodies to neutralize IL-2 bioactivity. Collectively, these data suggest that CD2 and CD28 up-regulation following T cell activation is IL-2-dependent; and that adenosine inhibits activation-induced T cell expression of CD2 and CD28 by interfering with IL-2-dependent signaling. The inhibitory effect of adenosine on activation-induced CD2 and CD28 expression could not be attributed to cyclic AMP (cAMP) accumulation resulting from the stimulation of adenylyl cyclase-coupled adenosine receptors, even though cAMP at concentrations much higher than those generated following adenosine stimulation was inhibitory for both CD2 and CD28 expression. We conclude that adenosine interferes with IL-2-dependent T cell expression of co-stimulatory molecules via a mechanism that does not involve the accumulation of intracellular cAMP.

CD2-CD48 interactions promote cytotoxic T lymphocyte induction and function: anti-CD2 and anti-CD48 antibodies impair cytokine synthesis, proliferation, target recognition/adhesion, and cytotoxicity.

The role of CD2 signaling in cytotoxic T lymphocyte (CTL) development was examined by stimulating mouse T cells with anti-CD3 monoclonal antibody (mAb) in the absence or presence of anti-CD2 mAb or anti-CD48 mAb or both. Induction of nonspecific CTL and interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) synthesis were impaired in the absence of CD2-CD48 interactions. Anti-CD2 mAb also inhibited activation-induced expression of the high-affinity IL-2 receptor (IL-2R). In contrast, IFN-gamma receptor (IFNGR) expression was increased in the presence of anti-CD2 mAb. Reduced cytotoxicity by CTL induced in the absence of CD2-CD48 interactions was associated with a diminished ability of CTL to conjugate with target cells and reduced expression of granzyme B and perforin. Anti-CD2 mAb did not affect expression of Fas ligand and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) by anti-CD3-activated T cells. Cytotoxic effector function and granzyme B and perforin expression were rescued when exogenous IL-2 and IFN-gamma were added in combination with anti-CD2 mAb to anti-CD3-activated T cells at initiation of culture. We conclude that CD2-CD48 interactions during T cell activation are critical for the synthesis of sufficient IL-2 and IFN-gamma to drive CD8(+) T cells to differentiate into functional cytotoxic effector cells.