Zachary Bauman

Expression Profiling of Homocysteine Junction Enzymes in the NCI60 Panel of Human Cancer Cell Lines

Methionine metabolism provides two key cellular reagents: S-adenosylmethionine and glutathione, derived from the common intermediate, homocysteine. A majority of cancer cells exhibit a methionine-dependent phenotype whereby they are unable to grow in medium in which methionine is replaced by its precursor, homocysteine. Additionally, CpG island hypermethylation of tumor suppressor gene promoters is observed in a background of global hypomethylation in cancerous cells. In this study, we have profiled the expression levels of the homocysteine junction enzymes, methionine synthase (MS), MS reductase (MSR), and cystathionine beta-synthase (CBS) in the NCI60 panel of cancer cell lines. The doubling time of non-small lung cell cancer lines, which exhibit the lowest levels of MS within the panel, was significantly correlated with expression of MS. The ratio of MS to MSR varied over a 5-fold range in the different cell types, which may modulate methionine synthesis. Interestingly, markedly reduced CBS expression was seen in the methionine-dependent prostate cancer cell line, PC-3, but not in the methionine-independent cell line, DU-145. However, neither provision of the transsulfuration pathway product, cysteine, nor overexpression of CBS rescued the growth impairment, indicating that reduced CBS was not responsible for the methionine-dependent phenotype in this cell line.

Improving mortality in trauma laparotomy through the evolution of damage control resuscitation: Analysis of 1,030 consecutive trauma laparotomies

BACKGROUND The aim of this study was to evaluate the related change in outcomes (mortality, complications) in patients undergoing trauma laparotomy (TL) with the implementation of damage control resuscitation (DCR). We hypothesized that the implementation of DCR in patients undergoing TL is associated with better outcomes. METHODS We analyzed 1,030 consecutive patients with TL. Patients were stratified into three phases: pre-DCR (2006–2007), transient (2008–2009), and post-DCR (2010–2013). Resuscitation fluids (crystalloids and blood products), injury severity score (ISS), vital signs, and laboratory (hemoglobin, international normalized ratio, lactate) parameters were recorded. Regression analysis was performed after adjusting for age, ISS, laboratory and vital parameters, comorbidities, and resuscitation fluids to identify independent predictors for outcomes in each phase. RESULTS Patient demographics and ISS remained the same throughout the three phases. There was a significant reduction in the volume of crystalloid (p = 0.001) and a concomitant increase in the blood product resuscitation (p = 0.04) in the post-DCR phase compared to the pre-DCR and transient DCR phases. Volume of crystalloid resuscitation was an independent predictor of mortality in the pre-DCR (OR [95% CI]: 1.071 [1.03–1.1], p = 0.01) and transient (OR [95% CI]: 1.05 [1.01–1.14], p = 0.01) phases; however, it was not associated with mortality in the post-DCR phase (OR [95% CI]:1.01 [0.96–1.09], p = 0.1). Coagulopathy (p = 0.01) and acidosis (p = 0.02) were independently associated with mortality in all three phases. CONCLUSION The implementation of DCR was associated with improved outcome in patients undergoing TL. There was a decrease in the use of damage control laparotomy, with a decrease in the use of crystalloid and an increase in the use of blood products. LEVEL OF EVIDENCE Prognostic study, level III.

Identifying potential utility of REBOA: An autopsy study

BACKGROUND Resuscitative thoracotomy (RT) has been the standard therapy in patients with acute arrest due to hemorrhagic shock. However, with the development of resuscitative endovascular balloon occlusion of the aorta (REBOA), its role as a potential adjunct to a highly morbid intervention such as RT is being discussed. The aim of this study was to identify patients who most likely would have potentially benefited from REBOA use based on autopsy findings. METHODS We performed a 4-year retrospective review of all RTs performed at our Level I trauma center. Patients with in-hospital mortality and who underwent subsequent autopsies were included. Patients were divided into blunt and penetrating trauma with and without thoracic injuries. Autopsy reports were reviewed to identify vascular and solid organ injuries. Outcome measure was potential benefit with REBOA. Potential benefit with REBOA was defined based on the ability to safely deploy REBOA. In patients without cardiac, aortic, and major pulmonary vasculature injuries, REBOA was considered potentially beneficial. In all other patients, it was considered as nonbeneficial. RESULTS A total of 98 patients underwent an RT, of whom 87 had subsequent autopsies and were reviewed. The mean age was 35.25 (SD, 17.85) years, mean admission systolic blood pressure was 51.38 (SD, 70.11) mm Hg, median Injury Severity Score was 29 (interquartile range [IQR], 25–42), and 44 had penetrating injury. Resuscitative endovascular balloon occlusion of the aorta would have been potentially beneficial in 51.2% of patients (22 of 43 patients) with blunt mechanism of trauma, whereas REBOA would have been potentially beneficial in 38.6% of patients (17 of 44 patients) with penetrating mechanism of trauma. A subgroup analysis showed that REBOA use would have been potentially beneficial in 50.0% of blunt thoracic and 33.3% of penetrating thoracic trauma patients. CONCLUSIONS There are a great enthusiasm and premature efforts to introduce REBOA as an alternative to RT. While there exists a great potential for benefit with REBOA use in the management of noncompressible torso hemorrhage, the current indications for REBOA need to be defined better. Patients with penetrating chest trauma in extremis should be considered an absolute contraindication for REBOA use. The majority of patients with blunt trauma in extremis may potentially benefit from REBOA. However, better criteria will help increase these patients who may potentially benefit from REBOA placement. LEVEL OF EVIDENCE Therapeutic study, level V.

Lung Injury Prediction Score Is Useful in Predicting Acute Respiratory Distress Syndrome and Mortality in Surgical Critical Care Patients

Background. Lung injury prediction score (LIPS) is valuable for early recognition of ventilated patients at high risk for developing acute respiratory distress syndrome (ARDS). This study analyzes the value of LIPS in predicting ARDS and mortality among ventilated surgical patients. Methods. IRB approved, prospective observational study including all ventilated patients admitted to the surgical intensive care unit at a single tertiary center over 6 months. ARDS was defined using the Berlin criteria. LIPS were calculated for all patients and analyzed. Logistic regression models evaluated the ability of LIPS to predict development of ARDS and mortality. A receiver operator characteristic (ROC) curve demonstrated the optimal LIPS value to statistically predict development of ARDS. Results. 268 ventilated patients were observed; 141 developed ARDS and 127 did not. The average LIPS for patients who developed ARDS was 8.8 ± 2.8 versus 5.4 ± 2.8 for those who did not (p < 0.001). An ROC area under the curve of 0.79 demonstrates LIPS is statistically powerful for predicting ARDS development. Furthermore, for every 1-unit increase in LIPS, the odds of developing ARDS increase by 1.50 (p < 0.001) and odds of ICU mortality increase by 1.22 (p < 0.001). Conclusion. LIPS is reliable for predicting development of ARDS and predicting mortality in critically ill surgical patients.

Racial differences in vasopressor requirements for septic shock.

ABSTRACT Objective: The objective of this study was to compare vasopressor requirements between African American (AA) patients and white patients in septic shock. Methods: This was a retrospective cohort review conducted over a 2-year period measuring total and mean dosage of various vasopressors used between two racial groups during the treatment of patients admitted with septic shock. The study included patients admitted to the intensive care unit with septic shock at an 805-bed tertiary, academic center. All septic shock patients were managed with vasopressors. Vasopressor selection, dosage, and duration were at the discretion of the treating physician. Total, mean, and duration of vasopressor dosing requirements were obtained for study participants. Comorbidities, prehospitalization antihypertensive medication requirements, intravenous fluids given during the septic shock phase, and source of infection were analyzed. Results: One hundred fifty-nine patients with septic shock were analyzed, of which 96 (60.4%) were AAs (P < 0.059). African Americans had higher rates of end-stage renal disease and hypertension compared with whites, 85.7% vs. 14.3% (P < 0.011; odds ratio [OR], 15.684) and 68.3% vs. 31.7% (P < 0.007; OR, 3.357), respectively. Norepinephrine (NE) was administered to 150 patients, 57.2% of which were AAs (P < 0.509). Thirteen patients received dopamine (5% AAs, P < 0.588), 40 patients received phenylephrine (15.7% AAs, P < 0.451), and five patients received epinephrine (1.9% AAs, P < 0.660). Comparing vasopressors between races, only NE showed statistical significance via logistic regression modeling for the AA race in terms of total dosage (AAs 736.8 [SD, 897.3] &mgr;g vs. whites 370 [SD, 554.2] &mgr;g, P < 0.003), duration of vasopressor used (AAs 38.38 [SD, 34.75] h vs. whites 29.09 [SD, 27.11] h, P < 0.037), and mean dosage (AAs 21.08 [SD, 22.23] &mgr;g/h vs. whites 12.37 [SD, 13.86] &mgr;g/h, P < 0.01). Mortality between groups was not significant. Logistic regression identified discrepancy of the mean dose NE in AAs compared with whites, with OR of 1.043 (P = 0.01). Conclusions: African American patients with septic shock were treated with higher doses of NE and required longer duration of NE administration compared with white patients.

Pneumoperitoneum as a result of a ruptured splenic abscess

We encountered a case of ruptured splenic abscess presenting as peritonitis and pneumoperitoneum. Our patient did not have an underlying neoplasm nor was she immunosuppressed. In our case, splenectomy was the treatment of choice in combination with antibiotics, which proved to be a good outcome for the patient. Work-up for the cause of the abscess was negative, although bacteria predominately found in the oral flora were isolated from the abscess. We strongly encourage that splenic abscess be considered on the differential diagnosis of patients presenting with pneumoperitoneum and peritonitis, although a clinical rarity.

Gallbladder Volvulus Presenting as Acute Appendicitis

We encountered a case of gallbladder volvulus in an 88-year-old thin female in which the initial presentation was more consistent with that of acute appendicitis. After complete work-up, including physical exam, lab work, and computed tomography, the definite diagnosis of gallbladder volvulus was not made until intraoperative visualization was obtained. Gallbladder volvulus is a rare but serious condition, which requires a high clinical suspicion so prompt surgical intervention can be undertaken.

Canary in the coal mine—Initial reports of thermal injury secondary to electronic cigarettes

The use of electronic cigarettes has become increasingly popular with claims suggesting healthier alternatives to tobacco cigarettes. However, research regarding the safety of such devices has been limited to an analysis of the inhaled vapor and the short and long-term effects on the body. A lesser recognized risk of electronic cigarette use is that of lithium-ion battery failure causing ignition, leading to severe thermal injury. Such incidents have been reported in the media but with inconsistencies from a lack of focus on the injuries sustained and a cause of ignition. The cases presented here are among the first recognized thermal injuries sustained from electronic cigarette lithium-ion battery failure, the potential rationale for these failures, and a need for increased awareness of the safety hazards of these devices.

Advancing Trauma and Emergency Education Through Virtual Presence

Purpose of ReviewTelemedicine has played a pivotal role in centralization of trauma care at large trauma centers and trauma systems. The purpose of this review is to highlight the role of telemedicine and virtual education in advancing trauma and emergency education through virtual presenceRecent FindingsThe use of telemedicine has recently revolutionized trauma patient care and education with the introduction of telepresence. The development of telepresence allows experienced trauma surgeons to have a virtual presence in emergency rooms in some of the most remote locations on the planet, providing up-to-date clinical knowledge and training to surgeons working in a remote area that is otherwise not possible.SummaryThrough this virtual presence, trauma surgeons are able to help direct trauma patient care, advise on diagnostic studies and procedures, and help make appropriate decisions regarding the transfer of trauma patients.

The Combination of Gastroschisis, Jejunal Atresia, and Colonic Atresia in a Newborn.

We encountered a rare case of gastroschisis associated with jejunal atresia and colonic atresia. In our case, the jejunal atresia was not discovered for 27 days after the initial abdominal wall closure. The colonic atresia was not discovered for 48 days after initial repair of the gastroschisis secondary to the rarity of the disorder. Both types of atresia were repaired with primary hand-sewn anastomoses. Other than the prolonged parenteral nutrition and hyperbilirubinemia, our patient did very well throughout his hospital course. Based on our case presentation, small bowel atresia and colonic atresia must be considered in patients who undergo abdominal wall closure for gastroschisis with prolonged symptoms suggestive of bowel obstruction. Our case report also demonstrates primary enteric anastomosis as a safe, well-tolerated surgical option for patients with types of intestinal atresia.