Surgical Critical Care for the Trauma Patient with Cardiac Disease.

The elderly population is rapidly increasing in number. Therefore, geriatric trauma is becoming more prevalent. All practitioners caring for geriatric trauma patients should be familiar with the structural and functional changes naturally occurring in the aging heart, as well as common preexisting cardiac diseases in the geriatric population. Identification of the shock state related to cardiac dysfunction and targeted assessment of perfusion and resuscitation are important when managing elderly patients. Finally, management of cardiac dysfunction in the trauma patient includes an appreciation of the inherent effects of trauma on cardiac function.

Assessing patient-caregiver communication in cancer--a psychometric validation of the Cancer Communication Assessment Tool (CCAT-PF) in a German sample.

PURPOSE: The recently introduced Cancer Communication Assessment Tool (CCAT-PF) measures congruence in patient-caregiver communication and was initially validated in lung cancer patients. Contributing to a greater proportion of the variance in the conflict scores, primary caregivers were hypothesized to experience greater stress. For a detailed understanding of conflicting communication patterns of cancer-affected families, our study aimed for psychometric validation of the CCAT-PF in a sample covering heterogeneous tumor entities. METHODS: Subsequent to a cross-sectional survey of 189 pairs of cancer patients (31 % gastrointestinal, 34 % lung, and 35 % urological) and their caregivers' exploratory factor analysis with principal component condensation and varimax rotation was conducted (response rate, 74.2 %). Reliability and construct validity were assessed calculating Cronbach's α and Pearson correlation coefficients for CCAT-P and CCAT-F scales and related constructs, respectively. RESULTS: Cancer-related communication according to the CCAT-PF can be subdivided into four factors including the scales Disclosure, Limitation of treatment, Family involvement in treatment decisions, and Continuing treatment. Reliability ranged from α = .51-.68. The Disclosure scale, describing poor cancer-related communication of the patient, was correlated with patient's distress (QSC-R10: r = .30, p < .0001), unmet needs in several areas (SCNS-SF-34: r = .25-.32, p < .001), and negatively with social/family well-being (FACT: r = -0.31, p < .0001). Higher scores on the scale were significantly associated with considerable decrements in emotional well-being especially for caregivers perceiving patients' disclosure as problematic. CONCLUSIONS: The Disclosure scale originating from the CCAT-PF emerged as a short, valid, and reliable stand-alone instrument for identifying conflicting communication in patient-caregiver-dyads at risk.

Humanitarian care by a forward surgical team in afghanistan.

BACKGROUND: The mission of a Forward Surgical Team (FST) is to provide immediate lifesaving surgery to wounded U.S. and coalition forces. The degree of humanitarian surgical care provided to civilians is a topic of controversy. METHODS: From May 2011 to November 2011, the surgeons of the 126th FST provided humanitarian surgical care to Afghan civilians. RESULTS: The FST surgeons provided 553 surgical evaluations on 511 Afghan civilians. Of the patients, 95% were male and 38% were children. Forty percent of the clinic visits involved wound care and 20% involved a general surgery diagnosis. Seventeen percent involved an orthopedic diagnosis and 23% involved various surgical subspecialty diagnoses. Of the patients, 11% required a procedure necessitating the use of anesthesia. Interviews with Afghan patients and civic leaders identified a positive impact. CONCLUSION: This is the first report of humanitarian surgical care provided by surgeons of a FST in Afghanistan. Time and resource investment was minimal with no evidence of a negative impact on the primary mission of the FST.

Bladder stones in Afghan children.

OBJECTIVES: Military surgeons have been providing humanitarian care in Afghanistan since 2002. There are scant published reports on the details of that care. We report here the experience of deployed U.S. Army general surgeons in the management of an endemic problem, bladder stones in Afghan children. METHODS: A retrospective review was performed of pediatric patients presenting to an International Security Assistance Force humanitarian clinic over a 12-month period from October 2010 to November 2011. Symptoms at presentation, diagnostic modalities, and treatment provided were analyzed. The general surgeons of the 126th Forward Surgical Team (FST) provided surgical consultations for this military humanitarian clinic on a remote base in western Afghanistan. RESULTS: Eight male pediatric patients of an average age of 4 years presented with dysuria and underwent further evaluation. In five patients, the use of a portable ultrasound machine led to the diagnosis of bladder stones. Three other patients presented with ultrasound exams from an Afghan clinic. Four patients underwent surgical removal of their bladder stones by the FST and 4 four patients, including one with a recurrent bladder stone, were referred to a distant Afghan Regional Hospital. No short-term complications occurred in the five patients available for follow-up. CONCLUSIONS: Military surgeons providing humanitarian care in rural areas of Afghanistan, and humanitarian surgeons serving in endemic areas, can expect to encounter multiple cases of bladder stones in pediatric patients. Dysuria is a typical presenting symptom. The FST has the resources to diagnose and treat this disorder. If accessible, Afghan regional hospitals can provide curative surgery.

Improving compliance with malaria chemoprophylaxis in Afghanistan.

OBJECTIVE: Historically, compliance with malaria chemoprophylaxis by military service members (MSM) has been notoriously low, ranging from 30 to 56%. Since 2002, 28 to 85 cases per year of malaria have occurred in MSM deployed to Afghanistan. During their deployment to Afghanistan, the authors identified a low compliance rate with malaria chemoprophylaxis. A performance improvement project was developed to improve compliance. METHODS: In July 2011, a performance improvement plan was developed to improve malaria chemoprophylaxis compliance in MSM arriving on a remote base in western Afghanistan. The plan included a 15-minute briefing and a medical consultation for MSM who had discontinued their chemoprophylaxis because of side effects. At the conclusion of their deployment, the MSM were surveyed on their compliance. RESULTS: Ninety-four MSM attended the briefings. Eighty (85%) MSM completed the survey in October 2011. Ninety-eight percent were taking doxycycline (n = 78). Ninety percent (n = 72) reported that they were compliant with their chemoprophylaxis. One entire unit (n = 29) was identified to be critically short of doxycycline, which initiated an emergency order for medication. Two noncompliant soldiers requested a consultation concerning side effects and were able to continue their chemoprophylaxis. CONCLUSION: Personalized in-theater briefings and consultations by knowledgeable providers may improve compliance with malaria chemoprophylaxis in MSM in Afghanistan.

Longterm followup assessment of a HER2/neu peptide (E75) vaccine for prevention of recurrence in high-risk prostate cancer patients.

BACKGROUND: E75 is an immunogenic peptide from the HER2/neu protein that is expressed in prostate cancer. High-risk prostate cancer (HRPC) patients demonstrating varying levels of HER2/neu expression were vaccinated with E75 peptide plus granulocyte-macrophage colony-stimulating factor to prevent postprostatectomy PSA and clinical recurrences. STUDY DESIGN: Forty evaluable HRPC patients were prospectively identified using the validated Center for Prostate Disease Research/CaPSURE high-risk equation and enrolled. HLA-A2(+) patients (n = 21) were vaccinated, and HLA-A2(-) patients (n = 19) were followed as clinical controls. All patients were assessed for clinicopathologic factors, biochemical recurrence (consecutive PSA value >or= 0.2 ng/mL), clinical recurrence, and survival. RESULTS: Comparing the vaccinated and control groups, there were no statistical differences in clinicopathologic prognostic factors. At a median followup of 58.2 months (range 18.8 to 62.7 months), PSA recurrence rates were not different between vaccinated (29%) and control (26%) groups. Median time to recurrence from operation was 14.0 months (range 5.7 to 53.4 months) versus 8.5 months (range 4.7 to 34.1 months) (p = 0.7), respectively. Three vaccinated patients had PSA recurrences during the vaccine series. If these patients were excluded, median time to recurrence for the vaccinated group extends to 42.7 months (range 20.4 to 53.4 months) (p = 0.4). Study-wide, only one clinical recurrence and death occurred in a vaccinated patient that was early in the vaccine series. Subset analysis comparing vaccinated recurrent patients with control recurrences noted some statistical trends. CONCLUSIONS: The HER2/neu (E75) vaccine can prevent or delay recurrences in HRPC patients if completed before PSA recurrence. A larger randomized phase II trial in HLA-A2(+) patients will be required to confirm these findings.

Combined clinical trial results of a HER2/neu (E75) vaccine for the prevention of recurrence in high-risk breast cancer patients: U.S. Military Cancer Institute Clinical Trials Group Study I-01 and I-02.

PURPOSE: E75 is an immunogenic peptide from the HER2/neu protein, which is overexpressed in many breast cancer patients. We have conducted two overlapping E75 vaccine trials to prevent recurrence in node-positive (NP) and node-negative (NN) breast cancer patients. EXPERIMENTAL DESIGN: E75 (HER2/neu 369-377) + granulocyte macrophage colony-stimulating factor was given intradermally to previously treated, disease-free NP breast cancer patients in a dose escalation safety trial and to NN breast cancer patients in a dose optimization study. Local and systemic toxicity was monitored. Immunologic responses were assessed using in vitro assays and in vivo delayed-type hypersensitivity responses. Clinical recurrences were documented. RESULTS: One hundred and eighty-six patients were enrolled in the two studies (NP, 95; NN, 91). Human leucocyte antigen A2 (HLA-A2) and HLA-A3 patients were vaccinated (n = 101), whereas all others (n = 85) were followed prospectively as controls. Toxicities were minimal, and a dose-dependent immunologic response to the vaccine was shown. Planned primary analysis revealed a recurrence rate of 5.6% in vaccinated patients compared with 14.2% in the controls (P = 0.04) at a median of 20 months follow-up. As vaccine-specific immunity waned over time, the difference in recurrence lost significance at 26 months median follow-up (8.3% versus 14.8%); however, a significant difference in the pattern of recurrence persisted. CONCLUSIONS: E75 is safe and effective in raising a dose-dependent HER2/neu immunity in HLA-A2 and HLA-A3 NP and NN breast cancer patients. More importantly, E75 may reduce recurrences in disease-free, conventionally treated, high-risk breast cancer patients. These findings warrant a prospective, randomized phase III trial of the E75 vaccine with periodic booster to prevent breast cancer recurrences.

Phase I clinical trial of a HER-2/neu peptide (E75) vaccine for the prevention of prostate-specific antigen recurrence in high-risk prostate cancer patients.

PURPOSE: The E75 peptide is an immunogenic peptide from the HER-2/neu protein that is substantially expressed in prostate cancer. We are conducting a clinical trial of an E75/granulocyte macrophage colony-stimulating factor vaccine to prevent post-prostatectomy prostate-specific antigen (PSA) recurrences in high-risk prostate cancer (HRPC) patients. EXPERIMENTAL DESIGN: Prostate cancer patients at high risk for recurrence were prospectively evaluated and identified by the validated Center for Prostate Disease Research (CPDR)/CaPSURE high-risk equation. From these high-risk equation patients, 27 HER-2/neu-expressing prostate cancer patients were enrolled. HLA-A2+ patients (n = 17) were vaccinated, whereas HLA-A2- patients (n = 10) were followed as clinical controls. Local/systemic toxicities, immunologic responses, and time to recurrence were measured. RESULTS: This vaccine is safe with only minor toxicities observed. Additionally, the vaccine is immunogenic with all patients showing both in vivo and in vitro phenotypic and functional immune responses, although variable. HLA-A2+ patients were found to have larger tumors, higher postoperative Gleason scores, and more high-risk CPDR scores than HLA-A2- patients. Despite these differences, disease-free survival was not different between the vaccinated HLA-A2+ patients and the HLA-A2- controls at a median follow up of 23 months. Three of the four vaccinated patients that recurred had rising PSAs at the initiation of the trial. Ex vivo phenotypic assays were predictive of recurrences and correlated in general with functional assays. CONCLUSIONS: The E75 vaccine strategy is safe and effective in eliciting an immune response against the HER-2/neu protein in HRPC patients and may be useful as a preventive strategy against disease recurrence. Vaccination in response to a rising PSA may be too late.

Preclinical testing of a peptide-based, HER2/neu vaccine for prostate cancer.

The HER2/neu protein is over-expressed in multiple epithelial tumors and the source of immunogenic peptides currently under investigation in vaccine trials in ovarian and breast cancers. We sought to define the correlation between HER2/neu expression and risk for prostate cancer recurrence and then determine the potential efficacy of anti-HER2/neu vaccination in prostate cancer patients at risk for recurrence. The risk for prostate-specific antigen (PSA) recurrence in 95 patients undergoing prostatectomy at the Walter Reed Army Medical Center (WRAMC) was calculated and correlated to HER2/neu expression, as determined by immunohistochemical staining. Peripheral blood lymphocytes (PBL) were then isolated from six consecutive human leukocyte antigen (HLA) A2+ patients with HER2/neu+ prostate tumors. These PBL were grown in parallel cultures and stimulated either with no peptide, HER2/neu E75 peptide, or control peptide. The cultures were compared for stimulated proliferation, induced peptide-specific cytotoxicity and tumor-specific cytotoxicity. When assessed by risk group, 69% of the high risk patients' tumors over-expressed HER2/neu compared to 47% of the intermediate risk group (p<0.05). Evaluation of the in vitro immune response of PBL isolated from six consecutive prostate cancer patients revealed a statistically significant increase in E75-stimulated lymphocytic proliferation. E75-stimulated lymphocytes demonstrated an E75-specific cytolytic response in 6/6 prostate cancer patients that increased with successive stimulations. Moreover, these E75-specific lymphocytes also demonstrated tumor-specific lysis against HER2/neu-expressing prostate cancer cell lines. The majority of prostate cancer patients at high risk for recurrence have HER2/neu expressing tumors. Hence, HER2/neu is a viable target for immunotherapeutics such as preventative immunization strategies with HER2/neu peptide vaccines.

Direct measurement of peptide-specific CD8+ T cells using HLA-A2:Ig dimer for monitoring the in vivo immune response to a HER2/neu vaccine in breast and prostate cancer patients.

HER2/neu is a proto-oncogene and a member of the epidermal growth factor receptor family of proteins that is overexpressed in numerous types of human cancer. We are currently conducting clinical trials with the HER2/neu E75 peptide vaccine in breast and prostate cancer patients. We have evaluated the use of HLA-A2 dimer molecule for the immunological monitoring of cancer patients receiving the E75 peptide vaccine. Peripheral blood samples from patients receiving the vaccine were stained with HLA-A2 dimers containing the vaccine peptide E75 or control peptides and analyzed by flow cytometry. We compared the HLA-A2 dimer assay to standard methods of immunologic monitoring (IFN-gamma release, lymphocyte proliferation, and cytotoxicity). The HLA-A2 dimer assay was also compared with the HLA-A2 tetramer assay. E75 peptide-specific CD8 T cells were detected directly in the peripheral blood of patients by staining with E75-HLA-A2 dimers and CD8 antibodies. T cell cultures generated by repeated stimulations using E75 peptide-pulsed dendritic cells showed increased staining with E75-peptide loaded HLA-A2 dimers. Simultaneously analysis by the dimer assay and standard immunologic assays demonstrated that the dimer-staining assay correlated well with these methods of immunologic monitoring. A direct comparison using E75-specific HLA-A2 tetramers and HLA-A2 dimers for the detection of E75-specific CD8 T cells in peripheral blood showed comparable results with the two assays. Our findings indicate that the HLA-A2 dimer is a powerful new tool for directly quantifying and monitoring immune responses of antigen-specific T cells in peptide vaccine clinical trials.