PuraStat in gastrointestinal bleeding: results of a prospective multicentre observational pilot study.

BACKGROUND: A recently developed haemostatic peptide gel for endoscopic application has been introduced to improve the management of gastrointestinal bleeding. The aim of this pilot study was to evaluate the feasibility, safety, efficacy and indication profiles of PuraStat in a clinical setting. METHODS: In this prospective observational multicentre pilot study, patients with acute non-variceal gastrointestinal bleeding (upper and lower) were included. Primary and secondary application of PuraStat was evaluated. Haemoglobin, prothrombin time, platelets and transfusion behaviour were documented before and after haemostasis. The efficacy of PuraStat was assessed during the procedure, at 3 days and 1 week after application. RESULTS: 111 patients with acute gastrointestinal bleeding were recruited into the study. 70 percent (78/111) of the patients had upper gastrointestinal bleeding and 30% (33/111) had lower gastrointestinal bleeding. After primary application of PuraStat, initial haemostatic success was achieved in 94% of patients (74/79, 95% CI 88-99%), and in 75% of the patients when used as a secondary haemostatic product, following failure of established techniques (24/32, 95% CI 59-91%). The therapeutic success rates (absence of rebleeding) after 3 and 7 days were 91% and 87% after primary use, and 87% and 81% in all study patients. Overall rebleeding rate at 30 day follow-up was 16% (18/111). In the 5 patients who finally required surgery (4.5%), PuraStat allowed temporary haemostasis and stabilisation. CONCLUSIONS: PuraStat expanded the therapeutic toolbox available for an effective treatment of gastrointestinal bleeding sources. It could be safely applied and administered without complications as a primary or secondary therapy. PuraStat may additionally serve as a bridge to surgery in order to achieve temporary haemostasis in case of refractory severe bleeding, possibly playing a role in preventing immediate emergency surgery.

Environmental health perceptions in a superfund community.

A disconnect between community perceptions and officially documented Superfund remedial actions and health outcomes may hinder the essential community engagement at Superfund sites. This study evaluates the extent of one such potential disconnect in Butte, Montana, which is part of the largest U.S. Superfund site in the U.S. Since the 1860s, when mining began in Butte, mine waste disposal practices in Butte and surrounding areas have left behind massive deposits that have contaminated the area's soil, sediment, groundwater and surface water with arsenic and heavy metals. Over the last four decades, a substantial amount of remediation work has been completed along with requisite community engagement and health studies at this Superfund site. The potential disconnect was evaluated using a new survey instrument that covered: (a) general environmental health perceptions, (b) mine-waste specific environmental health perceptions, (c) effectiveness of community engagement, (d) knowledge of health outcomes, and (e) demographics. The survey results demonstrated a disconnect in many instances where objective remedial improvements may not have resulted in improved environmental health perceptions in the community. The disconnect was most pronounced in the case of drinking water protection from mine waste and knowledge of health outcomes (cancer incidence rates and children's blood levels). The use of similar environmental health perception measurements may aid responsible agencies in monitoring for and addressing environmental health perception disconnects through better community engagement for the benefit of the impacted communities.

Noise characterization of oil and gas operations.

In cooperation with The Colorado Oil and Gas Conservation Commission, researchers at Colorado State University performed area noise monitoring at 23 oil and gas sites throughout Northern Colorado. The goals of this study were to: (1) measure and compare the noise levels for the different phases of oil and gas development sites; (2) evaluate the effectiveness of noise barriers; and (3) determine if noise levels exceeded the Colorado Oil and Gas Conservation Commission noise limits. The four phases of oil and gas development include drilling, hydraulic fracturing, completion and production. Noise measurements were collected using the A- and C-weighted sound scales. Octave band analysis was also performed to characterize the frequency spectra of the noise measurements. Noise measurements were collected using noise dosimeters and a hand-held sound-level meter at specified distances from the development sites in each cardinal direction. At 350 ft (107 m), drilling, hydraulic fracturing, and completion sites without noise barriers exceeded the maximum permissible noise levels for residential and commercial zones (55 dBA and 60 dBA, respectively). In addition, drilling and hydraulic fracturing sites with noise barriers exceeded the maximum permissible noise level for residential zones (55 dBA). However, during drilling, hydraulic fracturing, and completion operations, oil producers are allowed an exception to the noise permissible limits in that they only must comply with the industrial noise limit (80 dBA). It is stated in Rule 604.c.(2)A. that: "Operations involving pipeline or gas facility installation or maintenance, the use of a drilling rig, completion rig, workover rig, or stimulation is subject to the maximum permissible noise levels for industrial zones (80dBA)." [8] Production sites were within the Colorado Oil and Gas Conservation Commission permissible noise level criteria for all zones. At 350 ft (107 m) from the noise source, all drilling, hydraulic fracturing, and completion sites exceeded 65 dBC. Current noise wall mitigation strategies reduced noise levels in both the A- and C-weighted scale measurements. However, this reduction in noise was not sufficient to reduce the noise below the residential permissible noise level (55 dBA).

Developing effective worker health and safety training materials: hazard awareness, identification, recognition, and control for the salon industry.

OBJECTIVE: In addition to formaldehyde, workers in salons can be exposed to other chemical irritants, sensitizers, carcinogens, reproductive hazards, infectious agents, ergonomic, and other physical hazards. Worker health and safety training is challenging because of current product labeling practices and the myriad of hazards portending risk for a wide variety of health effects. METHODS: Through a Susan B. Harwood Targeted Topic Training grant from the Occupational Safety and Health Administration and assistance from salon development and training partners, we developed, delivered, and validated a health and safety training program using an iterative five-pronged approach. RESULTS: The training was well received and resulted in knowledge gain, improved workplace safety practices, and increased communication about health and safety. CONCLUSIONS: These training materials are available for download from the Occupational Safety and Health Administration's Susan B. Harwood Training Grant Program Web site.

Toxic megacolon.

Toxic megacolon represents a dreaded complication of mainly inflammatory or infectious conditions of the colon. It is most commonly associated with inflammatory bowel disease (IBD), i.e., ulcerative colitis or ileocolonic Crohn's disease. Lately, the epidemiology has shifted toward infectious causes, specifically due to an increase of Clostridium difficile-associated colitis possibly due to the extensive (ab)use of broad-spectrum antibiotics. Other important infectious etiologies include Salmonella, Shigella, Campylobacter, Cytomegalovirus (CMV), rotavirus, Aspergillus, and Entameba. Less frequently, toxic megacolon has been attributed to ischemic colitis, collagenous colitis, or obstructive colorectal cancer. Toxic colonic dilatation may also occur in hemolytic-uremic syndrome (HUS) caused by enterohemorrhagic or enteroaggregative Escherichia coli O157 (EHEC, EAEC, or EAHEC). The pathophysiological mechanisms leading to toxic colonic dilatation are incompletely understood. The main characteristics of toxic megacolon are signs of systemic toxicity and severe colonic distension. Diagnosis is made by clinical evaluation for systemic toxicity and imaging studies depicting colonic dilatation. Plain abdominal imaging is still the most established radiological instrument. However, computed tomography scanning and transabdominal intestinal ultrasound are promising alternatives that add additional information. Management of toxic megacolon is an interdisciplinary task that requires close interaction of gastroenterologists and surgeons from the very beginning. The optimal timing of surgery for toxic megacolon can be challenging. Here we review the latest data on the pathogenesis, clinical presentation, laboratory, and imaging modalities and provide algorithms for an evidence-based diagnostic and therapeutic approach.

Detection and functional analysis of tumor infiltrating T-lymphocytes (TIL) in liver metastases from colorectal cancer.

BACKGROUND: Tumor-infiltrating T lymphocytes (TIL) play an important role in primary colorectal cancer, but their activity in liver metastases has not yet been investigated. The aim of this study was to examine whether tumor-selective infiltration, activation, and cytotoxic activity of TIL can be demonstrated in situ in colorectal liver metastases. METHODS: TIL were obtained from liver metastases and corresponding normal liver tissue of 16 patients with colorectal liver metastases. Characterization of TIL in situ was performed by multicolor flowcytometric analysis. Presence of tumor antigen-reactive T cells was evaluated by interferon gamma Elispot analysis. RESULTS: TIL in colorectal liver metastases responding against tumor antigens were present in most patients. Although the proportions of CD3(+) T cells were comparable in liver metastasis and normal liver tissue, metastases contained significantly enhanced proportions of CD4(+) cells (49% vs. 22%, P < .001). Among all CD4(+) T helper cells, the proportion of activated (CD4(+)CD25(+)) effector cells was significantly increased in liver metastases (15.0% vs. 7.8%, P = .003). Metastases showed significantly higher proportions of activated (CD69(+) [70.1% vs. 49.8%, P = .02] and CD25(+) [4.1% vs. .6%, P = .06]) and cytotoxically active (CD107a(+)) CD8(+) TIL (3.2% vs. 1.3%, P = .03). Importantly, the presence of activated T helper cells correlated with the frequencies of cytotoxic T lymphocytes that exerted cytotoxic activity in situ (P = .02). CONCLUSION: CD4(+) and CD8(+) TIL are selectively activated in liver metastases, and cytotoxic T lymphocytes exert tumor-selective cytotoxic activity in situ in the presence of activated T helper cells, suggesting the requirement of in-situ-activated T helper cells for efficient cytotoxic T lymphocytes effector function.

Tumor infiltrating T lymphocytes in colorectal cancer: Tumor-selective activation and cytotoxic activity in situ.

OBJECTIVE: To examine whether tumor-selective infiltration, activation, and cytotoxic activity of tumor infiltrating T lymphocytes (TIL) can be demonstrated in situ in colorectal cancer samples. SUMMARY BACKGROUND DATA: Recent studies indicated a correlation between the presence of TIL and an improved prognosis in colorectal cancer. However, tumor-selective activation and cytotoxic activity of CD8 TIL in situ in colorectal cancer patients have not yet been examined. METHODS: Tumor samples from 49 patients and corresponding normal mucosa samples from 23 patients with colorectal cancer (UICC stages II-IV) were examined for TIL. Two-color fluorescence immunohistochemistry and multicolor flowcytometric (FACS) analysis were used for quantification of CD8 T cells and measurement of their activation status (CD69-expression) and cytotoxic activity (CD107a-expression) in situ. Presence of tumor antigen-reactive T cells in tumor, blood, and bone marrow was evaluated by IFN-gamma Elispot analysis. RESULTS: While absolute numbers of CD8 T cells were similar, CD4 T helper cells were significantly increased in tumor tissue compared with normal mucosa. There was a significantly higher proportion of activated and cytotoxically active CD8 TIL in colorectal cancer compared with normal mucosa. Increased activation, cytotoxic activity, and functional reactivity of TIL were correlated with the presence of functional tumor antigen-reactive T cells in the blood and bone marrow. The proportion of activated TIL decreased significantly with higher tumor stage. CONCLUSIONS: Tumor-selective activation and cytotoxic activity of CD8 TIL and tumor-selective migration of CD4 T helper cells were demonstrated in colorectal cancer for the first time. Our data support the immunogenicity of colorectal cancer and suggest clinical significance of tumor-specific immune responses.